Outer membrane vesicles of the oral pathogen Porphyromonas gingivalis promote aggregation and phagocytosis of Staphylococcus aureus

Abstract

<i>Staphylococcus aureus</i> is an opportunistic Gram-positive bacterial pathogen that causes a wide variety of infectious diseases, including <i>S. aureus</i> bacteremia (SAB). Recent studies showed that rheumatoid arthritis (RA) is a risk factor for SAB, as RA patients appear to be more susceptible to SAB and display higher degrees of disease severity or complications, such as osteoarticular infections. On the other hand, <i>Porphyromonas gingivalis</i> is a Gram-negative bacterial oral pathogen, which is notable for its implication in the etiopathogenesis of RA due to its unique citrullinating enzyme PPAD and its highly effective proteases, known as gingipains. Both PPAD and gingipains are abundant in <i>P. gingivalis</i> outer membrane vesicles (OMVs), which are secreted nanostructures that originate from the outer membrane. Here we show that <i>P. gingivalis</i> OMVs cause the aggregation of <i>S. aureus</i> bacteria in a gingipain- and PPAD-dependent fashion, and that this aggregation phenotype is reversible. Importantly, we also show that the exposure of <i>S. aureus</i> to OMVs of <i>P. gingivalis</i> promotes the staphylococcal internalization by human neutrophils with no detectable neutrophil killing. Altogether, our observations suggest that <i>P. gingivalis</i> can eliminate its potential competitor <i>S. aureus</i> by promoting staphylococcal aggregation and the subsequent internalization by neutrophils. We hypothesize that this phenomenon may have repercussions for the host, since immune cells with internalized bacteria may facilitate bacterial translocation to the blood stream, which could potentially contribute to the association between RA and SAB.