Table 1.
Strategies aimed at preventing biofilm formation by A. baumannii.
| Strategy | Strains/Isolates | Antibiofilm Activity | Antibiofilm Mechanisms | Reference |
|---|---|---|---|---|
| Pyrogallol (polyphenolic organic compound from galls and barks of various trees) | MTCC 9829 reference strain | MBIC: 20 μg/mL | Reduced CSH Reduced motility (swarming) Reduced EPS production Downregulation of adhesion-related genes (ompA, csuA/B) Downregulation of bap gene involved in biofilm formation and stabilization |
[138] |
| Myrtenol (bicyclic monoterpene derived from various plants) | ATCC 19606 and MTCC 9826 reference strains Clinical isolates (n = 2) |
MBIC: 200 μg/mL CLSM showed reduced biomass, maximum thickness, and surface-to-volume ratio |
Reduced CSH Reduced motility (swarming, twitching) Downregulation of biofilm-associated genes (bfmR, csuA/B, bap, ompA, pgaA, pgaC) |
[139] |
| Curcumin (flavonoid) | A. baumannii ATCC 17,978 reference strainClinical isolates (n = 8) | Biofilm inhibition by: 46% at 20 μg/mL 93% at 100 μ/mL |
Reduced motility (swimming, swarming) Interaction with the biofilm response regulator BfmR |
[140,141] |
| 5-hydroxymethylfurfural (furan organic compound derived from the dehydration of reducing sugars) | ATCC 19606 reference strain | MBIC: 100 μg/mL | Reduced CSH Reduced motility (swarming, twitching) Reduced EPS production Downregulation of biofilm-related genes (bap, csuA/B, ompA, bfmR, katE) |
[142] |
| Synthetic peptide Cec4 | Carbapenem-resistant isolates (n = 200) | MBIC: 64–128 µg/mL | Reduced motility (twitching) Downregulation of biofilm-related genes (csuE, bfmR and bfmS, bap) |
[143] |
| CFS from Clostridium butyricum | ATCC 19606 reference strain MDR clinical isolates (n = 2) |
Biofilm inhibition by: 24.4–33.9%, at 12.5% CFS 28.2–43.1%, at 25% CFS 93.6–99.6%, at 50% CFS |
Reduced motility Downregulation of RND-type efflux pump-related adeABC genes |
[144] |
| Non-native AbaR antagonists | M2 abaI::lacZ (ΔabaI reporter) and M2 wild-type | Biofilm inhibition by 40% | QS inhibition | [145] |
| Siphonocholin (from marine sponge Siphonochalina siphonella) | ATCC BAA747 reference strain | Biofilm inhibition by 70% | QS inhibition Reduced motility (swarming) Reduced EPS production |
[146] |
| Flavonoid-rich active fraction F1 (from Glycyrrhiza glabra) | ATCC 19,606 and ATCC 17,978 reference strains Clinical isolates (n = 5) |
Concentration-dependent effect Maximum biofilm inhibition by 30–70%, at 2 mg/mL |
QS inhibition by abaI downregulation Reduced motility (twitching) |
[147] |
| Linalool (oil compounds from Coriandrum sativum) | LMG 1025 and LMG 1041 reference strains Clinical isolates (n = 3) |
Concentration-dependent effect: 1–18%, at 0.25 × MIC 75–97.1%, at 4 × MIC |
Reduced adhesion QS inhibition |
[148] |
| Pentacyclic triterpenoids (betulinic acid, glycyrrhetinic acid, ursolic acid) | ATCC 19606 reference strain | Biofilm inhibition (respectively at 50, 100 and 200 µg/mL): 36, 56, 80% (glycyrrhetinic acid) 31, 63, 88% (ursolic acid) 45, 62, 88% (betulinic acid) |
QS inhibition (at AHL synthase and AHL dependent transcriptional activator) Reduced EPS production |
[149] |
| MomL (AHL lactonase belonging to the metallo-β-lactamase superfamily) | LMG10520, LMG10531 and AB5075 reference strains | Concentration-dependent effect Maximum biofilm inhibition by 42% at 5 µg/mL |
AHL degrading activity | [119] |
| Purified QQ enzyme Aii20J | ATCC17978 reference strain MDR clinical strains (n = 5) |
Biofilm inhibition by 80% The effect is strain-dependent and improved when QQ enzyme is combined with DNase |
Decreased the number of surface short pili | [150] |
| Palmitoleic acid, myristoleic acid (unsaturated fatty acids) | ATCC17978 reference strain Clinical isolates (n = 22) |
Biofilm inhibition (at 0.02 and 0.05 mg/mL, respectively) by: 37 and 39% (palmitoleic acid) 28 and 42% (mirystoleic acid) Significant biofilm reduction in: 13 isolates (palmitoleic acid) 8 isolates (mirystoleic acid) |
Inhibition of abaR gene expressionAccumulation of fatty acids at the air−liquid interface, due to their amphiphilic nature | [151] |
| Al2O3 synthetic NPs | MDR strains (n = 3) | Biofilm inhibition by 11.6 to 70.2% at 0.5xMIC | Reduced EPS production | [152] |
| Labetalol hydrochloride (Wzb-Wzc interaction inhibitor) | RS 307 reference strain | MBIC: 1 mM | Reduced EPS production | [153] |
| Chitosan-coated human albumin nanoparticles for the delivery of colistin (Col/haNPs) | ATCC 19,606 reference strain Colistin-susceptible (n = 1) and -resistant (n = 3) clinical isolates |
Significant biofilm inhibition at 1/2x and 1/4xMIC Col/haNPs > 4–60-fold vs. free colistin |
Positively charged NPs might adsorb and accumulate on the negatively charged bacterial surface and EPS by electrostatic interactions Prolonged release of colistin Chitosan−colistin synergistic effect |
[154] |
| Polyclonal antibodies vs. self-complemented CsuA/B subunit (αA/B) and CsuENTD (αEN) | Clinical strains (n = 5) | αEN inhibits biofilm formation more efficiently than αA/B: αEN diluted up to several thousand times completely blocked biofilm formation αA/B inhibited biofilm formation only at high concentration |
Inhibition of the binding to hydrophobic plastics by blocking the three hydrophobic fingers at the tip of CsuE N-terminal domain (CsuENTD) | [43] |
| Cationic amphiphilic peptide zp3 (GIIAGIIIKIKK-NH2) | ATCC 19606 reference strain | Biofilm inhibition by: 20%, at 0.5 μM 100%, at >4 μM |
Destabilization of cell membranes with pore formation and consequent biofilm collapse | [155] |
| Pro10-1D (a short peptide from insect defensin) | KCCM 40203, CCARM 12010 and CCARM 12220 reference strains | Concentration-dependent effect: 20% inhibition at 2 µM >99.9% inhibition at 64 µM |
Reduced EPS production | [156] |
| 24 indole derivatives (including 16 halogenated indoles) | ATCC 17978 and ATCC BAA-1709 reference strains MDR clinical isolates (n = 7) |
Biofilm inhibition at 50 µg/mL: 62% (4-bromoindole) 75% (4-chloroindole) 60% (4-iodoindole) 94% (6-iodoindole) 96% (5-iodoindole) |
Reduced surface motility Induced reactive oxygen species, resulting in loss of cell membrane integrity and cell shrinkage |
[157] |
| PDI mediated by indocyanine green encapsulated in chitosan nanoparticles (NCs@ICG-aPDT) | Isolates from burn wounds (n = 50) | Biofilm inhibition by: 55.3% after exposure to NCs@ICG-aPDT No inhibition after exposure to NCs@ICG, ICG, and the diode laser alone |
Bactericidal effect | [158] |
| PDI of nanoliposomal silver sulfadiazine doped with curcumin (AgSD-NLs@Cur) | Isolates from burn wounds (n = 100) | Biofilm inhibition by 76.4% after exposure to AgSD-NLs@Cur at MIC90 and light-emitting diode Photoexcited AgSD and AgSD-NLs at MIC90 are more effective than either group without LED irradiation (38.1 vs. 44.8%, respectively) |
Ag in AgSD-NLs interacts with DNA and sulfhydryl groups of microbial enzymes, leading to bacterial growth inhibition Downregulation of luxI gene |
[159] |
| Endolysin Abtn-4 from phage vB_AbaP_D2 (isolated from hospital wastewater) | Clinical MDR isolates (n = 15) AB9 host strain |
Biofilm inhibition > 30% following exposure in the early (12 h post-incubation) or pre-maturation phase (36 h post-incubation) | EPS disruption Bacterial cell wall degradation |
[160] |
| Pentacyclic triterpenoids, (glycyrrhetinic acid, ursolic acid, betulinic acid) combined with a conventional antibiotic (doxycycline, roxithromycin or ciprofloxacin) | ATCC 19606 reference strain | Glycyrrhetinic acid and betulinic acid increase antibiofilm activity of doxycycline and roxithromycin Ursolic acid improves the effect of ciprofloxacin |
Increased antibiotic diffusion through biofilm mediated by the triterpenoids | [149] |
| Biofilm inhibitors (zinc lactate, stannous fluoride, furanone, AZM, and RIF) combined with a conventional antibiotic (IMP, MRP, TIG, POL) | XDR clinical isolates (n = 9) | Biofilm inhibition: 16 to 50%, at sub-MICs lactate > stannous fluoride > furanone > RIF > AZM Synergistic effects of: zinc lactate, stannous fluoride and furanone combined with TIG (22, 56 and 11% of the isolates, respectively) zinc lactate and stannous fluoride each used with a carbapenem (IMP or MRP), in 33% of the isolates |
Zinc compounds inhibit EPS synthesis and the formation of matrix networks Stannous fluoride destroys the biofilm structure by loosening the structure of the biofilm matrix Furanone replaces the binding sites of QS signal molecules Azithromycin inhibits EPS production, leading to the formation of channels that favor antibiotic diffusion through the biofilm |
[161] |
| Phenanthroline-based visible-light-activated manganese (I) carbon-monoxide-releasing molecules (PhotoCORMs) | ATCC BAA 1710 and ATCC 17978 reference strains | Biofilm formation inhibition only at high concentrations (>128 mg/mL) in the dark Compounds 1-2 reveal remarkable activity at 4–8 mg/mL when irradiated with blue LED light Compound 2 shows higher activity than ciprofloxacin vs. MDR ATCC BAA 1710 strain |
Antibacterial activity due to the combination of CO release as well as the production of photo-byproducts | [162] |
| Maipomycin A (from the metabolites of the marine actinomycete Kibdelosporangium phytohabitans XY-R10) | ATCC 19606 reference strain | Biofilm inhibition by 84.3% at MBIC (8 μg/mL) Concentration-dependent effect Inhibition of biofilm formed on medical materials, such as catheters (silicone) and endotracheal tubes (polyvinyl chloride) |
Fe(II) and Fe(III) ions chelation The chelation of Maipomycin A and iron ions may be negatively affected by other metal as competitors |
[163] |
| ZY4 cyclic synthetic peptide (designed on cathelicidin-BF15 and stabilized by a disulfide bridge) | ATCC 22933 reference strain MDR clinical isolates (n = 5) |
Concentration-dependent effect 22%, at 0.5xMIC 46%, at 2xMIC 66%, at 8xMIC |
Bactericidal effect by permeabilizing the cell membrane | [164] |
| Chitosan hydrogels loaded with AgNPs and AMP | Carbapenem-resistant isolate from CVC | Biofilm viability inhibition on CVC: 1 log10 (chitosan) 10 log10 (chitosan with 25 ppm AgNPs and 50 ppm AMP) |
NS | [165] |
MBIC, minimum concentration of drug that exhibits greater than 50% of biofilm inhibition without affecting growth; CSH, cell surface hydrophobicity; EPS, extracellular polymeric substance; CLSM, confocal laser scanning microscopy; CFS, cell-free supernatant; MDR, multidrug resistant; QS, quorum sensing; MIC, minimum inhibitory concentration; AHL, N-acyl-homoserine lactone; QQ, quorum quenching; NPs, nanoparticles; PDI, photodynamic inactivation; AZM, azithromycin; RIF, rifampicin; XDR, extensively drug resistant; IMP, imipenem; MRP, meropenem; TIG, tigecycline; POL, polymyxin B; AMP, ampicillin; CVC, central venous catheter; NS, not specified.