Lethality of Staphylococcus aureus in murine pneumonia is due to alpha-toxin and other secreted factors regulated by agr and sar.

摘要

The purpose of these studies was to determine if the S. aureus global regulators agr and sar play a role in staphylococcal pneumonia and if the virulence factors regulated by them contributed to the severity of staphylococcal pneumonia. To determine this, we established a pneumonia model in mice in order to identify if S. aureus global regulators agr and sar play a role in the pathogenesis of staphylococcal pneumonia. As well, we took steps to identify the extracellular factors responsible for the lethality in a murine model of staphylococcal pneumonia and determine if these factors involved in disease process could be used as targets for immune therapy.;My work revealed that lethal pneumonia in a mouse model is dependent on the S. aureus global regulators agr and sar. This study also revealed that the lethality associated with our model is due to secreted factors, regulated by S. aureus global regulators agr and sar. Further investigation demonstrated that alpha-toxin is a major virulence factor involved in the lethality in our model. By generating an alpha-toxin deficient strain in S. aureus RN6390, we show a reduced virulence in our disease model. As well, antiserum to alpha-toxin, when administered with a lethal dose of S. aureus RN6390 protected animals from death. By evaluating the role of alpha-toxin's ability to contribute to lethality, we assessed numerous strains of S. aureus in our pneumonia model. We discovered that there was a correlation to alpha-toxin production levels and lethality in our pneumonia model. However, our study also demonstrated that alphatoxin is not the only factor involved in the disease process.