title: Genomic and transcriptomic differences in community acquired methicillin resistant Staphylococcus aureus USA300 and USA400 strains.
abstract: BACKGROUND
  Staphylococcus aureus is a human pathogen responsible for substantial morbidity and mortality through its ability to cause a number of human infections including bacteremia, pneumonia and soft tissue infections. Of great concern is the emergence and dissemination of methicillin-resistant Staphylococcus aureus strains (MRSA) that are resistant to nearly all β-lactams. The emergence of the USA300 MRSA genetic background among community associated S. aureus infections (CA-MRSA) in the USA was followed by the disappearance of USA400 CA-MRSA isolates.
  
  
  RESULTS
  To gain a greater understanding of the potential fitness advantages and virulence capacity of S. aureus USA300 clones, we performed whole genome sequencing of 15 USA300 and 4 USA400 clinical isolates. A comparison of representative genomes of the USA300 and USA400 pulsotypes indicates a number of differences in mobile genome elements. We examined the in vitro gene expression profiles by microarray hybridization and the in vivo transcriptomes during lung infection in mice of a USA300 and a USA400 MRSA strain by performing complete genome qRT-PCR analysis. The unique presence and increased expression of 6 exotoxins in USA300 (12- to 600-fold) compared to USA400 may contribute to the increased virulence of USA300 clones. Importantly, we also observed the up-regulation of prophage genes in USA300 (compared with USA400) during mouse lung infection (including genes encoded by both prophages ΦSa2usa and ΦSa3usa), suggesting that these prophages may play an important role in vivo by contributing to the elevated virulence characteristic of the USA300 clone.
  
  
  CONCLUSIONS
  We observed differences in the genetic content of USA300 and USA400 strains, as well as significant differences of in vitro and in vivo gene expression of mobile elements in a lung pneumonia model. This is the first study to document the global transcription differences between USA300 and USA400 strains during both in vitro and in vivo growth.
authors.affiliation: J. Craig Venter Institute, 4120 Capricorn Lane, La Jolla, CA, 92037, USA. mjones@jcvi.org.
authors.forename: Marcus B
authors.initials: MB
authors.lastname: Jones
authors.affiliation: Department of Pediatrics, Section of Critical Care, University of Chicago, Chicago, IL, 60637, USA. cmontgomery@bsd.uchicago.edu.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Montgomery
authors.affiliation: Department of Pediatrics, Section of Infectious Diseases, Chicago, IL, 60637, USA. sboyle@peds.bsd.uchicago.edu.
authors.forename: Susan
authors.initials: S
authors.lastname: Boyle-Vavra
authors.affiliation: Department of Medicine, Center for Emerging and Re-emerging Pathogens, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Rutgers University, Newark, NJ, 07103, USA. Kenneth.shatzkes@rutgers.edu.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Shatzkes
authors.affiliation: Battelle National Biodefense Institute, National Biodefense Analysis and Countermeasures Center, Frederick, MD, 21702, USA. rosslyn.maybank@nbacc.dhs.gov.
authors.forename: Rosslyn
authors.initials: R
authors.lastname: Maybank
authors.affiliation: J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, MD, 20850, USA. BFrank@jcvi.org.
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Frank
authors.affiliation: Sanford Burnham Medical Research Institute, 10901 N. Torrey Pines Rd, La Jolla, CA, 92037, USA. speterson@sanfordburnham.org.
authors.forename: Scott N
authors.initials: SN
authors.lastname: Peterson
authors.affiliation: Department of Pediatrics, Section of Critical Care, University of Chicago, Chicago, IL, 60637, USA. rdaum@peds.bsd.uchicago.edu.|Department of Pediatrics, Section of Infectious Diseases, Chicago, IL, 60637, USA. rdaum@peds.bsd.uchicago.edu.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Daum
mesh_terms: D017714:Community-Acquired Infections / Q000453:epidemiology / Q000382:microbiology*; D016680:Genome, Bacterial; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics*; D012329:RNA, Bacterial / Q000235:genetics*; D013203:Staphylococcal Infections / Q000453:epidemiology / Q000235:genetics* / Q000382:microbiology; D059467:Transcriptome; D014481:United States / Q000453:epidemiology
chemical_list: D012329:RNA, Bacterial