Journal article

Convergent Evolution Driven by Rifampin Exacerbates the Global Burden of Drug-Resistant &ITStaphylococcus aureus&IT

Romain Guerillot, Anders Goncalves da Silva, Ian Monk, Stefano Giulieri, Takehiro Tomita, Eloise Alison, Jessica Porter, Sacha Pidot, Wei Gao, Anton Y Peleg, Torsten Seemann, Timothy P Stinear, Benjamin P Howden



Mutations in the beta-subunit of bacterial RNA polymerase (RpoB) cause resistance to rifampin (Rifr), a critical antibiotic for treatment of multidrug-resistant Staphylococcus aureus. In vitro studies have shown that RpoB mutations confer decreased susceptibility to other antibiotics, but the clinical relevance is unknown. Here, by analyzing 7,099 S. aureus genomes, we demonstrate that the most prevalent RpoB mutations promote clinically relevant phenotypic plasticity resulting in the emergence of stable S. aureus lineages, associated with increased risk of therapeutic failure through generation of small-colony variants (SCVs) and coresistance to last-line antimicrobial agents. We found eigh..

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Awarded by National Health and Medical Research Council (NHMRC), Australia

Funding Acknowledgements

This work was supported by the National Health and Medical Research Council (NHMRC), Australia Project Grant (GNT1066791) and Research Fellowship to T.P.S. (GNT1008549) and Practitioner Fellowship to B.P.H. (GNT1105905). Doherty Applied Microbial Genomics is funded by the Department of Microbiology and Immunology of The University of Melbourne.