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A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues
Published on: February 19, 2019
Chromosomal islands of Streptococcus pyogenes and related streptococci: molecular switches for survival and virulence
Scott V Nguyen1, William M McShan2
1Department of Microbiology and Immunology, The University of Oklahoma Health Sciences Center Oklahoma City, OK, USA.
Abstract:
Streptococcus pyogenes is a significant pathogen of humans, annually causing over 700,000,000 infections and 500,000 deaths. Virulence in S. pyogenes is closely linked to mobile genetic elements like phages and chromosomal islands (CI). S. pyogenes phage-like chromosomal islands (SpyCI) confer a complex mutator phenotype on their host. SpyCI integrate into the 5' end of DNA mismatch repair (MMR) gene mutL, which also disrupts downstream operon genes lmrP, ruvA, and tag. During early logarithmic growth, SpyCI excise from the bacterial chromosome and replicate as episomes, relieving the mutator phenotype. As growth slows and the cells enter stationary phase, SpyCI reintegrate into the chromosome, again silencing the MMR operon. This system creates a unique growth-dependent and reversible mutator phenotype. Additional CI using the identical attachment site in mutL have been identified in related species, including Streptococcus dysgalactiae subsp. equisimilis, Streptococcus anginosus, Streptococcus intermedius, Streptococcus parauberis, and Streptococcus canis. These CI have small genomes, which range from 13 to 20 kB, conserved integrase and DNA replication genes, and no identifiable genes encoding capsid proteins. SpyCI may employ a helper phage for packaging and dissemination in a fashion similar to the Staphylococcus aureus pathogenicity islands (SaPI). Outside of the core replication and integration genes, SpyCI and related CI show considerable diversity with the presence of many indels that may contribute to the host cell phenotype or fitness. SpyCI are a subset of a larger family of streptococcal CI who potentially regulate the expression of other host genes. The biological and phylogenetic analysis of streptococcal chromosomal islands provides important clues as to how these chromosomal islands help S. pyogenes and other streptococcal species persist in human populations in spite of antibiotic therapy and immune challenges.
Insights
Streptococcus pyogenes chromosomal islands (SpyCI) create a reversible mutator phenotype by integrating into and excising from the host DNA mismatch repair gene mutL, impacting virulence and persistence.
Area of Science:
- Microbiology
- Genetics
- Molecular Biology
Background:
- Streptococcus pyogenes is a major human pathogen responsible for millions of infections and hundreds of thousands of deaths annually.
- Virulence in S. pyogenes is associated with mobile genetic elements, including phages and chromosomal islands (CI).
- Streptococcus pyogenes phage-like chromosomal islands (SpyCI) are linked to a mutator phenotype in the host bacteria.
Purpose of the Study:
- To investigate the mechanism and implications of the growth-dependent, reversible mutator phenotype conferred by SpyCI in S. pyogenes.
- To explore the presence and characteristics of similar chromosomal islands in related streptococcal species.
- To understand how these mobile genetic elements contribute to the persistence of streptococcal pathogens.
Main Methods:
- Analysis of SpyCI integration site within the mutL gene and its effect on downstream operon genes.
- Observation of SpyCI excision and reintegration dynamics during different growth phases (logarithmic vs. stationary).
- Comparative genomic analysis of SpyCI and related CI in other streptococcal species.
Main Results:
- SpyCI integrate into the mutL gene, disrupting DNA mismatch repair and causing a mutator phenotype during stationary phase.
- SpyCI excise during logarithmic growth, relieving the mutator phenotype and allowing episomal replication.
- Similar CI utilizing the mutL attachment site were found in other pathogenic streptococci, exhibiting conserved replication/integration genes but diverse accessory genes.
- SpyCI lack capsid genes, suggesting reliance on helper phages for dissemination.
Conclusions:
- SpyCI establish a unique, growth-dependent, and reversible mutator phenotype in S. pyogenes, potentially aiding adaptation and persistence.
- The presence of similar CI across related streptococcal species highlights a conserved strategy for virulence and host adaptation.
- Understanding these mobile genetic elements offers insights into streptococcal pathogenesis and survival against therapeutic and immune pressures.
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