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Humanized Mouse Model to Study Bacterial Infections Targeting the Microvasculature
Published on: April 1, 2014
The Group A Streptococcus serotype M2 pilus plays a role in host cell adhesion and immune evasion
Jia-Yun C Tsai1,2, Jacelyn M S Loh1,2, Fiona Clow1
1Department of Molecular Medicine & Pathology, School of Medical Sciences.
Abstract:
Group A Streptococcus (GAS), or Streptococcus pyogenes, is a human pathogen that causes diseases ranging from skin and soft tissue infections to severe invasive diseases, such as toxic shock syndrome. Each GAS strain carries a particular pilus type encoded in the variable fibronectin-binding, collagen-binding, T antigen (FCT) genomic region. Here, we describe the functional analysis of the serotype M2 pilus encoded in the FCT-6 region. We found that, in contrast to other investigated GAS pili, the ancillary pilin 1 lacks adhesive properties. Instead, the backbone pilin is important for host cell adhesion and binds several host factors, including fibronectin and fibrinogen. Using a panel of recombinant pilus proteins, GAS gene deletion mutants and Lactococcus lactis gain-of-function mutants we show that, unlike other GAS pili, the FCT-6 pilus also contributes to immune evasion. This was demonstrated by a delay in blood clotting, increased intracellular survival of the bacteria in macrophages, higher bacterial survival rates in human whole blood and greater virulence in a Galleria mellonella infection model in the presence of fully assembled FCT-6 pili.
Insights
Group A Streptococcus M2 pili, distinct from others, aid bacterial adhesion and immune evasion. This unique FCT-6 pilus enhances survival in host environments and infection models.
Area of Science:
- Microbiology
- Immunology
- Molecular Biology
Background:
- Group A Streptococcus (GAS) causes diverse infections, with pilus types encoded in the FCT region influencing virulence.
- Specific GAS strains possess unique pilus structures crucial for their pathogenic mechanisms.
Purpose of the Study:
- To functionally analyze the serotype M2 pilus encoded by the FCT-6 genomic region in GAS.
- To investigate the adhesive properties and role in immune evasion of the FCT-6 pilus.
Main Methods:
- Functional analysis of pilin components, including ancillary pilin 1 and backbone pilin.
- Utilized recombinant pilus proteins, GAS gene deletion mutants, and Lactococcus lactis gain-of-function mutants.
- Assessed bacterial interactions with host cells, blood clotting, intracellular survival in macrophages, and survival in human whole blood.
Main Results:
- The ancillary pilin 1 of the FCT-6 pilus lacks adhesive properties.
- The backbone pilin mediates host cell adhesion and binds fibronectin and fibrinogen.
- The FCT-6 pilus contributes to immune evasion, evidenced by delayed blood clotting and enhanced bacterial survival in host immune environments.
- Fully assembled FCT-6 pili increased virulence in a Galleria mellonella infection model.
Conclusions:
- The FCT-6 pilus of GAS serotype M2 exhibits unique characteristics, differing from other GAS pili in its functional roles.
- This pilus is crucial for both host cell adhesion and significant immune evasion mechanisms.
- The FCT-6 pilus represents a novel target for understanding and potentially combating GAS pathogenesis.
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