Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/20299
Title: Remodelling of pSK1 Family Plasmids and Enhanced Chlorhexidine Tolerance in a Dominant Hospital Lineage of Methicillin-Resistant Staphylococcus aureus.
Austin Authors: Baines, Sarah L;Jensen, Slade O;Firth, Neville;Gonçalves da Silva, Anders;Seemann, Torsten;Carter, Glen;Williamson, Deborah A;Howden, Benjamin P ;Stinear, Timothy P
Affiliation: Department of Microbiology & Immunology, The University of Melbourne at The Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology & Immunology, The University of Melbourne at The Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
School of Life and Environmental Sciences, University of Sydney, Sydney, New South Wales, Australia
Microbiology and Infectious Diseases, School of Medicine, Ingham Institute for Applied Medical Research, University of Western Sydney, Sydney, New South Wales, Australia
Doherty Applied Microbial Genomics, Department of Microbiology & Immunology, The University of Melbourne at The Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia
Issue Date: 19-Feb-2019
metadata.dc.date: 2019-04-25
Publication information: Antimicrobial agents and chemotherapy 2019; 63(5): E02356-18
Abstract: Staphylococcus aureus is a significant human pathogen whose evolution and adaptation has been shaped in part by mobile genetic elements (MGEs), facilitating global spread of extensive antimicrobial resistance. However, our understanding of the evolutionary dynamics surrounding MGEs is incomplete, in particular how changes in the structure of multidrug-resistant (MDR) plasmids may influence important staphylococcal phenotypes. Here, we undertook a population- and functional-genomics study of 212 methicillin-resistant S. aureus (MRSA) ST239 isolates collected over 32 years to explore the evolution of the pSK1 family of MDR plasmids; illustrating how these plasmids have co-evolved with and contributed to the successful adaptation of this persistent MRSA lineage. Using complete genomes and temporal phylogenomics we reconstructed the evolution of the pSK1 family lineage from its emergence in the late 1970s, with multiple structural variants arising. Plasmid maintenance and stability was linked to IS256- and IS257-mediated chromosomal integration and disruption of plasmid replication machinery. Overlaying genomic comparisons with phenotypic susceptibility data for gentamicin, trimethoprim and chlorhexidine, it appeared that pSK1 has contributed to enhanced resistance in ST239 MRSA through two mechanisms: (i) acquisition of plasmid-borne resistance mechanisms increasing rates of gentamicin resistance and reduced chlorhexidine susceptibility, and (ii) changes in plasmid configuration linked with further enhancement of chlorhexidine tolerance. While the exact mechanism of enhanced tolerance remains elusive, this research has uncovered a potential evolutionary response of ST239 MRSA to biocides, one which may contribute to the ongoing persistence and adaptation of this lineage within healthcare institutions.
URI: http://ahro.austin.org.au/austinjspui/handle/1/20299
DOI: 10.1128/AAC.02356-18
ORCID: 0000-0002-0557-0518
0000-0001-7363-6665
0000-0002-0557-0518
0000-0003-4489-589X
0000-0001-6046-610X
0000-0003-0237-1473
0000-0002-7306-9362
0000-0003-0150-123X
PubMed URL: 30783008
Type: Journal Article
Appears in Collections:Journal articles

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