D-110. Transcriptomic Profile of E. faecalis to a Therapeutic Dose of Vancomycin
Enterococci are harmless in healthy individuals but constitute a serious threat to patients with compromised immune system or under prolonged antibiotic treatments. Isolation of enterococci responsible for nosocomial infections has grown in parallel with the use of antibiotics. In fact, this genus has an extraordinary ability to survive to a wide range of environmental stresses, in which category exposure to antibiotics may be included. The use of vancomycin, a glycopeptide antibiotic, to treat multiresistant enterococcal infections is now close to became obsolete due to increasing isolation of VRE. The vancomycin stress response was studied in E. faecalis V583. A therapeutic dose of vancomycin drastically affected the transcriptional profile of the bacteria. About 12.3% of the predicted V583 genes were found to be differentially transcribed. The study was done at two different exposure times (t10min and t30min) to resolve antibiotic stress effects occurring on two biologically relevant time scales. The expression of 205 genes after 10 minutes of exposure to the antibiotic, and of 445 genes after 30 minutes of exposure was affected. The genes differentially expressed mainly encode regulatory and signal transduction functions, transport and binding proteins and cell envelope proteins. The differential expression of genes involved in transport and binding and in cell envelope metabolism suggest that transport and maintenance of cell integrity are key factors in stress response to vancomycin. The two component systems (TCS) vanRS, croRS and ehk06-err06 responded to antibiotic treatment as well as the pleiotrophic regulator codY. The upregulated TCS are important for the specific response of V583 to vancomycin. In conclusion, microarray data demonstrated that E. faecalis respond globally to therapeutic vancomycin doses, suggesting that survival/resistance to this antibiotic may involve other cell elements than just the van resistance genes. This knowledge might help future research for other ways of fight enterococcal infections.