Transcriptomic study reveals new pathways and genes involved in Enterococcus faecalis V583 response to a therapeutic dose of vancomycin

Tânia Ribeiro, Neuza Teixeira, Ryoji Yokohata, Jiro Nakayama, Michael S. Gilmore, Maria de Fátima S. Lopes

Research output: Contribution to journalArticlepeer-review


Background: An enterococcal strain carrying the VanB resistance type can become susceptible if impaired in other genes unrelated to the vanB operon. This fact alone illustrates the lack of knowledge on the vancomycin mode of action. This antibiotic is still usable to treat serious infections caused by multiresistant enterococcal strains, but may not be so for long. This work was thus set up to gather a body of knowledge that can be used in the future to increase efficacy against both vancomycin resistant (VRE) and susceptible enterococci (VSE). Methods and Findings: Microarrays were used to detect the genetic response of the VanB carrying strain Enterococcus faecalis V583 to a therapeutic dose (10 mg/ml) of vancomycin. Besides the vanRS genes, two other two-component systems were induced. The therapeutic dose of vancomycin was found to act as an anti-virulence agent, by turning-off the Fsr quorum-sensing system. Key regulators and metabolic enzymes, involved in trafficking carbon sources into glycolysis and isoprenoid synthesis and utilization, were also affected in order to support cell-wall synthesis. Also, cell-wall modification involving lipotheicoic acid synthesis, DNA repair and protein folding were highly responsive functions to the vancomycin dose tested. Conclusions: Overall, our results provide clues on the ability of a VRE strain to stand vancomycin and on the mode of action of the antibiotic. VRE response to a vancomycin therapeutic dose involves an intricate regulatory network and metabolic adjustment which is worth solving as it can help finding new targets to fight both VRE and VSE infections.

Original languageEnglish
JournalArchives of Clinical Microbiology
Issue number1
Publication statusPublished - 2014

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)
  • Infectious Diseases


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