Neutralizing the GBS hemolytic lipid toxin

PROJECT SUMMARY Human morbidity and mortality due to bacterial infections continue to remain significant public health concern. Group B Streptococcus (GBS) or Streptococcus agalactiae cause invasive infections during pregnancy leading to preterm births, stillbirths or infections in newborns. Furthermore, GBS also cause infections in the normal, elderly, diabetic and immuno-compromised adults. Our work has shown that the hemolysin, which is a key virulence factor for GBS infections is a pigmented ornithine rhamnolipid also known as granadaene. This hemolytic lipid toxin is cytotoxic to a number of host cells leading to adverse outcomes to newborns and adult humans. The objectives of this proposal are to identify additional nontoxic analogs that can prevent toxin function during GBS infections using murine models of infection, to elucidate host immune mechanisms important for analog mediated immunity against this GBS toxin, to determine how membrane vesicles exacerbate GBS pathogenesis and if antibodies can attenuate their effects. Collectively, the results from these aims will be important and relevant for prevention of GBS infections in humans and will be relevant to other diseases caused by pathogens encoding toxic lipids.