Abstract
Vancomycin has been the primary agent used to treat serious Methicillin-resistant Staphylococcus aureus (MRSA) infection for many years. However, the rise of MRSA infection rates and the extensive use of vancomycin have led to the emergence of reduced vancomycin susceptibility. Therefore, four typical Staphylococcus aureus (S. aureus) strains from different clinical specimens were derivated by vancomycin in vitro to better clarify their phenotypic and molecular characteristics. Some experiments, such as stepwise selection of vancomycin-resistant strains, pulsed-field gel electrophoresis (PFGE), antimicrobial susceptibility test, population analysis profile-area under the curve (PAP-AUC), molecular typing, transmission electron microscopy, δ-hemolysin expression, autolysis assay, biofilm assay and quantitative real-time polymerase chain reaction (qPCR) for gene expression were carried out to compare the derivated bacteria with their parental strains. Results showed that the observed phenotypes of vancomycin-resistant strains such as hemolysin, autolysis and biofilm significantly reduced, which were associated with vancomycin resistance capability of the selected strain. The changes of phenotype and regulatory genes expression were inversely proportional to the vancomycin minimum inhibitory concentration (MICvan). Most heterogeneous vancomycin intermediate Staphylococcus aureus (hVISA) or VISA strains belonged to spa type t570 and agr group II. In summary, the clinical isolated vancomycin susceptible Staphylococcus aureus (VSSA), hVISA and VISA could be derivated into high vancomycin-resistant VISA in vitro, but it was difficult for them to develop into vancomycin resistant Staphylococcus aureus (VRSA). VISA and hVISA could gradually adapt to the environment with the vancomycin concentration that continuously elevates.
Highlights
Vancomycin has been the primary agent used to treat serious Methicillin-resistant Staphylococcus aureus (MRSA) infection for many years
The clinical isolated vancomycin susceptible Staphylococcus aureus (VSSA), heterogeneous vancomycin intermediate Staphylococcus aureus (hVISA) and VISA could be derivated into high vancomycin-resistant VISA in vitro, but it was difficult for them to develop into vancomycin resistant Staphylococcus aureus (VRSA)
The evidence about phenotypic and molecular characterization of vancomycin-resistant S. aureus mainly come from clinical cases [33,34,35,36], the complex environment of the human body will affect the exploration of relationship between VSSA and vancomycin-resistant hVISA or VISA
Summary
Vancomycin has been the primary agent used to treat serious MRSA infection for many years. The rise of MRSA infection rates and the extensive use of vancomycin have led to the emergence of reduced vancomycin susceptibility. Vancomycin resistant S. aureus strains are associated with inefficient vancomycin treatment [1]. Nowadays more and more clinical S. aureus strains with reduced vancomycin susceptibility have been reported frequently, including hVISA and VISA [2,3,4,5,6,7]. In 2008, researchers from peking union medical college surveyed 1012 strains of MRSA collected from 14 cities in China, showed that the incidence of hVISA was between 13% and 16% [8]. Our previous studies have shown that the four-year period (2007-2010) of hVISA prevalence is from 8.2% to 11.7% in Northeast China [7]
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