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Regulation of host cell recognition in Streptococcus pyogenes
1Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
Abstract:
Protein F, a fibronectin-binding protein, and the M protein of Streptococcus pyogenes both play important roles in directing adherence to different populations of host cells in the skin. Expression of both proteins is regulated in response to alterations in atmosphere. Transcriptional control of mry, a positive-acting regulator of expression of the gene which encodes the M protein (emm) in response, to elevated levels of CO2, is a mechanism for control of emm expression in response to atmosphere. Expression of protein F is controlled at the level of transcription in response to the concentration of O2, and its expression is stimulated in the presence of superoxide. Further support for a role of superoxide in regulation of prtF expression comes from the observation that an S. pyogenes mutant which contains an insertionally inactivated gene for superoxide dismutase (sod) becomes hypersensitive to superoxide and will express prtF constitutively. A second strain also demonstrates constitutive expression of prtF but contains a functional sod. Complementation analyses in this strain using a prtF allele cloned from a regulating host and a novel method for shuttle mutagenesis which utilized the transposon mini-gamma delta have been used to identify rofA, a positive-acting regulator of prtF expression. A model for the role of the surface proteins, F and M and their regulatory genes mry and rofA in streptococcal infections of the skin will be discussed.
Insights
Streptococcus pyogenes uses Protein F and M proteins for skin adherence. Their expression is controlled by environmental factors like CO2 and O2, regulated by genes mry and rofA.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- Streptococcus pyogenes utilizes surface proteins Protein F and M for host cell adherence in skin infections.
- Expression of these proteins is influenced by atmospheric conditions.
Purpose of the Study:
- To investigate the regulatory mechanisms controlling the expression of Protein F and M in Streptococcus pyogenes.
- To identify the genes and environmental factors involved in this regulation.
Main Methods:
- Analysis of gene expression in response to varying CO2 and O2 levels.
- Study of Streptococcus pyogenes mutants with altered superoxide dismutase (sod) activity.
- Complementation analyses and shuttle mutagenesis to identify regulatory genes.
Main Results:
- M protein gene (emm) expression is transcriptionally controlled by mry in response to CO2.
- Protein F gene (prtF) expression is regulated by O2 concentration and superoxide, with constitutive expression observed in sod mutants.
- The positive regulator rofA for prtF expression was identified.
Conclusions:
- Environmental factors significantly impact Streptococcus pyogenes virulence factors.
- Specific regulatory genes (mry and rofA) control the expression of adherence proteins in response to atmospheric changes, influencing skin infections.