Abstract
Acinetobacter baumannii is a nosocomial pathogen, and its biofilms are tolerant to desiccation, nutrient starvation, and antimicrobial treatment on biotic and abiotic surfaces, tissues, and medical devices. Biofilm formation by A. baumannii is triggered by a quorum sensing cascade, and we hypothesized that fatty acids might inhibit its biofilm formation by interfering with quorum sensing. Initially, we investigated the antibiofilm activities of 24 fatty acids against A. baumannii ATCC 17978 and two clinical isolates. Among these fatty acids, two unsaturated fatty acids, nervonic and oleic acid, at 20 μg/mL significantly inhibited A. baumannii biofilm formation without affecting its planktonic cell growth (MICs were >500 μg/mL) and markedly decreased the motility of A. baumannii but had no toxic effect on the nematode Caenorhabditis elegans. Interestingly, molecular dynamic simulations showed that both fatty acids bind to the quorum sensing acyl homoserine lactone synthase (AbaI), and decent conformational stabilities of interactions between the fatty acids and AbaI were exhibited. Our results demonstrate that nervonic and oleic acid inhibit biofilm formation by A. baumannii strains and may be used as lead molecules for the control of persistent A. baumannii infections.
Highlights
Slightly different responses were observed between strains, American Type Culture Collection (ATCC) 17978 and BAA 1709 appeared to be more susceptible to the cis configuration middle and long-chain fatty acids (≤10 carbon atoms)
It was reported that myristoleic and palmitoleic acid decreased A. baumannii ATCC 17978 biofilm formation [32], which was consistent with the results observed in this study
None of the three fatty acids inhibited the planktonic growth of A. baumannii at 20 μg/mL, and their minimum inhibitory concentrations (MICs) were all above 500 μg/mL. These results showed that three fatty acids only prevented biofilm formation by A. baumannii strains at sub-inhibitory concentrations, indicating nervonic and oleic acid may be less prone to the development of drug resistance in A. baumannii
Summary
Biofilms are matrix-enclosed communities and enable bacteria to resist host defenses and antibiotics [1,2], and bacteria in biofilms can endure for extended periods and are difficult to eradicate in hospital settings [1]. Acinetobacter baumannii was ranked by the World Health Organization as a highest priority critical pathogen in 2017 and the most successful multidrug-resistant ESKAPE organism (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, A. baumannii, Pseudomonas aeruginosa, Enterobacter organisms) [3,4,5]. A. baumannii causes a wide range of infections, including pneumonia, bacteremia, endocarditis, osteomyelitis, meningitis, and severe nosocomial wound infections, urinary tract infections, bloodstream, skin, and other soft tissue infections [6,7,8]
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