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Emergence of a bacterial clone with enhanced virulence by acquisition of a phage encoding a secreted phospholipase A2

Izabela Sitkiewicz1, Michal J Nagiec, Paul Sumby

  • 1Center for Molecular and Translational Human Infectious Diseases Research, Methodist Hospital Research Institute, Houston, TX 77030, USA.

Proceedings of the National Academy of Sciences of the United States of America
|October 18, 2006
PubMed

Insights

The acquisition of a specific bacteriophage significantly enhanced the virulence and spread of a Group A Streptococcus clone. This study identifies a key molecular event driving severe bacterial infections.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Infectious Diseases

Background:

  • The molecular mechanisms behind the emergence of new pathogen clones are not well understood.
  • A hypervirulent clone of serotype M3 Group A Streptococcus (GAS) emerged in the mid-1980s, potentially due to bacteriophage acquisition.
  • A secreted phospholipase A2 (SlaA) encoded by this bacteriophage is suspected to be a virulence factor, but this lacks experimental validation.

Purpose of the Study:

  • To experimentally investigate the role of SlaA in the virulence and pathogenesis of serotype M3 Group A Streptococcus.
  • To determine if SlaA contributes to bacterial adherence, host cell killing, and disease progression in animal models.

Main Methods:

  • Construction and characterization of an isogenic DeltaslaA mutant strain of serotype M3 GAS.
  • In vitro assays assessing bacterial adherence to and killing of human epithelial cells.
  • In vivo studies evaluating bacterial virulence in mouse models and colonization in a non-human primate model of pharyngitis.
  • Assessment of protective immunity through immunization with purified SlaA in mice.

Main Results:

  • The DeltaslaA mutant strain showed significantly reduced adherence to and killing of human epithelial cells compared to the wild-type strain.
  • The mutant strain exhibited decreased virulence in a mouse model and was attenuated in colonizing the pharynx in a monkey model.
  • Immunization with SlaA provided significant protection against invasive disease in mice.

Conclusions:

  • Transductional acquisition of the SlaA gene enhanced the spread and virulence of the serotype M3 GAS precursor strain.
  • SlaA is a crucial virulence factor contributing to the evolution and dissemination of this hypervirulent bacterial clone.
  • These findings elucidate a key molecular event responsible for the emergence of severe human infections caused by this specific GAS clone.

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