Journal article

RNase III-CLASH of multi-drug resistant Staphylococcus aureus reveals a regulatory mRNA 3′UTR required for intermediate vancomycin resistance

DG Mediati, JL Wong, W Gao, S McKellar, CNI Pang, S Wu, W Wu, B Sy, IR Monk, JM Biazik, MR Wilkins, BP Howden, TP Stinear, S Granneman, JJ Tree

Nature Communications | NATURE PORTFOLIO | Published : 2022

Abstract

Treatment of methicillin-resistant Staphylococcus aureus infections is dependent on the efficacy of last-line antibiotics including vancomycin. Treatment failure is commonly linked to isolates with intermediate vancomycin resistance (termed VISA). These isolates have accumulated point mutations that collectively reduce vancomycin sensitivity, often by thickening the cell wall. Changes in regulatory small RNA expression have been correlated with antibiotic stress in VISA isolates however the functions of most RNA regulators is unknown. Here we capture RNA–RNA interactions associated with RNase III using CLASH. RNase III-CLASH uncovers hundreds of novel RNA–RNA interactions in vivo allowing fu..

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Grants

Awarded by Australian Government


Funding Acknowledgements

pICS3 and pCN33::P<INF>tufA</INF>-gyrB::gfp vectors were a kind gift from Brice Felden (Universite de Rennes). The CRISPRi knockdown pSD1 vector was a kind gift from Baolin Sun (University of Science and Technology of China). S.G. was supported by Medical Research Council Non-Clinical Senior Research Fellowship (MR/R008205/1). S.W.M. was supported by the Wellcome Trust (109093/Z/15/A). D.G.M., B.M.S., and J.J.T. are supported by grants from the National Health and Medical Research Council, Australia (GNT1139313 and GNT1161161). S.W. and W.W. are supported by Research Training Programme Scholarships from the Australian Government.