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Alpha-toxin promotes Staphylococcus aureus mucosal biofilm formation
Michele J Anderson1, Ying-Chi Lin, Aaron N Gillman
1Department of Experimental and Clinical Pharmacology, University of Minnesota Minneapolis, MN, USA.
Frontiers in Cellular and Infection Microbiology
|August 25, 2012
Summary
Staphylococcus aureus alpha-toxin promotes biofilm formation and vaginal tissue disruption in Toxic Shock Syndrome (TSS) USA200 strains. Alpha-toxin deficient strains exhibit reduced pathogenicity, forming distinct high-density pathogenic variants (HDPV).
Area of Science:
- Microbiology
- Infectious Diseases
- Toxicology
Background:
- Staphylococcus aureus is a significant human pathogen causing infections from skin issues to life-threatening Toxic Shock Syndrome (TSS).
- The USA200 clonal type of S. aureus is prevalent, frequently associated with TSS, and produces alpha-toxin (Hla), a key proinflammatory exotoxin.
- Understanding the role of Hla in S. aureus pathogenesis, particularly in vaginal mucosal infections, is crucial for developing targeted interventions.
Purpose of the Study:
- To investigate the differential impact of Hla production on vaginal mucosal tissue disruption by TSS S. aureus USA200 strains.
- To characterize the subsequent infection dynamics, including biofilm formation and tissue viability, in relation to Hla expression.
- To compare the pathogenicity of Hla-producing strains, Hla-deficient strains, and Hla-deficient strains complemented with exogenous Hla.
Main Methods:
- LIVE/DEAD® staining and confocal microscopy were employed to assess tissue viability and biofilm formation on vaginal mucosa.
- Infection models utilized S. aureus USA200 isolates with varying Hla production capabilities (hla(+) and hla(-)) and an isogenic hla knockout mutant.
- Exogenous purified alpha-toxin was added to Hla-deficient mutants to confirm the role of Hla in observed phenotypes.
Main Results:
- All tested TSS S. aureus USA200 strains exhibited similar bacterial densities and proinflammatory responses on vaginal mucosa over 3 days.
- Hla-producing strains (MNPE) formed biofilms and caused significant reductions in mucosal viability, unlike Hla-deficient strains (CDC587, MN8, MNPE hlaKO).
- Restoration of biofilm formation was observed in Hla-deficient mutants upon addition of exogenous alpha-toxin, confirming Hla's role.
Conclusions:
- Alpha-toxin (Hla) plays a critical role in S. aureus phenotypic growth on vaginal mucosa, promoting tissue disruption and biofilm formation.
- Hla-deficient S. aureus mutants do not act as benign colonizers but establish a distinct infection type termed high-density pathogenic variants (HDPV).
- These findings highlight Hla as a key virulence factor in TSS pathogenesis and suggest distinct infection strategies employed by S. aureus variants.
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