Staphylococcus aureus is a Gram-positive opportunistic pathogen responsible for diverse infections, including bacteremia (SAB). Patients with rheumatoid arthritis (RA) appear to be more prone to SAB, often experiencing more severe disease and complications such as infections in bones and joints. Meanwhile, Porphyromonas gingivalis, a Gram-negative oral pathogen, has been linked to RA development, largely due to its unique peptidylarginine deiminase (PPAD) enzyme and its highly active proteases called gingipains. These virulence factors are abundant in P. gingivalis outer membrane vesicles (OMVs), small structures released from the bacterial outer membrane. Our study reveals that these OMVs trigger S. aureus to form aggregates, a process dependent on both gingipains and PPAD, which can be reversed under certain conditions. Importantly, we found that exposure to P. gingivalis OMVs enhances the uptake of S. aureus by human neutrophils without causing noticeable neutrophil death. These observations suggest a potential mechanism by which P. gingivalis may suppress competing bacteria, promoting aggregation and neutrophil-mediated internalization of S. aureus. We hypothesize that this interaction could influence host-pathogen dynamics, as neutrophils carrying internalized bacteria might facilitate bloodstream dissemination, providing a possible explanation for the increased susceptibility of RA patients to SAB.
