Emergence of the Epidemic Methicillin-Resistant <named-content content-type="genus-species">Staphylococcus aureus</named-content> Strain USA300 Coincides with Horizontal Transfer of the Arginine Catabolic Mobile Element and <italic toggle="yes">speG</italic>-mediated Adaptations for Survival on Skin
Paul J. Planet,
Samuel J. LaRussa,
Ali Dana,
Hannah Smith,
Amy Xu,
Chanelle Ryan,
Anne-Catrin Uhlemann,
Sam Boundy,
Julia Goldberg,
Apurva Narechania,
Ritwij Kulkarni,
Adam J. Ratner,
Joan A. Geoghegan,
Sergios-Orestis Kolokotronis,
Alice Prince
Affiliations
Paul J. Planet
Division of Pediatric Infectious Diseases, Department of Pediatrics, Columbia University, College of Physicians and Surgeons, New York, New York, USA
Samuel J. LaRussa
Division of Pediatric Infectious Diseases, Department of Pediatrics, Columbia University, College of Physicians and Surgeons, New York, New York, USA
Ali Dana
Department of Dermatology, James J. Peters Veterans Affairs Medical Center, Bronx, New York, USA
Hannah Smith
Division of Pediatric Infectious Diseases, Department of Pediatrics, Columbia University, College of Physicians and Surgeons, New York, New York, USA
Amy Xu
Division of Pediatric Infectious Diseases, Department of Pediatrics, Columbia University, College of Physicians and Surgeons, New York, New York, USA
Chanelle Ryan
Division of Pediatric Infectious Diseases, Department of Pediatrics, Columbia University, College of Physicians and Surgeons, New York, New York, USA
Anne-Catrin Uhlemann
Department of Internal Medicine, Division of Infectious Diseases, Columbia University, College of Physicians and Surgeons, New York, New York, USA
Sam Boundy
Department of Internal Medicine, Division of Infectious Diseases, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
Julia Goldberg
Division of Pediatric Infectious Diseases, Department of Pediatrics, Columbia University, College of Physicians and Surgeons, New York, New York, USA
Apurva Narechania
Sackler Institute for Comparative Genomics, American Museum of Natural History, New York, New York, USA
Ritwij Kulkarni
Division of Pediatric Infectious Diseases, Department of Pediatrics, Columbia University, College of Physicians and Surgeons, New York, New York, USA
Adam J. Ratner
Division of Pediatric Infectious Diseases, Department of Pediatrics, Columbia University, College of Physicians and Surgeons, New York, New York, USA
Joan A. Geoghegan
Department of Microbiology, Moyne Institute of Preventive Medicine, Trinity College, Dublin, Ireland
Sergios-Orestis Kolokotronis
Sackler Institute for Comparative Genomics, American Museum of Natural History, New York, New York, USA
Alice Prince
Division of Pediatric Infectious Diseases, Department of Pediatrics, Columbia University, College of Physicians and Surgeons, New York, New York, USA
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. IMPORTANCE 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.
