Genomic insights on heterogeneous resistance to vancomycin and teicoplanin in Methicillin-resistant Staphylococcus aureus: A first report from South India

Autoři: Yamuna Devi Bakthavatchalam aff001;  Priyanka Babu aff001;  Elakkiya Munusamy aff001;  Hariharan Triplicane Dwarakanathan aff002;  Priscilla Rupali aff003;  Marcus Zervos aff004;  Peter John Victor aff005;  Balaji Veeraraghavan aff001
Působiště autorů: Department of Clinical Microbiology, Christian Medical College, Vellore, India aff001;  Department of Orthopaedics, Christian Medical College, Vellore, India aff002;  Infectious Diseases Training and Research Center (IDTRC), Christian Medical College, Vellore, India aff003;  Infectious Diseases, Henry Ford Health System, Detroit, Michigan, United States of America aff004;  Department of critical care unit, Christian Medical College, Vellore, India aff005
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article


Methicillin-resistant Staphylococcus aureus (MRSA) infection is an important clinical concern in patients, and is often associated with significant disease burden and metastatic infections. There is an increasing evidence of heterogeneous vancomycin-intermediate S. aureus (hVISA) associated treatment failure. In this study, we aim to understand the molecular mechanism of teicoplanin resistant MRSA (TR-MRSA) and hVISA. A total of 482 MRSA isolates were investigated for these phenotypes. Of the tested isolates, 1% were identified as TR-MRSA, and 12% identified as hVISA. A highly diverse amino acid substitution was observed in tcaRAB, vraSR, and graSR genes in TR-MRSA and hVISA strains. Interestingly, 65% of hVISA strains had a D148Q mutation in the graR gene. However, none of the markers were reliable in differentiating hVISA from TR-MRSA. Significant pbp2 upregulation was noted in three TR-MRSA strains, which had teicoplanin MICs of 16 or 32 μg/ml, whilst significant pbp4 downregulation was not noted in these strains. In our study, multiple mutations were identified in the candidate genes, suggesting a complex evolutionary pathway involved in the development of TR-MRSA and hVISA strains.

Klíčová slova:

Amino acid substitution – Cell walls – Methicillin-resistant Staphylococcus aureus – Mutation detection – Staphylococcus aureus – Substitution mutation – Vancomycin – Autolysis


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