Comprehensive genomic investigation of adaptive mutations driving the low-level oxacillin resistance phenotype in staphylococcus aureus

SG Giulieri; R Guérillot; JC Kwong; IR Monk; AS Hayes; D Daniel; S Baines; NL Sherry; NE Holmes; P Ward; W Gao; T Seemann; TP Stinear; BP Howden

Journal article

Comprehensive genomic investigation of adaptive mutations driving the low-level oxacillin resistance phenotype in staphylococcus aureus

SG Giulieri, R Guérillot, JC Kwong, IR Monk, AS Hayes, D Daniel, S Baines, NL Sherry, NE Holmes, P Ward, W Gao, T Seemann, TP Stinear, BP Howden

Mbio | AMER SOC MICROBIOLOGY | Published : 2020

DOI: 10.1128/mBio.02882-20

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Abstract

Antistaphylococcal penicillins such as oxacillin are the key antibiotics in the treatment of invasive methicillin-susceptible Staphylococcus aureus (MSSA) infec-tions; however, mec gene-independent resistance adaptation can cause treatment failure. Despite its clinical relevance, the basis of this phenomenon remains poorly understood. Here, we investigated the genomic adaptation to oxacillin at an unprec-edented scale using a large collection of 503 clinical mec-negative isolates and 30 in vitro-adapted isolates from independent oxacillin exposures. By combining compara-tive genomics, evolutionary convergence, and genome-wide association analysis, we found 21 genetic loci associated with low..

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University of Melbourne Researchers

Stefano Giulieri Author

Romain Guérillot Author

Jason Kwong Author

Ian Monk Author

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Funding Acknowledgements

This work was supported by a Research Fellowship to B.P.H. and T.P.S. from the National Health and Medical Research Council, Australia. S.G.G. was supported by a PhD scholarship of the University of Melbourne.