du Teil Espina Marines, Haider Rubio Anna, Fu Yanyan, López-Álvarez Marina, Gabarrini Giorgio, van Dijl Jan Maarten
Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden.
Front Oral Health. 2022 Jul 22;3:948524. doi: 10.3389/froh.2022.948524. eCollection 2022.
is an opportunistic Gram-positive bacterial pathogen that causes a wide variety of infectious diseases, including 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, 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 outer membrane vesicles (OMVs), which are secreted nanostructures that originate from the outer membrane. Here we show that OMVs cause the aggregation of bacteria in a gingipain- and PPAD-dependent fashion, and that this aggregation phenotype is reversible. Importantly, we also show that the exposure of to OMVs of promotes the staphylococcal internalization by human neutrophils with no detectable neutrophil killing. Altogether, our observations suggest that can eliminate its potential competitor 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.
是一种机会性革兰氏阳性细菌病原体,可引起多种传染病,包括菌血症(SAB)。最近的研究表明,类风湿性关节炎(RA)是SAB的一个风险因素,因为RA患者似乎更容易患SAB,并且表现出更高程度的疾病严重程度或并发症,如骨关节炎感染。另一方面,是一种革兰氏阴性口腔细菌病原体,因其独特的瓜氨酸化酶PPAD及其高效蛋白酶(即牙龈蛋白酶)参与RA的发病机制而闻名。PPAD和牙龈蛋白酶在外膜囊泡(OMV)中含量丰富,OMV是源自外膜的分泌性纳米结构。在这里,我们表明的OMV以牙龈蛋白酶和PPAD依赖的方式导致细菌聚集,并且这种聚集表型是可逆的。重要的是,我们还表明,暴露于的OMV可促进人类中性粒细胞对葡萄球菌的内化,且未检测到中性粒细胞杀伤作用。总之,我们的观察结果表明,可以通过促进葡萄球菌聚集以及随后被中性粒细胞内化来消除其潜在竞争者。我们假设这种现象可能会对宿主产生影响,因为带有内化细菌的免疫细胞可能会促进细菌向血流的转移,这可能潜在地导致RA和SAB之间的关联。