Staphylococcus aureus ATP Synthase Promotes Biofilm Persistence by Influencing Innate Immunity

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.