The fatty acid synthesis gene fabY affects lipopolysaccharide synthesis and colistin susceptibility in Pseudomonas aeruginosa

ABSTRACT Bacterial metabolism impacts susceptibility to antibiotics. Here, we found that mutation of the Pseudomonas aeruginosa fatty acid response regulator gene pvrA decreases bacterial susceptibility to colistin. The fatty acid synthesis gene fabY is upregulated in the pvrA mutant. Deletion of fabY in either the pvrA mutant or wild-type strain increases bacterial susceptibility to colistin. Further investigation reveals that the mutation of fabY enhances lipopolysaccharide production, thereby increasing the surface binding of colistin and bacterial susceptibility. IMPORTANCE This project explored the influence of bacterial metabolism on antibiotic sensitivity and found a new mechanism to make Pseudomonas aeruginosa sensitive to colistin by interfering with fatty acid synthesis. In this study, it was observed that the mutation of the fatty acid metabolism regulation gene pvrA in P. aeruginosa reduced the susceptibility of bacteria to colistin. It was also found that the fatty acid synthesis gene fabY was up-regulated in the pvrA mutant. Further investigation showed that the fabY mutation enhanced the production of lipopolysaccharide and increased the surface binding and bacterial sensitivity of colistin. This study shows that the therapeutic effect can be enhanced by developing fatty acid synthesis inhibitors combined with polymyxin, and it provides a new target for antibiotic treatment.