Journal article

Unstable chromosome rearrangements in Staphylococcus aureus cause phenotype switching associated with persistent infections

Romain Guerillot, Xenia Kostoulias, Liam Donovan, Lucy Li, Glen P Carter, Abderrahman Hachani, Koen Vandelannoote, Stefano Giulieri, Ian R Monk, Mayu Kunimoto, Lora Starrs, Gaetan Burgio, Torsten Seemann, Anton Y Peleg, Timothy P Stinear, Benjamin P Howden

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | NATL ACAD SCIENCES | Published : 2019

Abstract

Staphylococcus aureus small-colony variants (SCVs) are associated with unusually chronic and persistent infections despite active antibiotic treatment. The molecular basis for this clinically important phenomenon is poorly understood, hampered by the instability of the SCV phenotype. Here we investigated the genetic basis for an unstable S. aureus SCV that arose spontaneously while studying rifampicin resistance. This SCV showed no nucleotide differences across its genome compared with a normal-colony variant (NCV) revertant, yet the SCV presented the hallmarks of S. aureus linked to persistent infection: down-regulation of virulence genes and reduced hemolysis and neutrophil chemotaxis, whi..

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Grants

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


Awarded by H2020-MSCA-Global Fellowship


Funding Acknowledgements

This work was supported by National Health and Medical Research Council, Australia (NHMRC) Project Grant GNT1066791 and a Research Fellowship (to T.P.S., GNT1008549) and Practitioner Fellowships (to B.P.H., GNT1105905; to A.Y.P., GNT1117940). A.H. is supported by the H2020-MSCA-Global Fellowship (Grant 657766). Doherty Applied Microbial Genomics is funded by the Department of Microbiology and Immunology at The University of Melbourne.