Staphylococcus aureus ATP Synthase Promotes Biofilm Persistence by Influencing Innate Immunity
Megan E. Bosch, Blake P. Bertrand, Cortney E. Heim, Abdulelah A. Alqarzaee, Sujata S. Chaudhari, Amy L. Aldrich, Paul D. Fey, Vinai C. Thomas, Tammy Kielian
Abstract
Medical device-associated biofilm infections are a therapeutic challenge based on their antibiotic tolerance and ability to evade immune-mediated clearance. The virulence determinants responsible for bacterial biofilm to induce a maladaptive immune response remain largely unknown. This study identified a critical role for S. aureus ATP synthase in influencing the host immune response to biofilm infection. An S. aureus ATP synthase alpha subunit mutant (Δ atpA ) elicited heightened proinflammatory cytokine production by leukocytes in vitro and in vivo , which coincided with improved biofilm clearance in a mouse model of prosthetic joint infection. The ability of S. aureus Δ atpA to augment host proinflammatory responses was cell lysis-dependent, as inhibition of bacterial lysis by polyanethole sodium sulfanate or a Δ atpA Δ atl biofilm did not elicit heightened cytokine production. These studies reveal a critical role for AtpA in shaping the host immune response to S. aureus biofilm.