Streptococcus agalactiae

Streptococcus agalactiae (or Group B Streptococcus, GBS), asymptomatically colonizes the gastrointestinal and genitourinary tracts of 10-30% of healthy women. The bacterium can, however, cause serious infections in pregnant women and is the main case of fatal invasive disease in newborns. To cause meningitis, GBS spreads in the bloodstream causing sepsis, and finally disrupts the blood-brain barrier gaining entry into the central nervous system. GBS is also recognized as an ever-growing cause of severe invasive infections (bacteremia and sepsis) in elderly and immunocompromised patients. In both newborns and adults, GBS must overcome host innate immune mechanisms to survive in the bloodstream. Key components of innate immunity are antimicrobial peptides and proteins that vary from 10 to 150 amino acids. The major antibacterial factor in human acute phase serum against many Gram-positive bacteria is human group IIA secreted phospholipase A(hGIIA), a 14 kDa cationic enzyme. Resistance to hGIIA is crucial for GBS to establish bloodstream infections. 

The goal of this project is to identify the genetic factors conferring resistance/susceptibility to hGIIA in GBS using two approaches: 1) direct mutagenesis of the genes involved in cell wall biosynthesis followed by hGIIA susceptibility analysis of the mutants and 2) screening GBS transposon mutant libraries against lethal and sub-lethal concentrations of hGIIA.