Virulence Gene Expression in Human Community-Acquired Staphylococcus aureus Infections

摘要

Isolates of methicillin-resistant Staphylococcus aureus (MRSA) were once linked uniformly with hospital-associated infections; however, community-acquired methicillin-resistant S. aureus (CA-MRSA) now represents an emerging threat worldwide. To examine the association of differential virulence gene expression with outcomes of human infection, we measured transcript abundance of target staphylococcal genes directly in clinical samples from children with active known or suspected CA-MRSA infections. Virulence genes encoding secreted toxins, including Panton-Valentine leukocidin, were highly expressed during superficial and invasive CA-MRSA infections. In contrast, increased expression of surface-associated Protein A was linked only with invasive disease. Comparisons to laboratory growth of corresponding clinical isolates revealed that tissue-specific expression profiles reflect activity of the staphylococcal regulator Agr during human infection. These results represent the first demonstration of staphylococcal gene expression and regulation directly in human tissue. Such analysis will help to unravel the complex interactions between CA-MRSA and its host environmental niches during disease development.