Proteome profile of Methicillin-Resistant Staphylococcus aureus Membrane-Derived Vesicles grown in presence of sub-MIC dosage of Vancomycin

Methicillin-resistant Staphylococcus aureus (MRSA) has evolved numerous antimicrobial resistance mechanisms and is identified as a serious public health threat by the World Health Organization and U.S. Centers for Disease Control and Prevention. The glycopeptide vancomycin (VAN) remains a cornerstone of therapy for severe MRSA infections despite increasing reports of therapeutic failure in hospitalized patients with bacteremia or pneumonia. Here we examined the effectiveness of MVs-derived methicillin-resistant SA (MRSA) to counteract vancomycin (VAN). We found that supplementation of a typical MIC assay using bacteriologic and tissue-mimicking media with purified MVs attenuated MRSA susceptibility to VAN but no other examined cell-wall targeting antibiotics. In addition, the purified MVs protected MRSA challenged with sub-therapeutic dosage of VAN against the host’s innate immune system. Additionally, the proteome of MV peptides from VAN exposed MRSA was characterized to determine if protein expression was altered.