TY - JOUR
T1 - Virulence gene expression in human community-acquired Staphylococcus aureus infection
AU - Loughman, Jennifer A.
AU - Fritz, Stephanie A.
AU - Storch, Gregory A.
AU - Hunstad, David A.
N1 - Funding Information:
Financial support: National Institutes of Health (grant K08-DK067894); National Research Service Award Institutional Research Training Grant (T32-HD007507); Washington University Child Health Research Center (K12-HD01487) and Infectious Diseases Scholars Program; W. M. Keck Postdoctoral Program in Molecular Medicine.
PY - 2009/2/1
Y1 - 2009/2/1
N2 - Isolates of methicillin-resistant Staphylococcus aureus (MRSA) were once linked uniformly with hospital-associated infections; however, community-acquired MRSA (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 levels 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 with laboratory-grown corresponding clinical isolates revealed that tissue-specific expression profiles reflect the activity of the staphylococcal accessory gene regulator 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.
AB - Isolates of methicillin-resistant Staphylococcus aureus (MRSA) were once linked uniformly with hospital-associated infections; however, community-acquired MRSA (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 levels 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 with laboratory-grown corresponding clinical isolates revealed that tissue-specific expression profiles reflect the activity of the staphylococcal accessory gene regulator 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.
UR - http://www.scopus.com/inward/record.url?scp=58849131103&partnerID=8YFLogxK
U2 - 10.1086/595982
DO - 10.1086/595982
M3 - Article
C2 - 19115951
AN - SCOPUS:58849131103
SN - 0022-1899
VL - 199
SP - 294
EP - 301
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 3
ER -