The role of SaeR/S in secondary Staphylococcus aureus Pneumonia

Abstract

Methicillin?resistant Staphylococcus aureus (MRSA) is a Gram?positive pathogen capable of causing diverse disease in humans. MRSA precisely controls virulence factor expression via the SaeR/S two?component gene regulatory system. While much is known about SaeR/S regulation patterns during skin infection, less is understood about the role it plays in the pulmonary environment during secondary staphylococcal pneumonia. Using an isogenic deletion mutant in pulsed field gel electrophoresis type USA300 (strain LAC) of the saeR/S two?component gene regulatory system we examined its role in mouse models of pathogenesis involving primary infection with influenza strain A/WSN/33 followed by USA300 infection. Results demonstrate SaeR/S contributes significantly to mortality during pneumonia following influenza A infection. Reverse transcription PCR and QuantiGene 2.0 assays revealed differences in both transcription of components of SaeR/S as well as virulence factors under SaeR/S control. Primary Influenza infection was seen to up regulate expression of virulence factors under control due to antecedent influenza A infection. These data underscore the importance of pathogen contribution to the pathogenesis of secondary pneumonia.