Journal
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
Volume 2, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcimb.2012.00064
Keywords
alpha-toxin; Staphylococcus aureus; biofilm; epithelium; vaginal mucosa; toxic shock syndrome
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Funding
- National Institutes of Health, National Institute of Allergy and Infectious Diseases [AI-73366, AI-74283]
- National Science Council, Taiwan [101-2320-B-037-021]
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Staphylococcus aureus causes many diseases in humans, ranging from mild skin infections to serious, life-threatening, superantigen-mediated Toxic Shock Syndrome (TSS). S. aureus may be asymptomatically carried in the anterior nares or vagina or on the skin, serving as a reservoir for infection. Pulsed-field gel electrophoresis clonal type USA200 is the most widely disseminated colonizer and the leading cause of TSS. The cytolysin alpha-toxin (also known as alpha-hemolysin or Hla) is the major epithelial proinflammatory exotoxin produced by TSS S. aureus USA200 isolates. The current study aims to characterize the differences between TSS USA200 strains [high (hla(+)) and low (hla(-)) alpha-toxin producers] in their ability to disrupt vaginal mucosal tissue and to characterize the subsequent infection. Tissue viability post-infection and biofilm formation of TSS USA200 isolates CDC587 and MN8, which contain the alpha-toxin pseudogene MNPE (hla+), and MNPE isogenic hla knockout (hlaKO), were observed via LIVE/DEAD (R) staining and confocal microscopy. AMISS strains grew to similar bacterial densities (1-5 x 10(8) CFU) on the mucosa and were proinflammatory over 3 days. However, MNPE formed biofilms with significant reductions in the mucosal viability whereas neither CDC587 (hla(-)), MN8 (hla(-)), nor MNPE hlaKO formed biofilms. The latter strains were also less cytotoxic than wild-type MNPE. The addition of exogenous, purified alpha-toxin to MNPE hlaKO restored the biofilm phenotype. We speculate that alpha-toxin affects S. aureus phenotypic growth on vaginal mucosa by promoting tissue disruption and biofilm formation. Further, alpha-toxin mutants (hla(-)) are not benign colonizers, but rather form a different type of infection, which we have termed high density pathogenic variants (HDPV).
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