AUTHOR=Cázares-Domínguez Vicenta , Ochoa Sara A. , Cruz-Córdova Ariadnna , Rodea Gerardo E. , Escalona Gerardo , Olivares Alma L. , Olivares-Trejo José de Jesús , Velázquez-Guadarrama Norma , Xicohtencatl-Cortes Juan 

TITLE=Vancomycin modifies the expression of the agr system in multidrug-resistant Staphylococcus aureus clinical isolates

JOURNAL=Frontiers in Microbiology

VOLUME=6

YEAR=2015

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2015.00369

DOI=10.3389/fmicb.2015.00369

ISSN=1664-302X

ABSTRACT=<p><italic>Staphylococcus aureus</italic> is an opportunistic pathogen that colonizes human hosts and causes a wide variety of diseases. Two interacting regulatory systems called <italic>agr</italic> (accessory gene regulator) and <italic>sar</italic> (staphylococcal accessory regulator) are involved in the regulation of virulence factors. The aim of this study was to evaluate the effect of vancomycin on <italic>hld</italic> and <italic>spa</italic> gene expression during the exponential and post-exponential growth phases in multidrug-resistant (MDR) <italic>S. aureus</italic>.</p><p><bold>Methods:</bold> Antibiotic susceptibility was evaluated by the standard microdilution method. The phylogenetic profile was obtained by pulsed-field gel electrophoresis (PFGE). Polymorphisms of <italic>agr</italic> and SCC<italic>mec</italic> (staphylococcal cassette chromosome <italic>mec</italic>) were analyzed by multiplex polymerase chain reaction (PCR). The expression levels of <italic>hld</italic> and <italic>spa</italic> were analyzed by reverse transcription-PCR. An enzyme-linked immunosorbent assay (ELISA) was performed to detect protein A, and biofilm formation was analyzed via crystal violet staining.</p><p><bold>Results:</bold> In total, 60.60% (20/33) of <italic>S. aureus</italic> clinical isolates were MDR. Half (10/20) of the MDR <italic>S. aureus</italic> isolates were distributed in subcluster 10, with &gt;90% similarity among them. In the isolates of this subcluster, a high prevalence (100%) for the <italic>agr</italic>II and the cassette SCC<italic>mec</italic> II polymorphisms was found. Our data showed significant increases in <italic>hld</italic> expression during the post-exponential phase in the presence and absence of vancomycin. Significant increases in <italic>spa</italic> expression, protein A production and biofilm formation were observed during the post-exponential phase when the MDR <italic>S. aureus</italic> isolates were challenged with vancomycin.</p><p><bold>Conclusion:</bold> The polymorphism <italic>agr</italic>II, which is associated with nosocomial isolates, was the most prevalent polymorphism in MDR <italic>S. aureus</italic>. Additionally, under our study conditions, vancomycin modified <italic>hld</italic> and <italic>spa</italic> expression in these clinical isolates. Therefore, vancomycin may regulate alternative systems that jointly participate in the regulation of these virulence factors.</p>