Community-Acquired Methicillin Resistant Staphylococcus aureus:Effects Of Subinhibitory Concentrations of Antibiotics on the Proteome Profile USA300. Pathogeneses and susceptibility

Abstract

Staphylococcus aureus is a causative agent of many severe infections in the health care setting. Strains of increased virulence such as the community acquired methicillin-resistant S. aureus (CA-MRSA), USA300 clone, have recently emerged and have the ability to infect even healthy individuals and are difficult to treat. This report addresses the response of USA300 clone to two subinhibitory concentrations (0.25 and 0.5MICs) of four clinically relevant antibiotics, linezolid, tigecycline, oxacillin and vancomycin, by using MS/MS-proteomics approach, which let us the analyses the 980 differentially expressed proteins by bioinformatics studies. This study enables a comprehensive overview of the proteome of this hypervirulent and resistance CA-MRSA-USA300 clone, and its response to antibiotic pressure. Unlike previous genome-wide transcriptome studies where it monitored changes on mRNA but not on protein level that directly reflect physiologically relevant adaptations. We focused on several groups of main proteins associated to mechanism of action of antibiotics (including mechanism of resistance) an pathogenesis. Here, we provide evidence at the proteome adaptation of USA300 independently of the mechanism of action of every antibiotic and the possible therapeutic effect on the USA300 of higher subinhibitory concentrations of several clinical used antibiotics. The higher subinhibitory (0.5MIC) concentrations appeared to be effective. According to their effects on the proteins involved in pathogenesis proteins, the vancomycin showed to be the less effective and the tigecycline the most effective. Tigecycline got to down-regulated the expression of the main virulence factor α-haemolysin Hla. The contrary, oxacillin up-regulated the expression of the virulence factor involved in the pathogenesis phenol-soluble-modulins (PSM) and panton-valentine-leukocidin (PVL) subunit F Luk-F . Overview, the USA300 clone is able to adapt itself to antibiotic pressure of subinhibitory concentrations, trying to maintain the necessary proteins to its "alive", such as mechanism of resistance and virulence proteins, at the same time that increase the stress response after exposition the antibiotic pressure.