Clonal Complex 398 Methicillin Susceptible <i>Staphylococcus aureus</i>: A Frequent Unspecialized Human Pathogen with Specific Phenotypic and Genotypic Characteristics

<div><p>Clonal complex 398 livestok-associated-MRSA (CC398 LA-MRSA) clone is described as a major animal pathogen that can also colonize and infect humans. CC398 methicillin susceptible <i>Staphylococcus aureus</i> (CC398 MSSA) is less described. We identified 126 CC398 MSSA strains of human origin within 6380 <i>S. aureus</i> isolates gathered between 2009 and 2011, from the French National Reference Centre for Staphylococci. They were characterized using antimicrobial susceptibility testing, <i>spa</i> typing, DNA microarrays (Identibac <i>S. aureus</i> Genotyping ®, Alere), CC398-specific sequence PCR, <i>erm</i>T (encoding macrolides résistance) PCR. Fifty-three CC398 LA-MRSA collected from French pigs and veal were used as comparators, and phylogenetic relations between human CC398 MSSA and animal CC398 MRSA populations were explored on the basis of <i>spa</i>-typing and DNA microarrays. CC398 MSSA were able to induce a large spectrum of infections (especially skin, bloodstream, and pneumonias). The prevalence rate of this clone was high in MSSA population, i.e., 24.7% in a local prospective study on nasal colonization, and 7.5% in a national prospective study on infective endocarditis. CC398 MSSA isolates were frequently (89%) erythromycin resistant, due to the presence of the <i>erm</i>T gene, a gene not detected in erythromycin resistant CC398 LA-MRSA strains. Expression of staphylococcal complement inhibitor (<i>scn</i>) and the chemotaxis inhibitory protein (<i>chp)</i>, was also specific to this population. The CC398 MRSA signature included also a panel of antibiotic resistance genes, especially a type IV or V cassette <i>mec</i> and <i>tetM</i>. CC398 MSSA and CC398 LA-MRSA populations were closely related based on <i>spa</i>-typing and DNA microarrays, with the MRSA strains forming the most derived lineage in phylogenic trees. Both MSSA and MRSA populations may come from common ancestors, which would have evolved in the settings of different selective pressures, explaining the acquisition of <i>ermT</i>, <i>chp</i> and <i>scn</i> for MSSA, and antibiotic resistance genes for MRSA.</p>