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Implementation of a Permeable Membrane Insert-based Infection System to Study the Effects of Secreted Bacterial Toxins on Mammalian Host Cells
Published on: August 19, 2016
High-frequency intracellular infection and erythrogenic toxin A expression undergo phase variation in M1 group A
P P Cleary1, L McLandsborough, L Ikeda
1Department of Microbiology, University of Minnesota, Minneapolis 55126, USA. cleary@lenti.med.umn.edu
Abstract:
A clonal variant of serotype M1 group A streptococcus, strain 90-131, disseminated to several continents, where it was associated with severe systemic infections and toxic shock. Although this strain harbours the speA gene and is efficiently internalized by human epithelial cells, clinical isolates often fail to express the erythrogenic toxin under laboratory growth conditions. Cultures of strain 90-131 were observed to phase vary between small, dry, compact and larger, more mucoid colonies. The former were shown to be poorly internalized by epithelial cells. Analysis of RNA by Northern hybridization demonstrated that the emml, hasA and speA genes were weakly transcribed in cultures derived from the small colonies and highly transcribed in those derived from the large colonies. An insertion mutation in mga (the multigene activator) downregulated the invasion of epithelial cells and the transcription of emm1 and hasA, but had little impact on the transcription of speA. These are the first data to suggest the existence of a common regulatory circuit linking intracellular invasion, M protein, hyaluronic acid capsule and erythrogenic toxin expression by group A streptococcus. Moreover, the genetic instability of toxin expression exhibited by this serotype may impact on laboratory studies that attempt to associate toxin production with toxic shock.
Insights
Group A Streptococcus strain 90-131 exhibits phase variation, affecting its ability to invade human cells and express toxins. This genetic instability impacts toxic shock research.
Area of Science:
- Microbiology
- Molecular Biology
- Infectious Diseases
Background:
- Serotype M1 group A Streptococcus strain 90-131 is linked to severe infections and toxic shock.
- Clinical isolates often show reduced erythrogenic toxin expression despite possessing the speA gene.
- Strain 90-131 exhibits colony phase variation impacting epithelial cell invasion.
Purpose of the Study:
- To investigate the regulatory mechanisms behind the variable expression of virulence factors in strain 90-131.
- To explore the link between colony morphology, epithelial cell invasion, and toxin production.
- To identify genetic factors controlling these variable traits.
Main Methods:
- Observation of colony morphology and phase variation in strain 90-131.
- Assessment of epithelial cell invasion by different colony types.
- Northern hybridization to analyze gene transcription (emm1, hasA, speA).
- Construction and analysis of an insertion mutation in the mga gene.
Main Results:
- Small, dry colonies showed poor epithelial cell invasion and weak transcription of emm1, hasA, and speA.
- Large, mucoid colonies exhibited efficient invasion and high transcription of these genes.
- A mutation in mga downregulated cell invasion and emm1/hasA transcription, with minimal effect on speA.
- These findings suggest a common regulatory circuit for invasion and virulence factors.
Conclusions:
- A common regulatory circuit likely links bacterial invasion, M protein, hyaluronic acid capsule, and erythrogenic toxin expression in group A Streptococcus.
- The genetic instability of toxin expression in this serotype may confound laboratory studies associating toxin production with toxic shock.
- Understanding these regulatory mechanisms is crucial for studying Streptococcus pyogenes virulence and pathogenesis.
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