AUTHOR=Vimberg Vladimir , Zieglerová Leona , Buriánková Karolína , Branny Pavel , Balíková Novotná Gabriela 

TITLE=VanZ Reduces the Binding of Lipoglycopeptide Antibiotics to Staphylococcus aureus and Streptococcus pneumoniae Cells

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.00566

DOI=10.3389/fmicb.2020.00566

ISSN=1664-302X

ABSTRACT=<p><italic>vanZ</italic>, a member of the <italic>VanA</italic> glycopeptide resistance gene cluster, confers resistance to lipoglycopeptide antibiotics independent of cell wall precursor modification by the <italic>vanHAX</italic> genes. Orthologs of <italic>vanZ</italic> are present in the genomes of many clinically relevant bacteria, including <italic>Enterococcus faecium</italic> and <italic>Streptococcus pneumoniae</italic>; however, <italic>vanZ</italic> genes are absent in <italic>Staphylococcus aureus</italic>. Here, we show that the expression of enterococcal <italic>vanZ</italic> paralogs in <italic>S. aureus</italic> increases the minimal inhibitory concentrations of lipoglycopeptide antibiotics teicoplanin, dalbavancin, oritavancin and new teicoplanin pseudoaglycone derivatives. The reduction in the binding of fluorescently labeled teicoplanin to the cells suggests the mechanism of VanZ-mediated resistance. In addition, using a genomic <italic>vanZ</italic> gene knockout mutant of <italic>S. pneumoniae</italic>, we have shown that the ability of VanZ proteins to compromise the activity of lipoglycopeptide antibiotics by reducing their binding is a more general feature of VanZ-superfamily proteins.</p>