Emergence of the Epidemic Methicillin-Resistant Staphylococcus aureus Strain USA300 Coincides with Horizontal Transfer of the Arginine Catabolic Mobile Element and <i>speG</i> -mediated Adaptations for Survival on Skin
-
- 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
-
- Howard A. Shuman
- editor
説明
<jats:title>ABSTRACT</jats:title> <jats:p> The arginine catabolic mobile element (ACME) is the largest genomic region distinguishing epidemic USA300 strains of methicillin-resistant <jats:named-content content-type="genus-species">Staphylococcus aureus</jats:named-content> (MRSA) from other <jats:named-content content-type="genus-species">S. aureus</jats:named-content> 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 <jats:named-content content-type="genus-species">Staphylococcus epidermidis</jats:named-content> and then horizontally transferred to the common ancestor of USA300 strains in an extremely recent event. Acquisition of one ACME gene, <jats:italic>speG</jats:italic> , allowed USA300 strains to withstand levels of polyamines (e.g., spermidine) produced in skin that are toxic to other closely related <jats:named-content content-type="genus-species">S. aureus</jats:named-content> strains. <jats:italic>speG</jats:italic> -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. </jats:p> <jats:p> <jats:bold>IMPORTANCE</jats:bold> Over the past 15 years, methicillin-resistant <jats:named-content content-type="genus-species">Staphylococcus aureus</jats:named-content> (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 <jats:named-content content-type="genus-species">S. aureus</jats:named-content> strains. We suggest that one major factor in the evolutionary success of MRSA may have been the acquisition of a gene ( <jats:italic>speG</jats:italic> ) that allows <jats:named-content content-type="genus-species">S. aureus</jats:named-content> 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. </jats:p>
収録刊行物
-
- mBio
-
mBio 4 (6), e00889-13-, 2013-12-31
American Society for Microbiology