Rifaximin prophylaxis causes resistance to the last-resort antibiotic daptomycin

AM Turner; L Li; IR Monk; JYH Lee; DJ Ingle; S Portelli; NL Sherry; N Isles; T Seemann; LK Sharkey; CJ Walsh; GE Reid; S Nie; BA Eijkelkamp; NE Holmes; B Collis; S Vogrin; A Hiergeist; D Weber; A Gessner; E Holler; DB Ascher; S Duchene; NE Scott; TP Stinear; JC Kwong; CL Gorrie; BP Howden; GP Carter

Journal article

Rifaximin prophylaxis causes resistance to the last-resort antibiotic daptomycin

AM Turner, L Li, IR Monk, JYH Lee, DJ Ingle, S Portelli, NL Sherry, N Isles, T Seemann, LK Sharkey, CJ Walsh, GE Reid, S Nie, BA Eijkelkamp, NE Holmes, B Collis, S Vogrin, A Hiergeist, D Weber, A Gessner Show all

Nature | NATURE PORTFOLIO | Published : 2024

DOI: 10.1038/s41586-024-08095-4

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Abstract

Multidrug-resistant bacterial pathogens like vancomycin-resistant Enterococcus faecium (VREfm) are a critical threat to human health1. Daptomycin is a last-resort antibiotic for VREfm infections with a novel mode of action2, but for which resistance has been widely reported but is unexplained. Here we show that rifaximin, an unrelated antibiotic used prophylactically to prevent hepatic encephalopathy in patients with liver disease3, causes cross-resistance to daptomycin in VREfm. Amino acid changes arising within the bacterial RNA polymerase in response to rifaximin exposure cause upregulation of a previously uncharacterized operon (prdRAB) that leads to cell membrane remodelling and cross-r..

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University of Melbourne Researchers

Lucy Li Author

Ian Monk Author

Jean Lee Author

Danielle Ingle Author

Related Projects (2)

THE METAFIND (METAGENOMICS FOR INFECTIOUS DISEASES) PROJECT: DEVELOPING CLINICAL METAGENOMICSTO IMPROVE THE HEALTHCARE OF PATIENTS WITH INFECTIONS

The MetaFIND (Metagenomics For INfectious Diseases) project is a combined laboratory and clinical study that aims to develop and investigate..

UNDERSTANDING THE MECHANISMS OF GASTROINTESTINAL COLONISATION WITH VANCOMYCIN-RESISTANT ENTEROCOCCUS FAECIUM (VRE)

This project will use state-of-the-art molecular biology to understand how the superbug vancomycin-resistant Enterococcus (VRE) colonises pa..

Grants

Awarded by State Government of Victoria

Funding Acknowledgements

This work was supported by a National Health and Medical Research Council (NHMRC) of Australia Ideas grant (GNT1185213) to G.P.C., C.L.G. and I.R.M., and NHMRC project grant (GNT1160745) to B.P.H., T.P.S. and G.P.C. T.P.S. was supported by an NHMRC Investigator grant (GNT1194325). G.P.C. was supported by a University of Melbourne MDHS (Medicine, Dentistry and Health Sciences) mid-career seeding ideas grant and B.P.H. by an NHMRC Investigator Grant (GNT1196103). J.C.K. is supported by an NHMRC Early Career Fellowship (GNT1142613). A.M.T. and N.L.S. are supported by an Australian Government Research Training Program scholarship. D.J.I. is supported by an NHMRC Investigator Grant (GNT1195210). S.D. is supported by the Inception program (Investissement d'Avenir grant ANR-16-CONV-0005), an Investigator grant from the NHMRC (GNT2017284), and the Australian Research Council (FT220100629). The Controlling Superbugs study was supported by the Melbourne Genomics Health Alliance (funded by the State Government of Victoria, Department of Health and Human Services and the ten member organizations). N.E.S. is supported by an Australian Research Council Future Fellowship (FT200100270) and an ARC Discovery Project Grant (DP210100362). This study was also supported by Deutsche Forschungsgemeinschaft Projektnummer (324392634 - TRR 221 B13) to A.G., E.H. and D.W. We thank the staff at the Melbourne Mass Spectrometry and Proteomics Facility of The Bio21 Molecular Science and Biotechnology Institute for access to MS instrumentation and staff within the Microbiological Diagnostic Unit Public Health Laboratory for technical assistance with antimicrobial susceptibility testing and WGS.