title: Subtle genetic changes enhance virulence of methicillin resistant and sensitive Staphylococcus aureus.
abstract: BACKGROUND
  Community acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) increasingly causes disease worldwide. USA300 has emerged as the predominant clone causing superficial and invasive infections in children and adults in the USA. Epidemiological studies suggest that USA300 is more virulent than other CA-MRSA. The genetic determinants that render virulence and dominance to USA300 remain unclear.
  
  
  RESULTS
  We sequenced the genomes of two pediatric USA300 isolates: one CA-MRSA and one CA-methicillin susceptible (MSSA), isolated at Texas Children's Hospital in Houston. DNA sequencing was performed by Sanger dideoxy whole genome shotgun (WGS) and 454 Life Sciences pyrosequencing strategies. The sequence of the USA300 MRSA strain was rigorously annotated. In USA300-MRSA 2658 chromosomal open reading frames were predicted and 3.1 and 27 kilobase (kb) plasmids were identified. USA300-MSSA contained a 20 kb plasmid with some homology to the 27 kb plasmid found in USA300-MRSA. Two regions found in US300-MRSA were absent in USA300-MSSA. One of these carried the arginine deiminase operon that appears to have been acquired from S. epidermidis. The USA300 sequence was aligned with other sequenced S. aureus genomes and regions unique to USA300 MRSA were identified.
  
  
  CONCLUSIONS
  USA300-MRSA is highly similar to other MRSA strains based on whole genome alignments and gene content, indicating that the differences in pathogenesis are due to subtle changes rather than to large-scale acquisition of virulence factor genes. The USA300 Houston isolate differs from another sequenced USA300 strain isolate, derived from a patient in San Francisco, in plasmid content and a number of sequence polymorphisms. Such differences will provide new insights into the evolution of pathogens.
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA. sarahh@bcm.edu
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Highlander
authors.forename: Kristina G
authors.initials: KG
authors.lastname: Hultén
authors.forename: Xiang
authors.initials: X
authors.lastname: Qin
authors.forename: Huaiyang
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authors.lastname: Jiang
authors.forename: Shailaja
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authors.lastname: Yerrapragada
authors.forename: Edward O
authors.initials: EO
authors.lastname: Mason
authors.forename: Yue
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authors.lastname: Shang
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Williams
authors.forename: Régine M
authors.initials: RM
authors.lastname: Fortunov
authors.forename: Yamei
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authors.lastname: Liu
authors.forename: Okezie
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authors.lastname: Igboeli
authors.forename: Joseph
authors.initials: J
authors.lastname: Petrosino
authors.forename: Madhan
authors.initials: M
authors.lastname: Tirumalai
authors.forename: Akif
authors.initials: A
authors.lastname: Uzman
authors.forename: George E
authors.initials: GE
authors.lastname: Fox
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Cardenas
authors.forename: Donna M
authors.initials: DM
authors.lastname: Muzny
authors.forename: Lisa
authors.initials: L
authors.lastname: Hemphill
authors.forename: Yan
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authors.lastname: Ding
authors.forename: Shannon
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authors.lastname: Dugan
authors.forename: Peter R
authors.initials: PR
authors.lastname: Blyth
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Buhay
authors.forename: Huyen H
authors.initials: HH
authors.lastname: Dinh
authors.forename: Alicia C
authors.initials: AC
authors.lastname: Hawes
authors.forename: Michael
authors.initials: M
authors.lastname: Holder
authors.forename: Christie L
authors.initials: CL
authors.lastname: Kovar
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Lee
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.forename: Lynne V
authors.initials: LV
authors.lastname: Nazareth
authors.forename: Qiaoyan
authors.initials: Q
authors.lastname: Wang
authors.forename: Jianling
authors.initials: J
authors.lastname: Zhou
authors.forename: Sheldon L
authors.initials: SL
authors.lastname: Kaplan
authors.forename: George M
authors.initials: GM
authors.lastname: Weinstock
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001483:Base Sequence; D044404:Genomic Islands / Q000235:genetics; D006801:Humans; D006867:Hydrolases / Q000235:genetics; D016106:Methicillin Resistance; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D011110:Polymorphism, Genetic; D013203:Staphylococcal Infections / Q000453:epidemiology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics*; D014481:United States / Q000453:epidemiology
chemical_list: D000900:Anti-Bacterial Agents; D006867:Hydrolases; C019723:arginine deiminase