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CcpA Coordinates Growth/Damage Balance for Streptococcus pyogenes Pathogenesis.

Elyse Paluscio1,2, Michael E Watson1,3, Michael G Caparon4

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Pathogens balance growth and damage; Streptococcus pyogenes's Carbon Catabolite Protein A (CcpA) regulates this. Mutants showed CcpA controls virulence, impacting infection and colonization differently.

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Area of Science:

  • Microbiology
  • Pathogenesis
  • Bacterial Genetics

Background:

  • Pathogens must balance replication and host damage for optimal fitness.
  • Streptococcus pyogenes utilizes Carbon Catabolite Protein A (CcpA) to regulate metabolism and virulence.
  • CcpA's role in coordinating growth and damage is crucial for S. pyogenes pathogenesis.

Purpose of the Study:

  • To investigate the role of CcpA in balancing bacterial growth and host tissue damage during infection.
  • To compare the virulence of wild-type S. pyogenes with CcpA-deficient and constitutively active CcpA mutants.
  • To elucidate how CcpA influences pathogenesis in different infection models.

Main Methods:

  • Utilized two distinct murine models: acute soft tissue infection and long-term asymptomatic mucosal colonization.
  • Generated and compared S. pyogenes mutants: one lacking CcpA and another with a constitutively DNA-binding CcpA (CcpAT307Y).
  • Assessed bacterial virulence, tissue burden, and host damage in both models.

Main Results:

  • Both CcpA mutants exhibited altered virulence compared to wild-type.
  • Loss of CcpA led to reduced growth in tissues, decreased damage, and faster bacterial clearance.
  • Constitutive CcpA activity resulted in high bacterial loads and prolonged carriage with diminished tissue damage.

Conclusions:

  • CcpA is a master regulator controlling the balance between bacterial growth and host tissue damage.
  • The activity of CcpA actively modulates pathogen fitness and virulence strategies.
  • S. pyogenes virulence network topology couples carbon metabolism with growth/damage balance, influencing pathogenesis.