Editorial: Antimicrobial Resistance Along the Food Chain: Are We What We Eat?

Antimicrobial resistance (AR) is considered a “silent pandemic” that is responsible for more than 700,000 deaths per year; a figure that could rise to 10 million by 2050 if no action is taken (de Kraker et al., 2016; Mahoney et al., 2021). The use or rather misuse of antimicrobial drugs in hospitals has long been recognized as the main cause for the spread of antimicrobial resistant genes (ARGs) and this has become even more apparent during the SARS-CoV-2 pandemic where antimicrobial drugs were often prescribed unnecessarily to threat secondary infections (Knight et al., 2021; Russell et al., 2021; Wang et al., 2022).

In recent years, food production and agriculture among other anthropogenic activities, have exacerbated this problem (Van Boeckel et al., 2015; Wong et al., 2015; Caniça et al., 2019; Rozman et al., 2020; Schar et al., 2021). While the impact of clinical antimicrobial use and resistance has been well-documented, the contributions from other sources and how they fit into the overall prevalence of AR is less understood (Larsson and Flach, 2021). The underlying problem of AR is further complicated by the dynamic transmission of AR leading to the establishment of ARG reservoirs across various stages along the food chain (Imperial and Ibana, 2016; Hudson et al., 2017).

This Research Topic aims to offer a balanced overview of this global threat by gathering research focusing on AR along the food chain, from farm to fork. A total of 13 original research articles across China, India, Brazil, Malaysia, Spain, Iran, Egypt, and South Africa, have been published. Studies predicted that an overwhelming majority of people falling into poverty due to AR, will come from developing and underdeveloped countries, and our article collection reflects this geographical representation (Jit et al., 2020; Iskandar et al., 2021).

To demonstrate that farm animals are critical source for the dissemination of AR, Wu et al. evaluated the prevalence of Salmonella in a pig slaughtering house in China and found that the dehairing (66.66%) and splitting (57.14%) areas were the most contaminated with Salmonella. High frequency of resistance to tetracycline, ampicillin, chloramphenicol, and nalidixic acid, was also detected in the isolates. Bioinformatics analysis predicted a high dominance of S. Typhimurium ST19 among the isolates while several toxin encoding virulence factors were also identified.

In another study conducted on ducks in China, Wang et al. detected many ARGs from New Delhi metallo β-lactamase (NDM)-producing Escherichia coli isolates. Phenotypically, they show high frequency of resistance to trimethoprim-sulfamethoxazole, gentamicin, and fosfomycin. Conjugation experiments showed that the bla_NDM-carrying plasmids is transferrable. Moreover, bla_NDM coexisted with other ARGs which suggests plausible transfer of ARGs among intestinal E. coli isolates of ducks.

A similar study conducted on shrimp aquaculture farms in India by Sivaraman et al. found that extended-spectrum β-lactamase (ESBL)-producing E. coli and Klebsiella pneumoniae isolates were resistant to cefotaxime, tetracycline, ciprofloxacin, and trimethoprim-sulfamethoxazole. At the molecular level, high prevalence of ARGs responsible for conferring resistance to β-lactamase (e.g., bla_CTX−M), tetracyclines, sulfonamide and quinolone resistance, was detected.

In another study from Brazil, Cardozo et al. also detected high prevalence of bla_CTX−M in ESBL-producing E. coli and K. pneumoniae isolated from chicken, chicken meat, and human feces. The authors found high frequency of bla_CTX−M−15 among the isolates although they are genetically diverse, which suggests that farm animals and their by-products, could be a source of transmission for ESBL-producing pathogens to humans.

In Malaysia, Zakaria et al. reported that S. enteritidis isolated from humans, poultry, and foods, was resistant to multiple drugs. ARGs responsible for resistance to aminoglycosides and tetracyclines were the most abundant, while other ARGs responsible for resistance to ampicillin, sulfonamide, and ciprofloxacin, were also detected. Similar to the findings of Cardozo et al., S. enteritidis isolates from the various sources share similar resistant genetic traits although they are from distinct lineages.

Zhang et al. also detected resistance to aminoglycosides in Campylobacter isolates from chicken and swine in China. The corresponding ARGs were determined, and conjugative experiments confirmed the transferability of aminoglycoside resistance among C. jejuni strains. The gene fragment responsible for the elevated resistance in recipient strains was also characterized.

Another study on aminoglycoside resistance by Lu et al. found that the prevalence rates of 16S rRNA methylation enzyme (armA)-harboring Salmonella strains were 1.1/1,000 and 8.7/1,000 in outpatient and food or environmental isolates, respectively. All armA-harboring Salmonella strains were resistant to multiple drugs. The armA gene was determined to be plasmid-borne and could be transferred to E. coli and Acinetobacter baumannii. Importantly, strains isolated from outpatients were genetically more identical to those from poultry than those from swine, thus inferring that poultry consumption is a credible source of infection.

In Egypt, Saber et al. examined methicillin- and vancomycin-resistant Staphylococcus aureus (MRSA and VRSA) isolated from ready-to-eat meat and food handlers. MRSA isolates were resistant to cefepime, penicillin, ampicillin-sulbactam, ciprofloxacin, nitrofurontoin, and gentamicin, while VanA and VanB resistant genes were detected in VRSA. Importantly, the isolates could form biofilm and they harbor several biofilm-forming genes, which suggest greater risk of colonization and dissemination.

In South Africa, Richter et al. detected multi-drug resistance in ESBL/AmpC β-lactamase(AmpC)-producing E. coli, K. pneumoniae, Serratia fonticola, and S. enterica isolates from spinach and irrigation water. Genes coffering resistance to different classes of antibiotics were detected with bla_CTX−M−15 and bla_ACT-types being the most dominant. In silico analysis predicted high similarities to human pathogens for all strains, implying contamination mediated by anthropogenic activities.

A large-scale resistome analysis of Campylobacter spp. genomes by Cobo-Díaz et al. found resistant determinants of β-lactams, tetracyclines, quinolones and aminoglycosides in their genomes many of which, are also frequently found together with genes conferring resistance to other antibiotics. The genomes of isolates from humans, food animals, and foods, contain higher frequency of ARGs responsible for resistance to tetracyclines and quinolones, possibly due to intense use of these drugs in veterinary and clinical settings.

Li et al. sequenced three multi-drug resistant Listeria innocua isolates from food. Unlike the listeriosis causing L. monocytogenes, L. innocua is not infectious but, the authors identified ARG islands in both chromosomes and plasmids. All isolates contain the pathogenicity island-4 (LIPI-4) and phylogenetic analysis revealed that they share common origins, thus suggesting transmission capability. This study advocates for surveillance on non-infectious strains to reveal the origins and concomitantly, track and contain the spread of AR in foods.

In hospitals, tigecycline and colistin are last-resort antibiotics used to threat infections. In this regard, Moghimi et al. investigated the mechanisms of tigecycline resistance and found that many non-susceptible Klebsiella pneumoniae isolates from human, food animals and/or laboratory selection experiments, are resistant to a combined treatment of tigecycline and colistin. All isolates from humans carried carbapenemase genes while high frequency of mutations in genes that led to increased expression of the AcrAB efflux pump, was detected. Since tigecycline is not used in animal farming, the detection of tigecycline resistance in animal isolates is thus, a clinical concern.

Environmentally sustainable approaches are being increasingly sought to eliminate ARGs from animal farming and in this regard, Peng et al. reported that treatment of animal manure with high heat effectively reduced ARGs introduced into soils. The authors showed that ARG abundance in chicken manure-treated soils was 1.41 times higher than that in mushroom residue-treated soils, but this difference was abrogated when heat-treated chicken manure-amended soils was used.

Contributions in this Research Topic incorporated a variety of approaches to collectively advance our understanding of AR across the different components beginning from farms and ending with the consumers. Through horizontal gene exchanges along the food chain, ARGs inevitably end up interacting with human microbiomes [EFSA Panel on Biological Hazards (BIOHAZ) et al., 2021]. Therefore, we hope this collection will encourage further research, and establish or expand AR surveillance in agriculture, environment, and food processing systems.

Author Contributions

AW drafted the manuscript. All authors read, edited, and approved it for publication.

Funding

AW would like to acknowledge funding from Wenzhou-Kean University under the Student Partnering with Faculty (SpF) research program (SpF2021002).

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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