Sheetal Genomic and Cell Adhesion Properties ST 398 Clone with Distinct aureus Staphylococcus Animal-Independent Identification of a Highly Transmissible

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 3 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. IMPORTANCE 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. Received 30 January 2012 Accepted 3 February 2012 Published 28 February 2012 Citation Uhlemann A, et al. 2012. Identification of a highly transmissible animal-independent Staphylococcus aureus ST398 clone with distinct genomic and cell adhesion properties. mBio 3(2):e00027-12. doi:10.1128/mBio.00027-12. Editor Donald Low, Mt. Sinai Hospital Copyright © 2012 Uhlemann et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited. Address correspondence to Anne-Catrin Uhlemann, au2110@columbia.edu. Staphylococcus aureus is a highly adaptable commensal organism and an important pathogen of humans and animals (1, 2). Molecular epidemiology studies suggest that genetic subsets of S. aureus lineages are particularly well suited to causing infections in certain animal species (3, 4). Recently, swine have been identified as a major reservoir for methicillin-resistant S. aureus (MRSA) (5). Most of these MRSA strains belong to the multilocus sequence type (MLST) 398 (ST398), are nontypeable by SmaI restriction in pulsed-field gel electrophoresis (6), and can be identified by an ST398-specific restriction-modification (RM) test (7). Importantly, ST398 MRSA strains are also responsible for a significant number of acute infections, primarily in individuals who have direct contact with animals (8). ST398 was first recognized in France (8) and has been noted to cause a substantial number of MRSA infections in The Netherlands and other parts of Europe (9). This strain has now also been detected in China (10) and North America (11). The spectrum of disease most commonly includes superficial skin and soft tissue infections; however, invasive infections, such as pneumonia (12), bacteremia, and endocarditis, have also been reported (13). RESEARCH ARTICLE March/April 2012 Volume 3 Issue 2 e00027-12 ® mbio.asm. org 1 m b.asm . rg on M arch 8, 2012 P ubished by m b.asm . rg D ow nladed fom