title: Rapid Emergence and Evolution of Staphylococcus aureus Clones Harboring fusC-Containing Staphylococcal Cassette Chromosome Elements.
abstract: The prevalence of fusidic acid (FA) resistance amongStaphylococcus aureusstrains in New Zealand (NZ) is among the highest reported globally, with a recent study describing a resistance rate of approximately 28%. Three FA-resistantS. aureusclones (ST5 MRSA, ST1 MSSA, and ST1 MRSA) have emerged over the past decade and now predominate in NZ, and in all three clones FA resistance is mediated by thefusCgene. In particular, ST5 MRSA has rapidly become the dominant MRSA clone in NZ, although the origin of FA-resistant ST5 MRSA has not been explored, and the genetic context offusCin FA-resistant NZ isolates is unknown. To better understand the rapid emergence of FA-resistantS. aureus, we used population-based comparative genomics to characterize a collection of FA-resistant and FA-susceptible isolates from NZ. FA-resistant NZ ST5 MRSA displayed minimal genetic diversity and represented a phylogenetically distinct clade within a global population model of clonal complex 5 (CC5)S. aureus In all lineages,fusCwas invariably located within staphylococcal cassette chromosome (SCC) elements, suggesting that SCC-mediated horizontal transfer is the primary mechanism offusCdissemination. The genotypic association offusCwithmecAhas important implications for the emergence of MRSA clones in populations with high usage of fusidic acid. In addition, we found thatfusCwas colocated with a recently described virulence factor (tirS) in dominant NZS. aureusclones, suggesting a fitness advantage. This study points to the likely molecular mechanisms responsible for the successful emergence and spread of FA-resistantS. aureus.
authors: Doherty Applied Microbial Genomics, Department of Microbiology & Immunology, The University of Melbourne at The Doherty Institute for Infection and Immunity, Melbourne, Australia Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology & Immunology, The University of Melbourne at The Doherty Institute for Infection and Immunity, Melbourne, Australia.
authors: Sarah L
authors: SL
authors: Baines
authors: Doherty Applied Microbial Genomics, Department of Microbiology & Immunology, The University of Melbourne at The Doherty Institute for Infection and Immunity, Melbourne, Australia Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology & Immunology, The University of Melbourne at The Doherty Institute for Infection and Immunity, Melbourne, Australia Infectious Diseases Department, Austin Health, Melbourne, Australia.
authors: Benjamin P
authors: BP
authors: Howden
authors: Institute of Environmental Science and Research, Wellington, New Zealand.
authors: Helen
authors: H
authors: Heffernan
authors: Doherty Applied Microbial Genomics, Department of Microbiology & Immunology, The University of Melbourne at The Doherty Institute for Infection and Immunity, Melbourne, Australia Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology & Immunology, The University of Melbourne at The Doherty Institute for Infection and Immunity, Melbourne, Australia.
authors: Timothy P
authors: TP
authors: Stinear
authors: Doherty Applied Microbial Genomics, Department of Microbiology & Immunology, The University of Melbourne at The Doherty Institute for Infection and Immunity, Melbourne, Australia Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology & Immunology, The University of Melbourne at The Doherty Institute for Infection and Immunity, Melbourne, Australia.
authors: Glen P
authors: GP
authors: Carter
authors: Doherty Applied Microbial Genomics, Department of Microbiology & Immunology, The University of Melbourne at The Doherty Institute for Infection and Immunity, Melbourne, Australia Victorian Life Sciences Computation Initiative, The University of Melbourne, Melbourne, Australia.
authors: Torsten
authors: T
authors: Seemann
authors: Doherty Applied Microbial Genomics, Department of Microbiology & Immunology, The University of Melbourne at The Doherty Institute for Infection and Immunity, Melbourne, Australia Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology & Immunology, The University of Melbourne at The Doherty Institute for Infection and Immunity, Melbourne, Australia Infectious Diseases Department, Austin Health, Melbourne, Australia.
authors: Jason C
authors: http://orcid.org/0000-0002-6298-7942
authors: JC
authors: Kwong
authors: School of Medical Sciences, University of Auckland, Auckland, New Zealand.
authors: Stephen R
authors: SR
authors: Ritchie
authors: Doherty Applied Microbial Genomics, Department of Microbiology & Immunology, The University of Melbourne at The Doherty Institute for Infection and Immunity, Melbourne, Australia Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology & Immunology, The University of Melbourne at The Doherty Institute for Infection and Immunity, Melbourne, Australia Institute of Environmental Science and Research, Wellington, New Zealand deborah.williamson@unimelb.edu.au.
authors: Deborah A
authors: DA
authors: Williamson
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002876:Chromosomes, Bacterial / Q000737:chemistry*; D060965:Clonal Evolution; D002999:Clone Cells; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D005672:Fusidic Acid / Q000494:pharmacology*; D015870:Gene Expression; D022761:Gene Transfer, Horizontal; D014644:Genetic Variation; D006801:Humans; D008826:Microbial Sensitivity Tests; D058885:Multilocus Sequence Typing; D009520:New Zealand / Q000453:epidemiology; D046915:Penicillin-Binding Proteins / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D015995:Prevalence; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D046915:Penicillin-Binding Proteins; D037521:Virulence Factors; C487789:mecA protein, Staphylococcus aureus; D005672:Fusidic Acid