Comprehensive Genomic Investigation of Adaptive Mutations Driving the Low-Level Oxacillin Resistance Phenotype in Staphylococcus aureus
Stefano G Giulieri, Romain Guerillot, Jason C Kwong, Ian R Monk, Ashleigh S Hayes, Diane Daniel, Sarah Baines, Norelle L Sherry, Natasha E Holmes, Peter Ward, Wei Gao, Torsten Seemann, Timothy P Stinear, Benjamin P Howden
MBIO | AMER SOC MICROBIOLOGY | Published : 2020
Antistaphylococcal penicillins such as oxacillin are the key antibiotics in the treatment of invasive methicillin-susceptible Staphylococcus aureus (MSSA) infections; 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 unprecedented scale using a large collection of 503 clinical mec-negative isolates and 30 in vitro-adapted isolates from independent oxacillin exposures. By combining comparative genomics, evolutionary convergence, and genome-wide association analysis, we found 21 genetic loci associated with low-le..View full abstract
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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.