Journal article
Antibiotic resistance and host immune evasion in Staphylococcus aureus mediated by a metabolic adaptation
JH Jiang, MS Bhuiyan, HH Shen, DR Cameron, TWT Rupasinghe, CM Wu, AP Le Brun, X Kostoulias, C Domene, AJ Fulcher, MJ McConville, BP Howden, GJ Lieschke, AY Peleg
Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2019
Abstract
Staphylococcus aureus is a notorious human bacterial pathogen with considerable capacity to develop antibiotic resistance. We have observed that human infections caused by highly drug-resistant S. aureus are more prolonged, complicated, and difficult to eradicate. Here we describe a metabolic adaptation strategy used by clinical S. aureus strains that leads to resistance to the last-line antibiotic, daptomycin, and simultaneously affects host innate immunity. This response was characterized by a change in anionic membrane phospholipid composition induced by point mutations in the phospholipid biosynthesis gene, cls2, encoding cardiolipin synthase. Single cls2 point mutations were sufficient ..
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Awarded by CASS Foundation
Awarded by Australian National Health and Medical Research Council (NHMRC)
Awarded by Australian Research Council
Funding Acknowledgements
We thank Monash Micro Imaging for the scientific and technical assistance and the Australian Center for Neutron Scattering, Australian Nuclear Science and Technology Organization, for providing the neutron research facilities. We also acknowledge Professors George Eliopoulos and the late Robert C. Moellering, Jr., for their initial contribution of strains and mentorship. We acknowledge funding for this work from Australian National Health and Medical Research Council (NHMRC) Project Grant APP1144303 (to A. Y.P.), and CASS Foundation Grant SM/12/4276 (to A.Y.P.). A.Y.P. and B.P.H. were funded by an NHMRC Practitioner Fellowship, and H.-H.S. was funded by an NHMRC Career Development Fellowship. G.J.L. is an NHMRC Senior Research Fellow. M.J.M. is an NHMRC Principal Research Fellow. The Abberior stimulated emission depletion microscope was funded by Australian Research Council Linkage Infrastructure, Equipment and Facilities Grant LE150100110, 2015. The Australian Regenerative Medicine Institute is supported by grants from the State Government of Victoria and the Australian Government.