title: Identification of a highly transmissible animal-independent Staphylococcus aureus ST398 clone with distinct genomic and cell adhesion properties.
abstract: A methicillin-resistant Staphylococcus aureus (MRSA) clone known as ST398 has emerged as a major cause of acute infections in individuals who have close contact with livestock. More recently, the emergence of an animal-independent ST398 methicillin-sensitive S. aureus (MSSA) clone has been documented in several countries. However, the limited surveillance of MSSA has precluded an accurate assessment of the global spread of ST398 and its clinical relevance. Here we provide evidence that ST398 is a frequent source of MSSA infections in northern Manhattan and is readily transmitted between individuals in households. This contrasts with the limited transmissibility of livestock-associated ST398 (LA-ST398) MRSA strains between humans. Our whole-genome sequence analysis revealed that the chromosome of the human-associated ST398 MSSA clone is smaller than that of the LA-ST398 MRSA reference strain S0385, due mainly to fewer mobile genetic elements (MGEs). In contrast, human ST398 MSSA isolates harbored the prophage ϕ3 and the human-specific immune evasion cluster (IEC) genes chp and scn. While most of the core genome was conserved between the human ST398 MSSA clone and S0385, these strains differed substantially in their repertoire and composition of intact adhesion genes. These genetic changes were associated with significantly enhanced adhesion of human ST398 MSSA isolates to human skin keratinocytes and keratin. We propose that the human ST398 MSSA clone can spread independent of animal contact using an optimized repertoire of MGEs and adhesion molecules adapted to transmission among humans.
  
  
  OBJECTIVE
  Staphylococcus aureus strains have generally been considered to be species specific. However, cross-species transfers of S. aureus clones, such as ST398 methicillin-resistant S. aureus (MRSA), from swine to humans have been reported. Recently, we observed the emergence of ST398 methicillin-susceptible S. aureus (MSSA) as a colonizing strain of humans in northern Manhattan. Here we report that ST398 is a frequent cause of MSSA infections in this urban setting. The ST398 MSSA clone was readily transmitted within households, independent of animal contact. We discovered that human ST398 MSSA genomes were smaller than that of the LA-ST398 strain S0385 due to fewer mobile genetic elements. Human and LA-ST398 strains also differed in their composition of adhesion genes and their ability to bind to human skin keratinocytes, providing a potential mechanism of S. aureus host adaptation. Our findings illustrate the importance of implementing molecular surveillance of MSSA given the evidence for the rapid and clinically undetected spread of ST398 MSSA.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, College of Physicians and Surgeons, Columbia University, New York, New York, USA. au2110@columbia.edu
authors.forename: Anne-Catrin
authors.initials: AC
authors.lastname: Uhlemann
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Porcella
authors.forename: Sheetal
authors.initials: S
authors.lastname: Trivedi
authors.forename: Sean B
authors.initials: SB
authors.lastname: Sullivan
authors.forename: Cory
authors.initials: C
authors.lastname: Hafer
authors.forename: Adam D
authors.initials: AD
authors.lastname: Kennedy
authors.forename: Kent D
authors.initials: KD
authors.lastname: Barbian
authors.forename: Alex J
authors.initials: AJ
authors.lastname: McCarthy
authors.forename: Craig
authors.initials: C
authors.lastname: Street
authors.forename: David L
authors.initials: DL
authors.lastname: Hirschberg
authors.forename: W Ian
authors.initials: WI
authors.lastname: Lipkin
authors.forename: Jodi A
authors.initials: JA
authors.lastname: Lindsay
authors.forename: Frank R
authors.initials: FR
authors.lastname: DeLeo
authors.forename: Franklin D
authors.initials: FD
authors.lastname: Lowy
mesh_terms: D000293:Adolescent; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001422:Bacterial Adhesion; D002648:Child; D002675:Child, Preschool; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D016680:Genome, Bacterial; D006801:Humans; D020071:Interspersed Repetitive Sequences; D015603:Keratinocytes / Q000382:microbiology; D008712:Methicillin / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009519:New York City / Q000453:epidemiology; D039002:Prophages / Q000235:genetics; D017422:Sequence Analysis, DNA; D013203:Staphylococcal Infections / Q000453:epidemiology* / Q000382:microbiology / Q000635:transmission*; D013211:Staphylococcus aureus / Q000145:classification / Q000302:isolation & purification* / Q000472:pathogenicity*; D026801:Synteny; D037521:Virulence Factors / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D016326:Extracellular Matrix Proteins; D037521:Virulence Factors; D008712:Methicillin