title: Emergence of the epidemic methicillin-resistant Staphylococcus aureus strain USA300 coincides with horizontal transfer of the arginine catabolic mobile element and speG-mediated adaptations for survival on skin.
abstract: The arginine catabolic mobile element (ACME) is the largest genomic region distinguishing epidemic USA300 strains of methicillin-resistant Staphylococcus aureus (MRSA) from other S. aureus strains. However, the functional relevance of ACME to infection and disease has remained unclear. Using phylogenetic analysis, we have shown that the modular segments of ACME were assembled into a single genetic locus in Staphylococcus epidermidis and then horizontally transferred to the common ancestor of USA300 strains in an extremely recent event. Acquisition of one ACME gene, speG, allowed USA300 strains to withstand levels of polyamines (e.g., spermidine) produced in skin that are toxic to other closely related S. aureus strains. speG-mediated polyamine tolerance also enhanced biofilm formation, adherence to fibrinogen/fibronectin, and resistance to antibiotic and keratinocyte-mediated killing. We suggest that these properties gave USA300 a major selective advantage during skin infection and colonization, contributing to the extraordinary evolutionary success of this clone.
  
  
  OBJECTIVE
  Over the past 15 years, methicillin-resistant Staphylococcus aureus (MRSA) has become a major public health problem. It is likely that adaptations in specific MRSA lineages (e.g., USA300) drove the spread of MRSA across the United States and allowed it to replace other, less-virulent S. aureus strains. We suggest that one major factor in the evolutionary success of MRSA may have been the acquisition of a gene (speG) that allows S. aureus to evade the toxicity of polyamines (e.g., spermidine and spermine) that are produced in human skin. Polyamine tolerance likely gave MRSA multiple fitness advantages, including the formation of more-robust biofilms, increased adherence to host tissues, and resistance to antibiotics and killing by human skin cells.
authors.affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics, Columbia University, College of Physicians and Surgeons, New York, New York, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Planet
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: LaRussa
authors.forename: Ali
authors.initials: A
authors.lastname: Dana
authors.forename: Hannah
authors.initials: H
authors.lastname: Smith
authors.forename: Amy
authors.initials: A
authors.lastname: Xu
authors.forename: Chanelle
authors.initials: C
authors.lastname: Ryan
authors.forename: Anne-Catrin
authors.initials: AC
authors.lastname: Uhlemann
authors.forename: Sam
authors.initials: S
authors.lastname: Boundy
authors.forename: Julia
authors.initials: J
authors.lastname: Goldberg
authors.forename: Apurva
authors.initials: A
authors.lastname: Narechania
authors.forename: Ritwij
authors.initials: R
authors.lastname: Kulkarni
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Ratner
authors.forename: Joan A
authors.initials: JA
authors.lastname: Geoghegan
authors.forename: Sergios-Orestis
authors.initials: SO
authors.lastname: Kolokotronis
authors.forename: Alice
authors.initials: A
authors.lastname: Prince
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism; D001711:Biotransformation; D004269:DNA, Bacterial / Q000235:genetics; D019143:Evolution, Molecular; D022761:Gene Transfer, Horizontal; D006801:Humans; D020071:Interspersed Repetitive Sequences; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics* / Q000502:physiology*; D050296:Microbial Viability; D010802:Phylogeny; D011073:Polyamines / Q000378:metabolism*; D012867:Skin / Q000382:microbiology*; D013212:Staphylococcus epidermidis / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D011073:Polyamines