Adhesion requirements of methicillin-resistant Staphylococcus aureus in bacterial pneumonia and influenza super-infection

Abstract

Abstract In the respiratory tract, Staphylococcus aureus is associated with infections ranging from asymptomatic colonization to severe necrotizing pneumonia. While staphylococcal pneumonia has always been highly associated with influenza infections in young children and the elderly, it has emerged as the major cause of pneumonia associated with influenza since the 2009 H1N1 pandemic. Despite the clinical relevance of methicillin-resistant S. aureus (MRSA), few studies have examined bacterial factors of MRSA in pneumonia and how preceding influenza may alter the behavior of MRSA in the lung. Successful establishment of infection by bacterial pathogens requires adhesion to host cells. Staphylococcal species express a broad range of surface proteins that are involved in adhesion to host cells, known as the MSCRAMM family. MSCRAMM proteins have known roles in upper respiratory tract colonization, however their role in the lung is unknown. Preliminary data suggest that the MSCRAMM family members are important within the lung as MRSA lacking all MSCRAMMs (ΔsrtA) has decreased immune infiltrate in influenza super-infection. Additionally, the MSCRAMM family member SdrD has a role in both bacterial adherence as well as epithelial integrity and immunity in MRSA pneumonia and super-infection. Mice infected with MRSA lacking SdrD (ΔsdrD) have lower bacterial burden and increased expression of epithelial antimicrobial peptides cathelicidin and Reg3g with no difference in overall inflammation measured by immune infiltrate and pro-inflammatory cytokine levels. This suggests that MSCRAMM family members play a role in infection within the lung in both MRSA pneumonia and super-infection and can alter the immune response.