Acinetobacter baumannii in food safety: emerging threats and control strategies

Abstract

Acinetobacter baumannii, a notorious multidrug-resistant (MDR) pathogen, is emerging as a critical concern in the food industry owing to its robust survival abilities and broad antibiotic resistance. Major concerns regarding A. baumannii include its increasing prevalence across diverse food products, its ability to form biofilms that enhance its persistence in food-processing environments, and its extensive antibiotic-resistance mechanisms, such as efflux pumps, which significantly reduce the efficacy of conventional sanitation and antimicrobial interventions. These factors also increase the risk of transmission of A. baumannii into the medical facilities. This review examines recent research on the survival and dissemination of A. baumannii within the food chain, and proposes novel surveillance and control strategies to mitigate its impact. Significant emphasis has been placed on innovative intervention strategies, including natural antimicrobials, biofilm-disrupting agents, and risk-management strategies. This review emphasizes the necessity for science-driven strategies to prevent A. baumannii from becoming a serious foodborne hazard.

Introduction

Acinetobacter baumannii is a gram-negative bacterium that is currently regarded as a globally significant multidrug-resistant (MDR) pathogen. It belongs to the notorious ESKAPE group of hospital-associated bacteria known for evading antibiotics (Kyriakidis et al., 2021; Thom et al., 2011), and infections caused by A. baumannii, such as ventilator-associated pneumonia, bacteremia, and wound infections, often have high mortality rates. Carbapenem-resistant A. baumannii is deemed a critical priority by the World Health Organization (WHO) for the development of new antibiotics (Tacconelli et al., 2018), underscoring the gravity of its resistance. It was primarily a concern in intensive care units and clinical settings. Individuals colonized by MDR organisms, particularly those with weakened immune systems, may subsequently develop severe infections or unwittingly serve as vectors for the introduction of these organisms into healthcare facilities. Historically, A. baumannii was not considered a typical foodborne pathogen. However, evidence has mounted in recent years that A. baumannii can contaminate food material and food-processing environments, raising concerns about a potential community reservoir and transmission route outside hospitals (Lupo et al., 2014; USDA, n.d.). Indeed, this organism has been isolated from a wide range of food products and sources, including fresh vegetables, dairy products, seafood, and raw meat, in multiple regions, sometimes at alarmingly high frequencies (Ababneh et al., 2022). For example, a study found A. baumannii group in approximately 11% of lettuce and fruit samples in Portugal (Carvalheira et al., 2017), and another study reported that approximately 7% of fresh produce samples in the Middle East were contaminated with A. baumannii, with several isolates being extensively drug resistant (Ababneh et al., 2022). Being ubiquitous in soil and water, A. baumannii can enter the food chain at various points from farm environments, such as irrigation water, manure, or contact with animal feces to processing facilities. It can survive on food products or contact surfaces owing to its formidable biofilm-forming ability (Ababneh et al., 2022; Dahiru and Enabulele, 2015). Furthrmore, some foodborne isolates have shown resistance profiles and genotypes identical to those of clinical epidemic clones (Hamze et al., 2025), suggesting that strains circulating in the food sector could seed difficult-to-treat infections in hospitals. A notable example is the identification of the colistin-resistance gene mcr-4.3 on plasmids in A. baumannii isolated from imported retail meat, which exhibited high similarity to plasmids found in clinical A. baumannii isolates, suggesting a potential role of the food chain in the global dissemination of this critical resistance gene (Bitar et al., 2019).

The growing food-safety concerns around A. baumannii in stem largely from its capacity to persist and spread under conditions that would eliminate many other bacteria. This organism tolerates desiccation and nutrient limitation, remains viable on surfaces for months, and can withstand certain food-grade disinfectants, such as chlorhexidine and quaternary ammonium compounds, at concentrations that normally inhibit other pathogens (Gallego, 2016). This means that standard sanitation protocols in food-processing plants may fail to eradicate A. baumannii once it has established a niche, such as in a biofilm on equipment or poorly accessible crevices. Moreover, the intrinsic and acquired resistance mechanisms of A. baumannii, including β-lactamases, efflux pumps, and target site modifications, significantly constrain antibiotic treatment options for human infections and pose challenges for the effective use of conventional antimicrobial preservatives in food systems (Kyriakidis et al., 2021). Therefore, contamination of food supply with A. baumannii represents an insidious public health threat. A. baumannii can colonize consumers without causing immediate symptoms, silently disseminating among communities or transferring resistance genes to other gut flora (Balázs et al., 2022). Consequently, there is a growing recognition of A. baumannii as an emerging foodborne hazard that warrants urgent attention within the framework of food safety and public health. This review summarizes current knowledge on the occurrence, survival mechanisms, and resistance traits of A. baumannii in food-related environments. Furthermore, innovative approaches, such as natural antimicrobials, and biofilm-disrupting agents, are explored for controlling this pathogen. By integrating insights from microbiology, food science, and public health, this review seeks to inform the knowledges on food contamination, antibiotic resistances, and biofilm formation of Acinetobacter strains and their control strategies forcused on natural compound- and artificial intelligence-based control strategies to limit the emergence and spread of A. baumannii through the food chain.

Food contamination by A. baumannii

Food contamination

A. baumannii has been isolated from a wide range of food products, indicating diverse potential sources of contamination. A study conducted in Portugal reported the presence of Acinetobacter spp. in 77.9% of lettuce and fruit samples, with approximately 11% of the isolates classified as A. baumannii (Carvalheira et al., 2017). These bacteria have occasionally been detected as endophytes in plant tissues, suggesting that fresh produce may act as a vehicle for A. baumannii beyond surface-level contamination (Carvalheira et al., 2017). Animal-derived foods are also implicated as potential avenues of Acinetobacter contamination. Furthermore, A. baumannii strains isolated from raw meat often carry multiple antibiotic-resistance and virulence genes, indicating that food animals may serve as reservoirs of MDR strains (Askari et al., 2019). Acinetobacter, including pathogenic strains, have been detected in raw meat and poultry products (Mari-Almirall et al., 2019). Dairy products also have been found to have Acinetobacter contamination. Various studies have reported the presence of these organisms in bovine and goat milk and cheese (Gurung et al., 2013; Ramos and Nascimento, 2019). A. baumannii was also recovered from fish and shrimp in market surveys, revealing seafood as a potential source (USDA). The detection of A. baumannii in various food products suggests its widespread presence throughout the food supply chain, presumably derived from environmental reservoirs, such as soil and water, and introduced via inadequate hygiene or cross-contamination during handling. For example, contaminated irrigation water or manure can introduce A. baumannii into produce, whereas poor hygiene in slaughterhouses and dairies may lead to the introduction of the bacterium into meat and milk. In addition, food products may contaminate new environments such as domestic kitchens (Amorim and Nascimento, 2017). Although the levels of A. baumannii in foods are generally lower than those of conventional foodborne pathogens, the possibility that even a small proportion of these isolates may exhibit multidrug resistance (MDR) remains a significant public health concern (Carvalheira et al., 2021). Thus, food products may serve as carriers of hospital-associated bacterial strains into the community. Therefore, A. baumannii needs to be considered as a potential food safety threat, rather than restricting its relevance to hospital-associated infections. Proactive measures to limit the presence of A. baumannii in the food supply chain may play a critical role in reducing the overall burden of this pathogen in both community and healthcare settings.

Genetic similarity among isolates from food and clinical samples

Comparative genomic analyses have provided an understanding of the genetic relatedness between foodborne and clinical strains of A. baumannii. Notably, some A. baumannii isolates recovered from retail food products were nearly genetically identical to strains associated with human infections. A recent whole-genome analysis of 70 A. baumannii isolates from raw meat in Europe revealed high genetic diversity and identified 49 sequence types. Notably, some meat-associated strains exhibited close core genome similarity to clinical MDR lineages, including the international clonal complexes IC11 and CC33 (Hamze et al., 2025). These food-derived isolates possessed the same carbapenem-resistance genes as those identified in clinical strains (Hamze et al., 2025). These findings suggest that virulent drug-resistant clones of A. baumannii are not restricted to clinical settings but may also disseminate through the food chain. In a study conducted in the Czech Republic that isolated colistin-resistant A. baumannii from imported frozen turkey livers, the plasmid harboring the mcr-4.3 colistin-resistance gene was found to be nearly identical to a plasmid identified in a clinical A. baumannii strain, suggesting a common origin or recent horizontal gene transfer between foodborne and clinical isolates (Bitar et al., 2019). Genomic evidence such as shared resistance genes and clonal similarity supports the view that foodborne and clinical A. baumannii strains are not entirely distinct. This raises the possibility that MDR strains may be transmitted to humans through food materials. In future, expanded genomic surveillance of A. baumannii from food, environmental, and clinical sources will be essential for mapping transmission pathways and evaluating the extent to which food-derived isolates are related to known epidemic clones. Preliminary findings revealed substantial genetic overlap, underscoring the importance of considering foodborne routes in the epidemiology of A. baumannii infections (Hamze et al., 2025).

Mechanisms of antibiotic resistance

Key resistance genes in A. baumannii

A. baumannii is resistant to a broad-spectrum of antibiotics, primarily due to a diverse array of acquired resistance genes, particularly those encoding antibiotic-modifying enzymes (Fig. 1). β-lactamase genes act as crucial determinants of resistance to β-lactam antibiotics, such as penicillins, cephalosporins, and carbapenems. A. baumannii is known to harbor a diverse array of carbapenem-hydrolyzing class D β-lactamases (CHDLs), classified as OXA-type enzymes. OXA-type β-lactamases, categorized as class D β-lactamases, are major contributors to the high-level resistance of A. baumannii to β-lactam antibiotics, particularly carbapenems. These enzymes exist in both intrinsic and acquired forms, significantly complicating the treatment of infections and exacerbating nosocomial outbreaks on a global scale. Among these, the intrinsic blaOXA-51-like gene is consistently found in nearly all A. baumannii isolates and is widely used as a molecular marker for species identification. Additionally, several acquired OXA-type carbapenemase genes, such as blaOXA-23, blaOXA-24, blaOXA-58, blaOXA-143, and blaOXA-235, have been reported, which play major roles in carbapenem resistance (Wong et al., 2019). Of these, OXA-23, which is frequently encoded in plasmids, is one of the most widespread carbapenemases in clinical A. baumannii isolates. Additionally, A. baumannii has acquired metallo-β-lactamases like NDM-1, VIM, and IMP that can hydrolyze carbapenems and other β-lactams (Perez et al., 2007). The blaNDM-1 gene has been identified in A. baumannii isolates across various countries and confers resistance against nearly all β-lactam antibiotics, except monobactams. These resistance genes are often located on mobile genetic elements such as plasmids and transposons that facilitate their spread. The insertion sequence ISAba1 is frequently found upstream of OXA β-lactamase genes in A. baumannii acting as a strong promoter that upregulates gene expression (Hamidian and Hall, 2013; Heritier et al., 2006). The insertion of ISAba1 upstream of either OXA-23 or the intrinsic OXA-51 gene markedly enhances their transcriptional activity, thereby contributing to high-level carbapenem resistance (Heritier et al., 2006). A. baumannii harbors a diverse set of resistance mechanisms, including aminoglycoside-modifying enzyme genes, such as aph, aad, and str; point mutations in the gyrA and parC genes that mediate fluoroquinolone resistance (Fig. 1); resistance genes against sulfonamides and trimethoprim that disrupt folate biosynthesis; and the overexpression of multidrug efflux pumps, including AdeABC and AdeIJK (Fig. 1). These resistance genes have contributed to the emergence of MDR and extensively drug-resistant (XDR) A. baumannii isolates that are resistant to nearly all clinically available antibiotics (Kyriakidis et al., 2021). A. baumannii strains harboring both blaOXA-23 and blaNDM-1 are largely non-susceptible to β-lactam antibiotics and frequently carry additional resistance determinants, such as tetB for tetracyclines, macrolide-resistance genes, and colistin-resistance mechanisms including mprF mutations or mobilized colistin-resistance mcr genes (Okdah et al., 2022; Wareth et al., 2021). The identification of these genes in food-derived A. baumannii isolates underscores a significant public health concern, as individuals exposed to such strains via food consumption may subsequently develop infections that are difficult to manage because of limited treatment options.

Fig. 1.

Schematic representation of antibiotic-resistance mechanisms in Acinetobacter baumannii. (1) AdeABC efflux pump expels antibiotics, (2) porin loss/modification limits drug entry, (3) β-lactamases inactivate β-lactams, (4) aminoglycoside-modifying enzymes and 30S rRNA methylation reduce aminoglycoside binding, (5) topoisomerase IV/DNA gyrase mutations lower fluoroquinolone affinity, (6) altered Modification of penicillin-binding proteins (PBPs) reduce β-lactam binding, (7) LPS modification decreases colistin binding, (8) capsule provides stress resistance and anti-phagocytic protection, and (9) biofilm formation enhances antimicrobial tolerance. (Kyriakidis et al., 2021; Roy et al., 2022)

Horizontal gene transfer of antibiotic resistance genes

Acinetobacter baumannii demonstrates both intrinsic resistance to antibiotics and the capacity to acquire new resistance genes via horizontal gene transfer (HGT). This organism exhibits remarkable genomic plasticity, enabling it to acquire foreign genetic material and incorporate it into its genome via transformation, conjugation, or transduction. Clinical isolates of A. baumannii frequently harbor plasmids, transposons, and integrons enriched with resistance genes, underscoring the critical role of HGT in the development of its MDR phenotype (Kyriakidis et al., 2021). Insertion sequence elements such as ISAba1 and ISAba125 facilitate the mobilization of resistance genes, including blaOXA-23 and blaNDM-1, between plasmids and the chromosome, enabling the rapid spread of these genes across strains (Blair et al., 2015). The ability of A. baumannii to acquire and express foreign resistance determinants plays a pivotal role in its evolution into a superbug (Mancuso et al., 2023; Wang et al., 2022). Notably, reservoirs of carbapenemase-producing A. baumannii have been identified beyond clinical settings, including in companion animals and wild birds such as pigeons, suggesting that HGT of resistance genes also occurs in the broader environment (Anyanwu et al., 2023; Dandachi et al., 2018). The high capacity of the bacterium for horizontal gene exchange suggests that any environment in which A. baumannii persists, such as soil or water contaminated with hospital waste or biofilms within food-processing facilities, may serve as a reservoir for the dissemination and recombination of antibiotic-resistance genes.

Particularly, food-associated environments may serve not only as reservoirs but also as active exchange platforms where HGT facilitates the emergence of more resistant and potentially virulent strains (Michaelis and Grohmann, 2023). Recent findings reinforce this notion by demonstrating the transfer of blaNDM variants among diverse bacterial strains in live poultry markets via environmental and food-based routes (Yin et al., 2024). Biofilms may provide conditions conducive for HGT. The coexistence of A. baumannii with other microbial species within biofilms in food-processing environments may facilitate HGT, potentially enabling the acquisition of novel plasmids carrying antimicrobial-resistance or virulence-associated genes.

Potential risks of foodborne transmission of antibiotic resistant strains

The presence of MDR A. baumannii in food sources represents a significant public health concern, as it suggests the potential for foodborne transmission of these highly drug-resistant pathogens. Although A. baumannii is not a typical conventional foodborne pathogen, its ability to colonize hosts and cause opportunistic infections remains a critical concern. Contaminated food may serve as a vector for the introduction of A. baumannii into the gastrointestinal tract or onto mucosal surfaces, such as the skin and oropharynx, particularly among immunocompromised individuals or those with indwelling medical devices. Several lines of evidence support this concern. For example, several studies have demonstrated that A. baumannii strains isolated from food products and those recovered from clinical settings often belong to identical or closely related clonal lineages and frequently exhibit comparable antimicrobial-resistance profiles (Bitar et al., 2019; Hamze et al., 2025).

Although the documented incidence of confirmed foodborne infections caused by Acinetobacter spp. remains low, the greater concern lies in their potential to colonize individuals without causing notable symptoms, thereby making those individuals asymptomatic carriers, thus enabling widespread environmental dissemination. Colonized individuals, including asymptomatic carriers, may serve as vectors for hospital introduction through hospitalization. Or, contaminated food can be brought in hospitals by visitors or food suppliers, then consumed by hospital patients (Malta et al., 2020). Once introduced into healthcare settings, these antibiotic-resistant strains can be disseminated through patient-to-patient transmission and thrive under selective pressure exerted by extensive antibiotic use. Of particular concern is the potential for nosocomial outbreaks in immunocompromised patients. Another potential risk is that the food may serve as a reservoir for A. baumannii to acquire additional antimicrobial-resistance traits.

Globalization of the food supply chain facilitates international dissemination of antimicrobial-resistant A. baumannii strains originating from contaminated produce or meat. A notable example is the detection of colistin-resistant A. baumannii harboring the mcr-4.3 gene in imported turkey livers, illustrating how international food trade can introduce clinically significant resistance determinants into regions where they were previously unreported (Bitar et al., 2019). Once such resistance genes are introduced into local bacterial communities under clinical or environmental conditions, they are notoriously difficult to eliminate because of their potential for stable integration and horizontal dissemination.

Environmental persistence, biofilm formation and pathogenicity mechanisms

Biofilm formation by A. baumannii significantly contributes to its persistence in both clinical and food-related environments. This bacterium can form robust, high-biomass biofilms on various abiotic surfaces, including stainless steel, polystyrene, and polycarbonate (Greene et al., 2016) (Fig. 2). Considering that stainless steel is widely used in food-associated surfaces such as conveyor belts, storage tanks, and cutting equipment, that come in contact with food during processing, the presence of A. baumannii biofilms on these surfaces can serve as persistent sources of contamination.

Fig. 2.

Biofilm development stages of Acinetobacter baumannii. a Biofilm development in A. baumannii occurs in five stages: (1) motility toward the surface, (2) reversible initial adhesion, (3) irreversible attachment and maturation with cell–cell interactions, (4) dispersion of cells from the mature biofilm, and (5) propagation initiating new biofilm cycles. b Key biofilm-associated virulence factors include Csu pili (abiotic adhesion), AbOmpA (biotic adhesion), Bap (biofilm stabilization), and BfmRS (regulation of biofilm-related genes). (Mendes et al., 2023; Wong et al., 2021)

Within a biofilm, cells are embedded in a self-produced extracellular polymeric matrix that provides protection against cleaning and disinfection. Acinetobacter biofilms are particularly difficult to eradicate and can persist on equipment surfaces despite routine sanitization procedures. A. baumannii isolates capable of biofilm formation are likely to exhibit increased tolerance to sanitizing agents (Fernandes et al., 2022). The biofilm matrix can impede the penetration of disinfectants, and the dense cellular community within the biofilm may facilitate the transfer of resistance genes, indicating that biofilm-forming isolates are often MDR strains (Fernandes et al., 2022; Malta et al., 2020). A. baumannii in a biofilm state demonstrates markedly enhanced tolerance and survival following exposure to quaternary ammonium or chlorine-based disinfectants at concentrations that are typically lethal to planktonic cells (Betchen et al., 2022). This resilience indicates that standard cleaning protocols may be insufficient, necessitating the implementation of enhanced sanitation measures against A. baumannii. Several studies have demonstrated that A. baumannii can form biofilms on the surfaces of fresh produce, such as leafy greens and fruits, although these biofilm structures are generally less mature and structurally underdeveloped. Nonetheless, even low levels of biofilm formation on fresh produce or within processing lines may enable A. baumannii to withstand standard washing procedures (Betchen et al., 2022). In food-processing environments, biofilms that develop on drains, floors, or equipment surfaces may serve as persistent sources of contamination, resulting in repeated introduction of A. baumannii into food products (Fig. 2). Therefore, the biofilm-forming capacity of A. baumannii represents a key survival strategy in food-production environments. Effective control measures must target not only planktonic cells but also those embedded within biofilms.

Regulation of biofilm-associated genes (bap, ompA, etc.)

A. baumannii biofilm formation involves a set of genes encoding adherence factors and biofilm matrix components (Fig. 2). Among these, biofilm-associated protein (Bap) has been identified as a key determinant because of its critical role in surface attachment and biofilm maturation (Fallah et al., 2017) (Fig. 2). The bap gene encodes a large cell-surface protein, functionally similar to Bap in Staphylococcus aureus. Experimental studies have demonstrated that Bap is essential for the development of mature, three-dimensional biofilm architectures characterized by tower-like structures and water channel formation (Brossard and Campagnari, 2012). Mutants lacking Bap exhibit significantly thinner and disorganized biofilms, highlighting the essential role of the protein in maintaining biofilm architecture and structural cohesion. Furthermore, Bap has been implicated in epithelial cell adhesion and identified as a mediator of A. baumannii attachment to human bronchial epithelial cells and keratinocytes. This adhesion represents a critical initial step in host colonization and infection; however, Bap is not required for the subsequent invasion of host cells (Brossard and Campagnari, 2012). The presence of Bap on bacterial cell surfaces has also been shown to increase cell-surface hydrophobicity, thereby promoting enhanced interactions with abiotic substrates and host tissues. Therefore, Bap plays a dual role, promoting environmental persistence through surface-associated biofilm formation and enhancing pathogenicity by facilitating host colonization.

Another major adhesin is the outer membrane protein A (OmpA), which is among the most abundant outer membrane proteins in A. baumannii and exhibits multiple functions (Fig. 2). In addition to serving as a porin, OmpA contributes significantly to biofilm formation and facilitates both the adherence to and invasion of host cells. OmpA has been identified as a prominent virulence factor involved in adhesion, and studies have demonstrated that antibodies targeting OmpA can inhibit A. baumannii attachment to epithelial cells and impair biofilm formation (Brossard and Campagnari, 2012). OmpA mediates binding to receptors on host cells, including the surface molecules of epithelial cells, and under specific conditions, it has been shown to translocate to the host cell nucleus, where it induces cytotoxic effects. Within biofilms, OmpA facilitates bacterial adhesion to abiotic surfaces, such as plastics commonly found in medical devices, and food packaging materials (Rafiei Delfan et al., 2024). OmpA has also been implicated in maintaining biofilm stability. Overall, Bap and OmpA are two major biofilm-associated proteins that enhance the adhesive and aggregation properties of A. baumannii, thereby promoting its persistence on abiotic surfaces and facilitating its interactions with host tissues (Zarrilli, 2016).

Expression of biofilm-associated genes in A. baumannii is governed by a complex regulatory network. One well-characterized system is BfmRS, a two-component signal transduction system (TCS) that mediates responses to environmental stimuli (Fig. 2). BfmRS is widely recognized as a master regulator of biofilm formation, because bfmR mutants exhibit a marked deficiency in the development of mature biofilm structures (Tomaras et al., 2008). BfmR, the response regulator of the BfmRS two-component system, directly regulates the csuA/BABCDE operon, which encodes the Csu fimbriae (chaperone-usher pili) that is involved in surface attachment and pellicle formation during the early stages of biofilm development (Chen et al., 2024; Tomaras et al., 2008) (Fig. 2). Under specific environmental conditions, phosphorylated BfmR activates the expression of genes involved in pili production, thereby initiating the early stages of biofilm formation.

Another regulator, AdeRS, which governs the expression of the AdeABC efflux pump, has been implicated in the modulation of biofilm development, suggesting regulatory interplay between antimicrobial resistance and biofilm-associated pathways (Richmond et al., 2016) (Fig. 1). Global regulatory systems such as quorum sensing (QS) are also believed to contribute to biofilm regulation in A. baumannii. The AbaI/AbaR QS system produces acyl-homoserine lactones (AHLs), and QS signaling has been shown to influence biofilm maturation, thickness, and dispersal (Mayer et al., 2020). Additionally, the ferric uptake regulator (Fur) serves as a molecular link between iron availability and the regulation of biofilm-associated genes. Multiple stress response regulators have also been implicated in the modulation of biofilm formation under environmental stress conditions (Zhang et al., 2025). Recently identified regulatory elements include a small RNA that influences the expression of biofilm-related genes and a blue-light sensing system (BlsA) that differentially regulates motility and biofilm formation in response to light exposure (Tuttobene et al., 2021). In summary, biofilm formation in A. baumannii is a tightly regulated and multifactorial process involving key structural elements, such as bap, ompA, and csu pili, coordinated by complex regulatory networks that respond to diverse environmental signals (Zarrilli, 2016). Disruption of these regulatory pathways through various means, such as bap deletion or BfmR inactivation, significantly impairs the capacity of A. baumannii to form biofilms and persist on abiotic surfaces (Longo et al., 2014), which is why these factors are attractive targets for antivirulence strategies.

Environmental factors affecting biofilm formation

Environmental conditions play a critical role in modulating biofilm development of A. baumannii and its survival within biofilm communities. Among these, oxidative stress is particularly significant. Within host environments and certain food processing settings, A. baumannii may encounter reactive oxygen species (ROS), such as hydrogen peroxide (H₂O₂) and superoxide radicals (Sun et al., 2016). Acinetobacter baumannii is capable of sensing oxidative stress and initiating protective responses closely linked to biofilm physiology. Under oxidative conditions, the bacterium upregulates various antioxidant and stress-related enzymes, including catalases such as KatE, peroxidases, superoxide dismutases, and components of the DNA repair machinery (Ajiboye et al., 2018; Juttukonda et al., 2019; Sun et al., 2016). Proteomic analyses have demonstrated that A. baumannii cells in the stationary phase or during biofilm growth exhibit increased expression of enzymes involved in oxidative stress defense, including alkyl hydroperoxide reductase and other oxidoreductases, that contribute to the eradication of ROS. This response not only enhances the survival of individual cells under oxidative stress but may also contribute to collective resistance within the biofilm matrix, where ROS can be neutralized by extracellular matrix components and shared enzymatic activity (Cabral et al., 2011; Soares et al., 2010). Several studies have suggested that mild oxidative stress paradoxically induces biofilm formation in A. baumannii. It has been hypothesized that sublethal oxidative stress acts as a signal that prompts the bacteria to transition to a biofilm-associated state. In contrast, the removal of oxidative stress signals through the application of antioxidants has been associated with reduced biofilm formation, presumably owing to the lack of environmental stimuli that trigger biofilm formation (Nucleo et al., 2009).

In addition to oxidative stress, iron limitation is a significant environmental factor that influences A. baumannii physiology and biofilm development. Iron is essential for bacterial proliferation and the activity of biofilm-associated enzymes. Under iron-restricted conditions, A. baumannii markedly upregulates siderophore biosynthesis along with other iron-acquisition systems, leading to notable physiological adaptations as a bacterial stress response. Several studies have investigated the effects of iron chelation on biofilm formation; however, the outcomes appear to be strain-dependent. Iron deprivation does not consistently promote biofilm formation in many A. baumannii isolates; under specific conditions, iron supplementation has been observed to enhance biofilm production potentially due to increased growth capacity (Gentile et al., 2014). These findings suggest that iron availability modulates biofilm formation in A. baumannii through complex, strain-dependent mechanisms. Overall, iron metabolism is closely associated with global regulatory pathways, particularly the Fur regulatory system, which controls the expression of numerous genes involved in both biofilm development and virulence (Bisaro et al., 2023).

Temperature is another environmental factor influencing biofilm formation in A. baumannii. For certain strains, biofilm production is maximized at approximately 30 °C and significantly reduced at 37 °C, suggesting that the biofilm formation in A. baumannii is dependent on temperature (Eze and El Zowalaty, 2019; Kazemi et al., 2011). Salinity and osmotic stresses are other important environmental factors influencing A. baumannii physiology. As a genus that includes marine-associated species, Acinetobacter displays a degree of salt tolerance. However, exposure to high salinity or desiccation induces physiological stress that may trigger biofilm formation as a protective adaptation. Similarly, nutrient limitation significantly alters cellular physiology. Under nutrient-deprived conditions, A. baumannii transitions to the stationary phase and activates stress-response pathways. During this phase, proteins involved in energy metabolism are downregulated, whereas stress-related proteins, including molecular chaperones, such as GroEL and DNA maintenance enzymes, are upregulated to enhance survival under unfavorable conditions (Breisch et al., 2022; Soares et al., 2010; Zeidler and Muller, 2019). Biofilm maturation is commonly associated with nutrient limitation, particularly in the inner regions of the biofilm where resource diffusion is restricted. Acinetobacter baumannii demonstrates a notable ability to persist under such nutrient-deprived conditions, which supports its survival within biofilm communities. In addition to nutritional stress, A. baumannii also responds differently to certain chemicals. Although 70% ethanol is lethal to many bacterial species, A. baumannii can tolerate lower concentrations of ethanol and may exploit such exposures to enhance its pathogenic potential (Chiang et al., 2018). Ethanol may act not only as a carbon source, but also as a signaling molecule that induces the expression of virulence-associated genes in A. baumannii (Nwugo et al., 2012). These observations suggest that residual ethanol from sanitizers may be metabolized by A. baumannii and serve as a cue to upregulate the production of virulence-associated factors, such as biofilm components or toxins. Although this phenomenon remains under investigation, it highlights the remarkable adaptability of A. baumannii to environmental stressors.

In summary, A. baumannii has evolved to survive in adverse conditions via a range of adaptive mechanisms. Biofilm formation constitutes a primary survival strategy that enables the organism to persist in a surface-attached state within a self-produced extracellular matrix. Within biofilms, nutrient and oxygen gradients give rise to spatially distinct microenvironments that promote metabolic adaptation in A. baumannii. In oxygen-depleted zones, cells often shift toward fermentative metabolism and adopt low-energy dormant states that provide increased tolerance to antimicrobial agents (Stewart et al., 2019; Yeom et al., 2013). Exposure to oxidative stress and other stressors induces a protective state in A. baumannii, which allows a subset of the population to survive under hostile conditions. These adaptations enhance environmental resilience, thereby hindering eradication efforts. These adaptations may also indirectly contribute to virulence by maintaining stress-tolerant cells capable of initiating infection when a susceptible host is encountered. Targeting stress-response pathways is a promising approach to control A. baumannii persistence. Potential strategies include the use of pro-oxidants to disrupt antioxidant defenses. These interventions may help reduce A. baumannii survival in food-related and clinical environments, ultimately lowering the risk of transmission and infection.

Environmental survival through siderophore-mediated iron acquisition

Iron is indispensable for core metabolic functions including DNA replication, respiration, and oxidative stress defense. Iron acquisition is a critical virulence factor of A. baumannii. Free iron is extremely scarce in the human body as it is tightly bound by host proteins such as transferrin, lactoferrin, ferritin, and heme. Iron is an essential nutrient for the survival and proliferation of A. baumannii. Therefore, for infection to progress, it is necessary for A. baumannii to acquire iron from the iron-limited host environment (Cook-Libin et al., 2022; Wooldridge and Williams, 1993). To adapt to iron-restricted conditions, A. baumannii uses specialized iron-scavenging systems primarily through the secretion of siderophores (Fig. 3). These high-affinity chelators bind Fe³⁺ from host tissues or the environment and facilitate its uptake into the cells. The principal siderophore produced by A. baumannii is acinetobactin, a catechol–hydroxamate compound with strong iron-binding affinity (Fig. 3). After chelation, the acinetobactin–iron complex is recognized by specific outer membrane receptors and actively transported into the bacterium. Some strains also produce an additional siderophore, baumannoferrin, which may further enhance iron acquisition (Bohac et al., 2019; Sheldon and Skaar, 2020).

Fig. 3.

Virulence strategies of Acinetobacter baumannii. A. baumannii employs multiple virulence mechanisms to persist in the host environment. These include high-affinity iron acquisition via siderophores (acinetobactin and baumannoferrin), delivery of toxins and enzymes through outer membrane vesicles (OMVs), and immune evasion via polysaccharide capsule formation. Surface adhesins, such as OmpA, Bap, and Ata, promote adherence to host tissues and abiotic surfaces, contributing to both colonization and biofilm formation. RTX toxins promote host cell lysis and inflammation through pore formation in the membrane. PilY1, located at the tip of Type IV pili, facilitates adhesion to host cells and abiotic surfaces, supporting initial colonization and biofilm formation. LipA, a secreted lipase, degrades host lipids for nutrient acquisition and modulates surface hydrophobicity, enhancing attachment and survival. Phospholipase D (PLD) disrupts host phospholipid membranes, promoting tissue invasion, intracellular entry, and immune evasion. Collectively, these factors enable tissue damage, immune resistance, and nutrient acquisition, strengthening the ability of A. baumannii as a formidable opportunistic pathogen (Eze et al., 2018; Morris et al., 2019)

The role of siderophores in A. baumannii pathogenicity has been revealed through mutant analyses, in which the disruption of acinetobactin biosynthesis or transport genes in the reference strain ATCC 19606 resulted in severely impaired growth under iron-limited conditions and substantially diminished virulence in infection systems (Dorsey et al., 2004; Gaddy et al., 2012; Yamamoto et al., 1994). Acinetobactin-deficient mutants exhibit impaired intracellular replication in host epithelial cells and display reduced virulence in both Galleria mellonella and murine infection systems (Gaddy et al., 2012). In the absence of siderophores, A. baumannii is unable to obtain sufficient iron within the iron-restricted environment of the host, which compromises its capacity to sustain the infection. To limit bacterial growth, the host employs a strategy known as nutritional immunity, whereby iron is tightly sequestered by host proteins. Siderophore production enables A. baumannii to overcome this defense mechanism by scavenging iron from host sources, thereby supporting its survival and pathogenicity (Penwell et al., 2012; Sheldon and Skaar, 2020). Although siderophores primarily secure iron for bacterial survival, their activity may also contribute to host damage. The depletion of extracellular iron by siderophores can impair essential host cell functions and induce inflammatory responses. Furthermore, emerging evidence suggests that acinetobactin exerts direct cytotoxic effects on host cells, independent of its iron-chelating role (Cook-Libin et al., 2022). These observations highlight the dual function of siderophores as nutrient acquisition tools and potential virulence factors.

In food-associated environments, siderophore production may contribute to the persistence of A. baumannii, particularly in iron-limited matrices, such as plant-based foods and dairy products, where free iron is scarce or tightly bound. If A. baumannii enters the human body via contaminated food, siderophores are essential for facilitating the initial colonization under host-imposed iron restriction. Notably, some strains are also capable of utilizing xenosiderophores, which are iron-chelating compounds produced by other microorganisms, demonstrating their metabolic flexibility in iron acquisition across diverse environments (Funahashi et al., 2012; Sheldon and Skaar, 2020). Iron availability also influences a wide range of virulence and metabolic regulation in A. baumannii. The ferric uptake regulator (Fur) represses siderophore biosynthesis genes under iron-replete conditions. However, during iron limitation, Fur repression is relieved, leading not only to upregulation of siderophore pathways but also to widespread transcriptional changes. Transcriptomic analyses have shown that more than 1200 genes respond to iron availability, indicating that iron acts as a global regulatory signal affecting diverse aspects of bacterial physiology and pathogenicity (Eijkelkamp et al., 2011). A substantial proportion of these iron-responsive genes has been implicated in virulence and core metabolic functions. For example, iron-regulated genes encode for outer membrane proteins, biofilm-associated factors, and potential elements of quorum sensing systems. These observations suggest that iron availability functions not only as a nutritional signal but also as a regulatory signal through which A. baumannii modulates its pathogenic potential (Eijkelkamp et al., 2011; Modarresi et al., 2015).

Siderophore-dependent iron acquisition is an important therapeutic target because it is essential for the survival and virulence of A. baumannii in iron-restricted environments such as the human body (Aghajani et al., 2019). The approaches under investigation include the use of gallium, a metal that mimics ferric iron but disrupts bacterial iron metabolism, and synthetic siderophore mimics that competitively inhibit receptor binding (Antunes et al., 2012). Siderophore receptors can be targeted as a vaccination strategy. Consequently, control strategies targeting such an iron metabolism may offer promising approaches to reduce the bacterial survival on surfaces.

Natural compound–based control strategies

Anti-biofilm and anti-virulent activities of natural extracts (halophyte plant extracts)

As antibiotic resistance continues to increase worldwide, there is increasing interest in plant-derived natural products as alternative strategies to control MDR pathogens, including A. baumannii. Plants, particularly those adapted to extreme environments, produce a diverse range of bioactive secondary metabolites as part of their adaptive mechanisms. Recent studies have investigated halophytes, salt-tolerant plants native to the coastal regions of Korea, as potential sources of anti-A. baumannii compounds. Crude extracts and solvent fractions of seven native Korean halophyte species were systematically screened for their ability to inhibit A. baumannii biofilm formation. Among the tested species, extracts from Peucedanum japonicum Thunb., a coastal herb commonly known as Japanese hog fennel, and Lysimachia mauritiana Lam., a salt marsh plant, demonstrated notable anti-biofilm activity against A. baumannii (Lee et al., 2024). The most active fractions—the 85% methanol fraction from P. japonicum and the n-hexane fraction from L. mauritiana—significantly reduced the biofilm biomass of A. baumannii ATCC 17978 in vitro. Interestingly, these plant fractions also exhibited strong antioxidant and anti-inflammatory properties. The P. japonicum fraction prolonged the survival of Caenorhabditis elegans nematodes infected with A. baumannii, indicating a reduction in bacterial virulence in a live host model (Lee et al., 2024). Concurrent antioxidant and antibiofilm activities are particularly interesting, as they may point to a potential mechanism of action. It is likely that plant-derived antioxidants interfere with the oxidative stress signaling pathways of A. baumannii (Abirami et al., 2023). In addition to their antioxidant effects, several plant-derived polyphenols have been shown to interfere with bacterial quorum sensing and surface adhesin expression. Although the specific active constituents of halophyte extracts are still under investigation, possible candidates include phenolic acids, flavonoids, and terpenoids, which are classes of compounds that are widely recognized for their antimicrobial properties (Ta and Arnason, 2015). Moreover, owing to their natural origin, such compounds may exhibit low toxicity and reduce the risk of antimicrobial resistance. Overall, halophyte-derived compounds represent a promising avenue for controlling A. baumannii by targeting biofilm development and virulence and serving as complementary strategies in combination with conventional sanitation.

Plant-derived antimicrobials (PDAs; trans-cinnamaldehyde, carvacrol, and thymol) and their mechanisms

Plant essential oils and their active constituents have long been recognized for their broad-spectrum antimicrobial properties. Several PDAs have shown efficacy against A. baumannii, either by directly inhibiting bacterial growth, reducing bacterial viability, or virulences (Table 1). Notable examples include trans-cinnamaldehyde, carvacrol, and thymol, which are bioactive compounds commonly found in spices and aromatic herbs. Trans-cinnamaldehyde is the principal aldehyde in cinnamon oil, whereas carvacrol and thymol are phenolic monoterpenes present in oregano and thyme oils, respectively. These agents have been tested against A. baumannii and have demonstrated broad antimicrobial activity. Notably, synergistic interactions have been reported in carvacrol or trans-cinnamaldehyde, resulting in a significant reduction in bacterial viability (da Silva et al., 2024; Montagu et al., 2016). PDAs exert their effects primarily by targeting bacterial cell membranes and inducing cellular stress responses. The lipophilic nature enables them to integrate into the lipid bilayer of the bacterial membrane, leading to increased permeability and leakage of essential intracellular components, such as ions and ATP. A. baumannii cells exposed to these compounds display typical signs of membrane disruption and bioenergetic collapse. In addition to membrane damage, PDAs can induce broader physiological disturbances. Exposure to carvacrol and trans-cinnamaldehyde has been shown to cause ribosomal RNA degradation in A. baumannii, suggesting interference with fundamental processes such as protein synthesis (Montagu et al., 2016). Notably, carvacrol appeared to be primarily responsible for this effect, as rRNA damage was evident when the compounds were delivered in encapsulated form, suggesting a direct molecular interaction between carvacrol and ribosomal components (Montagu et al., 2016). Notably, exposure to a mixture of carvacrol and trans-cinnamaldehyde significantly induced the expression of heat shock protein genes, including groES, groEL, dnaK, and clpB, and the oxidative stress defense gene katE, which encodes catalase. This pattern of gene activation suggests a direct molecular interaction between carvacrol and ribosomal components. The induction of catalase suggests that PDA exposure triggers oxidative stress in A. baumannii, likely owing to disrupted electron transport or the release of intracellular iron, which can lead to the formation of ROS. Taken together, these results indicate that compounds such as cinnamaldehyde and carvacrol exert multifaceted antibacterial effects. They damage membrane integrity, cause internal oxidative stress, and damage vital macromolecular structures such as ribosomes.

Table 1.

Natural compounds–based control strategies against A. baumannii

Natural compounds	Mechanism of action	Effectiveness (reduction in A. baumannii biofilm or cells)	References
Trans-Cinnamaldehyde	Disrupts cell membranes; interferes with quorum sensing and extracellular polymeric substance (EPS) production, leading to inhibition of biofilm formation	Approximately 50–70% biofilm reduction at sub-inhibitory concentrations (e.g. 1/2 MIC) Also increases antibiotic susceptibility by increasing envelope permeability	Mohamed et al. (2018), Karumathil et al. (2018)
Carvacrol	Causes membrane damage and depolarization; inhibits twitching motility required for biofilm establishment	Up to 95% inhibition of biofilm formation at 0.15 mg/mL (sub-MIC) Significantly reduces surface-attached cells (≥ 1 log CFU reduction) without affecting planktonic viability	Tapia-Rodriguez et al. (2023)
Thymol	Disrupts bacterial membranes and proton motive force; alters biofilm matrix synthesis and quorum sensing	Significant biofilm reduction (approximately 60% decrease in surface-associated viable cells at sub-MIC) Inhibits motility and works synergistically with antibiotics in biofilm control	Tapia-Rodriguez et al. (2023)
EDTA (Ethylenediaminetetraacetic acid)	Chelates divalent cations (Mg2⁺, Ca2⁺) that stabilize the outer membrane and biofilm EPS, leading to destabilized biofilms and increased cell envelope permeability	Anti-biofilm: Prevented 61–100% of initial surface adhesion Biofilm disruption: Killed cells in mature biofilms upon treatment (evidenced by Live/Dead staining)	Ramalingam and Lee (2018)
Lactoferrin (human/bovine)	Binds and sequesters iron (essential for bacterial growth) – creates iron starvation; also can disrupt cell membranes and trigger bacterial motility, preventing stabilization of biofilm	Inhibits biofilm formation at 125 µg/mL	Avery et al. (2021)

Thymol, a structural isomer of carvacrol, exhibits a similar mode of action; it depolarizes bacterial membranes and inhibits efflux pump activity (Gan et al., 2025). In addition to their direct bactericidal effects, low concentrations of PDAs have been reported to suppress biofilm formation and quorum sensing in various pathogens. In A. baumannii, this effect may involve downregulation of genes associated with pili or surface adhesins, thereby limiting biofilm development and surface colonization. Furthermore, PDAs enhanced the susceptibility of A. baumannii to conventional antibiotics. For example, cinnamaldehyde and eugenol have been found to improve antibiotic efficacy, possibly by destabilizing the bacterial membrane or inhibiting efflux pump activity (Karumathil et al., 2018). The observed synergistic potential of PDAs suggests their potential as supportive agents in antimicrobial therapy. The use of PDA together with conventional antibiotics may help restore effectiveness against drug-resistant A. baumannii strains. From a food-safety perspective, PDAs such as thymol and carvacrol, both classified as Generally Recognized as Safe (GRAS) for food use, show strong potential as natural preservatives or surface sanitizers to reduce contamination (Tapia-Rodriguez et al., 2023). Taken together, plant-derived antimicrobials offer a versatile approach to control pathogens. Therefore, PDA may be effective against a wide range of antibiotic-resistant A. baumannii strains, enabling their potential use in both clinical and food-related settings. Table 1 given below summarizes the various natural compounds investigated for controlling A. baumannii, their modes of action against the pathogen, and their efficacy in reducing bacterial growth and biofilm formation. The aforementioned findings emphasize the potential of natural compounds as a basis for developing new therapeutic and preventive strategies against A. baumannii. As conventional antibiotic options become increasingly limited, natural product–based agents are gaining attention for their unique mechanisms of action and ability to overcome existing antibiotic resistance. One major advantage is the chemical diversity of natural compounds, which allows them to interact with a wide range of bacterial targets that are not typically affected by standard antibiotics. Additionally, bacteria often lack existing resistance mechanisms against these structurally diverse molecules. For instance, flavonoids have been shown to inhibit bacterial enzymes and suppress toxin production, whereas essential oil components such as phenolic terpenes exert antimicrobial effects by disrupting cell membranes and other key structural elements (Paneri et al., 2023; Skariyachan et al., 2019). The proven effectiveness of halophyte-derived extracts and essential oil components in in vitro models supports their potential for clinical applications. Several strategies are feasible, including the development of plant-based surface sanitizers for clinical or food-processing settings and the isolation and optimization of individual bioactive compounds, such as rosmarinic acid or baicalein, which exhibit anti-A. baumannii activity. In addition, structural variants of these compounds can be synthesized to improve their effectiveness and stability.

Natural product–based novel therapeutics

These natural compounds can be used to control the virulence of A. baumannii, which involves the use of agents that inhibit the pathogen’s harmful functions rather than destroy it, supporting immune system–driven removal while reducing the risk of resistance development. Quorum-sensing inhibitors (QSIs) are a notable group of such compounds. A. baumannii relies on QS systems to regulate biofilm formation and possibly the expression of virulence factors. Plant-based QSIs, such as ajoene, a compound found in garlic, have been shown to disrupt QS signals, thereby reducing key pathogenic behaviors without applying bactericidal pressure. In addition to small-molecule inhibitors, quorum quenching (QQ) enzymes, which degrade QS signal molecules, represent another promising antivirulence strategy. These enzymes, such as MomL, which originate from certain bacteria or plants, can disrupt cell–cell communication in A. baumannii, thereby impairing coordinated behaviors such as biofilm formation and virulence expression (Abraham, 2016; Saipriya et al., 2020; Zhong and He, 2021). Natural compounds frequently exhibit multiple bioactive properties, including anti-inflammatory and immunomodulatory effects. This multifunctionality may be particularly beneficial in the context of A. baumannii infections, which are often associated with excessive inflammatory responses such as sepsis and pneumonia. Agents that inhibit bacterial growth and mitigate host-mediated inflammation can improve clinical outcomes by limiting tissue damage while controlling infection. However, the application of these promising findings in clinical or real-world settings requires further research. Major challenges include defining optimal dosing strategies, assessing safety and potential toxicity in humans, ensuring formulation stability, and developing appropriate delivery methods, such as aerosol sprays for lung infections or topical applications for wound treatment. From a food-quality perspective, it is also important to ensure that the use of natural compounds does not negatively affect food quality or conflict with existing regulations. Notably, many plant-based extracts, such as thyme oil, cinnamon, and other spice-derived ingredients, have already been approved as flavoring agents or preservatives, which may help regulatory acceptance.

In summary, natural product–based approaches represent a compelling and versatile strategy for the management of A. baumannii. These methods are aligned with the One Health approach, which addresses pathogens across clinical, environmental, and food-production settings. Utilizing the rich diversity of antimicrobial compounds found in nature, we may be able to develop new therapeutics and disinfectants that bypass traditional resistance mechanisms and support more sustainable pathogen control (Saipriya et al., 2020). The current screening of plant libraries, marine organisms, and microbial metabolites is expected to lead to the identification of new candidates with anti-A. baumannii activity. Combining these newly discovered natural products with data-driven methods such as predictive modeling to optimize timing, application conditions, and delivery routes can significantly improve the precision and effectiveness of pathogen control strategies. The integration of compound discovery and data science may accelerate the development of next-generation interventions for clinical and environmental settings.

Control measures in food-processing and -production environments

Hazard analysis and critical control point (HACCP) and good agricultural practices (GAP) implementation to mitigate contamination

Preventing A. baumannii contamination at all stages of food production is the most effective way to reduce its risks. This begins at the farm level with GAP and continues through processing via HACCP systems. While HACCP plans traditionally focus on well-known foodborne pathogens like Salmonella or Listeria, the same principles can be applied to A. baumannii: identifying points in the process where contamination may occur or spread and implementing controls to stop it. In primary production, GAP need to be implemented. These practices help prevent the introduction of environmental A. baumannii into crops or animals (Oyenuga et al., 2024; Wu-Wu et al., 2023).In food-processing environments, such as packaging facilities, dairy plants, and meat-processing operations, a HACCP-based system should include stringent Sanitation Standard Operating Procedures (SSOPs). Regular environmental surveillance for A. baumannii in food-processing facilities is necessary, especially in operations that produce ready-to-eat products for vulnerable populations. This approach is similar to current monitoring programs for Listeria monocytogenes. Upon the detection of A. baumannii, targeted sanitation efforts, including deep cleaning of drains, conveyor belts, and food-contact surfaces, can be implemented to eliminate localized contamination sources. Ultimately, strict compliance with HACCP and GAP/GMP remains the foundation of effective control. Maintaining high hygiene standards throughout the farm-to-fork continuum supports the primary goal of preventing A. baumannii entry into the food chain and its rapid removal when present. Although these preventive strategies are common in nature, they have been proven to be effective against A. baumannii and other foodborne and opportunistic pathogens (Awuchi, 2023; Oyenuga et al., 2024).

Biofilm inhibition techniques: applying iron chelators, iron mimetics, and antioxidants

Standard cleaning agents may be insufficient to remove resilient A. baumannii biofilms from food-processing environments, necessitating the development of specialized strategies targeting the biofilm mode of growth. One such approach involves iron chelation given the essential roles of iron in A. baumannii biofilm development and persistence. Chelating agents such as ethylenediaminetetraacetic acid (EDTA) sequester metal ions, including iron, and have been shown to destabilize biofilm architecture by disrupting metal-dependent structural integrity. Laboratory studies have demonstrated that EDTA and other similar compounds can enhance the susceptibility of A. baumannii biofilms to antibiotics and sanitizers by weakening the biofilm matrix (Lee et al., 2008).

Chelation-based strategies can be explored as “Trojan horse” tactics; for example, gallium, an iron mimic, can be internalized by A. baumannii and interfere with iron-dependent processes, thereby impairing bacterial viability (Runci et al., 2017).

It should be noted that external chelators alone did not uniformly reduce biofilm biomass across all strains, indicating variability in strain-level response and the need for combination approaches. In food-processing settings, the application of food-grade iron-binding agents such as citrate or lactoferrin to surfaces may help suppress bacterial growth by creating localized iron-depleted conditions. Lactoferrin, a milk-derived glycoprotein with intrinsic antimicrobial properties, binds to iron and has been shown to inhibit biofilm formation in various bacterial species, and may potentially have similar effects in A. baumannii (Avery et al., 2021).

Combining iron limitation with additional environmental stresses may produce an additive inhibitory effect on A. baumannii biofilm formation. Another complementary strategy involves the use of antioxidants and other biofilm-disrupting agents. Oxidative stress can trigger biofilm formation in A. baumannii. Therefore, maintaining antioxidant environment may reduce the stimulus for biofilm initiation. N-acetylcysteine (NAC), a well-known antioxidant, exerts biofilm-disrupting effects in certain pathogens by breaking disulfide bonds within the biofilm matrix and scavenging ROS. NAC also inhibits A. baumannii biofilm formation and enhances antibiotic penetration (Dinicola et al., 2014; Feng et al., 2018). In addition, many natural extracts, such as halophyte-derived polyphenols, exhibit both antioxidant and antibiofilm activities, supporting their potential utility in integrated control strategies (Lee et al., 2024). Natural compounds with antioxidant and antimicrobial properties can be used in surface treatments or to produce wash solutions to mitigate A. baumannii contamination. Plant-derived extracts included in produce washes can reduce surface bacterial loads on leafy greens while simultaneously inhibiting biofilm development in wash tanks and filtration systems. Several food-grade antioxidants, such as rosemary extract, are already approved as preservatives and may provide additional antimicrobial benefits (Abu El-Wafa et al., 2020; Grigore-Gurgu et al., 2025).

A more targeted strategy involves the enzymatic disruption of the biofilm matrix. Enzyme-based cleaners containing glycosidases, proteases, DNases, or polysaccharide-degrading enzymes such as dispersin B can break down extracellular polymeric substances (EPS), which are essential for biofilms. These enzymatic agents may be especially effective in clean-in-place (CIP) systems used in beverage and dairy processing, where they are used to remove biofilm residues from internal surfaces (Zhao et al., 2023). In practice, an integrated cleaning protocol may be the most effective. For example, combining a chelating agent such as EDTA with a biocidal agent such as peracetic acid can first disrupt the biofilm matrix and then improve the killing of embedded cells. A final rinse with an antioxidant solution such as ascorbic acid or lactoferrin can lower the chances of stress-induced biofilm regrowth. Importantly, all these approaches need to be validated for each strain because A. baumannii biofilm responses can vary widely depending on the environmental conditions and composition of the surrounding medium. Therefore, pilot-scale trials in food industry settings are essential to optimize the concentrations, combinations, and application protocols of biofilm-disrupting agents. Biofilm control remains a critical focus because established A. baumannii biofilms can persist in environmental niches and serve as chronic sources of contamination within processing facilities. Combining iron chelators, which nutritionally deprive biofilms, with antioxidants or enzymes, which dismantle their extracellular matrix, can markedly enhance biofilm removal compared with conventional sanitation alone. Notably, many of these strategies have been adapted from advances in medical biofilm control and may be integrated into food sanitation protocols to proactively manage resilient pathogens such as A. baumannii (Shrestha et al., 2022).

Big data and artificial intelligence (AI)-driven predictive models for risk assessment and prevention

Preventing foodborne infection by A. baumannii and other opportunistic pathogens can be significantly improved using predictive analytics. With advances in big data processing and AI, it is now possible to identify risk factors for microbial contamination early and implement timely and preemptive interventions. Modern food production systems generate extensive data streams, including sensor-based monitoring of temperature and humidity, microbial counts, supply chain traceability, laboratory test results, and genomic surveillance data. When processed using machine learning algorithms, this information can reveal patterns that signal an increased risk of contamination. For example, predictive models might show that the presence of A. baumannii in a ready-to-eat salad facility is linked to factors such as the source of the produce, brief drops in sanitizer levels, or weather-related changes in water quality. When these conditions reappear, AI systems could automatically alert quality assurance teams to intensify testing or sanitation (Abass et al., 2024). Another promising application of AI is the prediction of antimicrobial resistance (AMR) profiles (Gao et al., 2024). Machine learning models trained on genomic data have already demonstrated the ability to accurately predict antibiotic-resistance traits, thus providing a powerful tool for surveillance and preemptive response planning (Mishra et al., 2024; Yun et al., 2024). At a broader level, integrating public health surveillance data from clinical settings and food safety inspections can enhance source tracking. For example, if an AI-driven platform detects a genetic match between an A. baumannii cluster linked to hospital infections and strains isolated from a specific food product or facility, it can trigger targeted investigations before a formal outbreak is identified. These genomic epidemiological tools provide a preventive framework for pathogen tracking and intervention across public health and food safety systems (Savin et al., 2024).

Predictive microbiology is another relevant domain with significant potential for improving the control of A. baumannii in food systems. This field focuses on modeling bacterial behavior such as growth, survival, or inactivation under varying environmental parameters, including temperature, pH, and relative humidity. For A. baumannii, predictive models can be developed to estimate its growth kinetics in different food matrices or its thermal inactivation dynamics during cooking and sanitation. These models can be integrated into AI-driven decision-support systems to guide process optimization. For example, if input data indicate that A. baumannii may survive at specific sanitizer concentrations or exposure times, the algorithm could recommend protocol adjustments to enhance microbial control efficacy (Kumar et al., 2024; Taiwo et al., 2024).

Big data technologies also enhance traceability during outbreak events. In case of a suspected outbreak, genomic epidemiology, particularly WGS of A. baumannii isolates from food, environmental, and clinical sources, can be paired with AI-assisted phylogenetic analysis to rapidly identify transmission links. For example, the detection of a rare A. baumannii genotype in hospitalized patients could prompt an AI-driven comparison with existing genomic databases. If identical or closely related strains are found in food processing environments, the system can confirm a genetic match, enabling rapid identification of the source and implementation of appropriate control measures. Such approaches are effective for monitoring, and responding to foodborne outbreaks (Vilne et al., 2019).

Preventive maintenance protocols in food-production facilities may also benefit from AI. Real-time image recognition algorithms, potentially coupled with fluorescence imaging techniques, can be employed to detect early-stage biofilm formation on equipment surfaces and trigger timely notifications to sanitation personnel. Additionally, predictive maintenance schedules can be generated based on equipment usage patterns and historical contamination data. For example, an AI system could learn that a particular cutting machine tends to accumulate biofilms after 48 h of continuous operation, and recommend preemptive cleaning before the microbial risk escalates. Although such technologies are still under development, they are consistent with the principles of Industry 4.0, where smart manufacturing environments integrate Internet of Things (IoT) sensors and AI analytics to enhance process control, product safety, and quality assurance (Rojek et al., 2024; Rugji et al., 2024).

In summary, AI-driven predictive modeling offers a transformative approach to food safety by enabling early identification of risk factors. Machine learning algorithms, which have already been successfully applied to predict antimicrobial resistance in foodborne pathogens, can shift industrial and public health responses from reactive containment to proactive prevention. This is particularly relevant for A. baumannii, whose sporadic occurrence in food systems may go unnoticed until it becomes an entrenched source of contamination. Early prediction and targeted intervention may be the key to preventing its establishment in food-production environments. As genomic surveillance expands and data sharing improves, supported by the collection of whole-genome sequences and environmental metadata, AI-based tools will grow in accuracy and utility, forming an integral component of comprehensive strategies to mitigate A. baumannii as an emerging food safety threat (Feretzakis et al., 2021; Hu et al., 2023; Jia et al., 2024).

Taken together, A. baumannii represents a growing concern as both a nosocomial and emerging foodborne pathogen. Its ability to persist in food-processing environments, resist conventional disinfectants, and spread silently through asymptomatic colonization highlights the urgent need for improved control measures. Innovative strategies such as the application of natural antimicrobials like cinnamaldehyde and carvacrol, along with iron-chelating agents that disrupt biofilms, should be actively explored and incorporated into hygiene protocols. At the same time, food safety surveillance must be strengthened through AI-assisted genomic characterization and real-time data sharing to enhance early detection and risk assessment. Future research should aim to validate these control methods under real food industry conditions and investigate the survival and stress response mechanisms of A. baumannii in diverse food matrices. A proactive, integrated One Health approach supported by collaboration among researchers, regulators, and industry professionals is essential to effectively reduce the foodborne risk of A. baumannii and safeguard the global food system.

Funding

This research was supported by the Main Research Program (E0210701-05) of the Korea Food Research Institute (KFRI), funded by the Ministry of Science and ICT.

Declarations

Conflict of interests

The authors declare no conflicts of interest.