TRANSCRIPTOMIC STUDY REVEALS NEW PATHWAYS and GENES INVOLVED in Enterococcus faecalis V583 RESPONSE to a THERAPEUTIC DOSE of VANCOMYCIN

Title:Transcriptomic study reveals new pathways and genes involved in Enterococcusfaecalis V583 response to a therapeutic dose of vancomycin.Background: An enterococcalstrain carrying the VanB resistance type can become susceptible if impaired inother genes unrelated to the vanB operon. This fact alone illustratesthe lack of knowledge on the vancomycin mode of action. This antibiotic is stillusable to treat serious infections caused by multiresistant enterococcalstrains, but may not be so for long. This work was thus set up to gather a bodyof knowledge that can be used in the future to increase efficacy against bothvancomycin resistant (VRE) and susceptible enterococci (VSE). Methods and Findings: Microarrays were used to detect the genetic response of theVanB carrying strain Enterococcus faecalis V583 to a therapeutic dose(10 mg/ml) ofvancomycin. Besides the vanRS genes, two other two-component systemswere induced. The therapeutic dose of vancomycin was found to act as ananti-virulence agent, by turning-off the Fsr quorum-sensing system. Key regulators and metabolic enzymes,involved in trafficking carbon sources into glycolysis and isoprenoid synthesisand utilization, were also affected in order to support cell-wall synthesis.Also, cell-wall modification involving lipotheicoic acid synthesis, DNA repairand protein folding were highly responsive functions to the vancomycin dosetested.Conclusions:Overall, our results provideclues on the ability of a VRE strain to stand vancomycin and on the mode ofaction of the antibiotic. VRE response to a vancomycin therapeutic doseinvolves an intricate regulatory network and metabolic adjustment which isworth solving as it can help finding new targets to fight both VRE and VSEinfections.



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