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.

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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