Leona Zieglerováis
Charles University , Czech Republic
Title: The role ofvanZexpressionforefficiencyofglycopeptidesagainstStaphylococcus aureus
Biography
Biography: Leona Zieglerováis
Abstract
Glycopeptide antibiotics are used as last choice antibiotics for treatment of infections, caused by gram-positive bacteria. But, increasing occurrence of glycopeptide resistant strains in recent years, rapidly decreases the range of treatment options of the bacterial infections. The glycopeptide resistance may be connected to expression of van resistance gene cluster, which alters the binding site of the glycopeptides. VanZ, one gene, from this cluster, expressed in Enterococcus faecalis confers specific resistance to teicoplanin without expressed other genes from this cluster (Arthur et al, 1995). VanZorhologs, forming big VanZ like protein family, are present in many bacterial genomes and their function is unknown. In this study, we compared the ability of two orthologous genes,vanZfrom the vanRSHAXYZ cluster (vanZTei) and vanZ from the genome of Enterococcus faecium (vanZg,), to confer resistance to glycopeptides, when expressed in Staphylococcus aureus RN4220. We have shown that VanZg, but not VanZTei, decreases 4 times sensitivity of S.aureustoteicoplanin. Rate of resistance depends on the level of induction of gene expression.Both genes were not able to confer resistance to vancomycin or other non-glycopeptide antibiotics; however, they effect decrease bacteria sensitivity to dalbavancin: new clinical using lipoglycopeptide. We tested antibacterial activity of four novel semisynthetic lipoglycopeptides against S.aureus, expressing vanZ. Expression of vanZ decreased sensitivity of S. aureus RN4220 to three lipoglycopeptides. All glycopeptides that decreased their activity against S.aureus had lipophilic tails. This suggests, that decreased sensitivity to glycopeptides, caused by vanZ expression, may be associated with the presence of lipid tail in the structure of antibiotic.