Phosphate transport system mediates the resistance of Enterococcus faecalis to multidrug
Lifan Wei1, Mingwei Li2, Feng Xia3
1Department of Endodontics and Operative Dentistry, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China; National Clinical Research Center for Oral Diseases, Shanghai, China; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China.
Abstract:
Enterococcus faecalis, a severe nosocomial and community opportunistic pathogen, is difficult to control due to its multidrug resistance. Through heredity and the recombination of intrinsic resistance genes and horizontally acquired resistance genes, E. faecalis can rapidly evolve drug resistance. Nisin, an important antimicrobial peptide, is extensively employed in the healthcare and food industries to inhibit Gram-positive bacteria and may induce the emergence of nisin-resistant bacteria worldwide. However, the mechanism governing nisin resistance in E. faecalis has not been fully elucidated. This study utilizes transposon insertion sequencing (TIS) to comprehensively explore novel genes related to nisin resistance. According to the analysis of TIS results, hundreds of genes appear to be essential for nisin resistance in E. faecalis. The phosphate transport system (OG1RF_10018-10021, named PTS), which is screened by TIS results, enhances the resistance of E. faecalis to nisin, the mechanism of which may be involved in potA and/or OG1RF_10526 (hypothetical gene). Meanwhile, PTS also strongly represses the biosynthesis of ribosomes to increase the sensitivity of E. faecalis to gentamycin. In addition, the overexpression of PTS increases the sensitivity of E. faecalis to daptomycin, the mechanism of which is independent of the LiaFSR system. This study first demonstrated that E. faecalis utilizes PTS to mediate the resistance to multidrug, which may help to elucidate the mechanism governing drug resistance and to establish guidelines for the treatment of infectious diseases caused by E. faecalis.
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