Porphyromonas gingivalis-Helicobacter pylori co-incubation enhances Porphyromonas gingivalis virulence and increases migration of infected human oral keratinocytes

Abstract

Background Porphyromonas gingivalis is part of the subgingival biofilm and a keystone species in the development of periodontitis. Interactions between P.gingivalis and other bacteria in biofilms have been shown to affect bacterial virulence. Helicobacter pylori also inhabits the subgingival biofilm, but the consequences of interactions there with P.gingivalis remain unknown. Here, we investigated how the pre-incubation of P.gingivalis with H.pylori affects P.gingivalis virulence. Methods We assayed P.gingivalis internalization by oral keratinocytes (OKs), hemagglutination and biofilm formation to identify alterations in virulence after pre-incubation with H. pylori . Also, we evaluated viability and migration of OKs infected with P. gingivalis, as well as the role of toll-like receptor 4 (TLR4). In addition, we quantified the mRNA of genes associated with P.gingivalis virulence. Results Pre-incubation of P.gingivalis with H.pylori enhanced P.gingivalis biofilm formation, bacterial internalization into OKs and hemagglutination. Infection with pre-incubated P.gingivalis increased OK migration in a manner dependent on the O-antigen and linked to increased expression of the gingipain RgpB. Also, OK TLR4 participates in these events, because upon TLR4 knock-down, pre-incubated P.gingivalis no longer stimulated OK migration. Discussion We provide here for the first time insight to the consequences of direct interaction between P.gingivalis and H.pylori. In doing so, we shed light on the mechanism by which H. pylori presence in the oral cavity increases the severity or progression of periodontitis.

Host insulin resistance caused by Porphyromonas gingivalis-review of recent progresses

“…Escape of neutrophils and killing by destructive macrophages paves the way for the long-term persistence of Pseudomonas gingivalis . Then down-regulates the differentiation and development of adaptive immune cells: The ability to manipulate T-cell differentiation and immune responses provides for the survival of Pseudomonas gingivalis in the host ( Soto et al., 2022 ). Low-grade inflammation induced by the innate immune system occurs under the control of the adaptive immune system, and if the immune system is compromised, the presence of bacteria at the site of infection may lead to systemic inflammation, thereby exacerbating insulin resistance ( Harding et al., 2017 ; Ganz et al., 2022 ).…”

Helicobacter pylori in the Oral Cavity: Current Evidence and Potential Survival Strategies

“…The total proportion of periodontal pathogens in oral H. pylori -positive subgingival plaque samples was higher than that in H. pylori -negative samples [ 40 ], indicating that oral H. pylori infection may promote periodontal disease by altering the microecology. Preincubation of Porphyromonas gingivalis ( P. gingivalis ) with H. pylori affects P. gingivalis virulence, including biofilm formation, bacterial internalization into oral keratinocytes, and hemagglutination, indicating that the direct interaction between P. gingivalis and H. pylori in subgingival plaque may increase the severity or progression of periodontitis [ 41 ]. In addition, the expression of periodontitis-related protein Wnt5a and cytokines IL-8, IL-6, and INF-γ was significantly increased after cagA + H. pylori stimulated the human leukemia mononuclear cell line, suggesting that H. pylori can aggravate inflammation progression [ 40 ].…”

“…H. pylori may promote the severity of periodontitis. Preincubation of P. gingivalis with H. pylori enhanced P. gingivalis virulence, including biofilm formation, bacterial internalization into oral keratinocytes, and hemagglutination [ 41 ]. In addition, the role of F. nucleatum in the survival of H. pylori is worthy of further investigation, as H. pylori -negative chronic gastritis patients were reported to have lower levels of F. nucleatum in saliva than healthy subjects [ 124 ].…”

Co-Culture of P. gingivalis and F. nucleatum Synergistically Elevates IL-6 Expression via TLR4 Signaling in Oral Keratinocytes

“…Furthermore, research in our laboratory has shown that P. gingivalis can also interact with Helicobacter pylori, also present in the oral bacterial community. This interaction results in increases in the virulence of P. gingivalis and the expression of RgpB gingipain and is directly associated with the enhanced migration of infected cells [16].…”

“…Co-culture models are vital for studying interactions between prokaryotic and oral eukaryotic cells, unraveling the pathogenesis of polymicrobial diseases, such as oral conditions [24]. These models enable researchers to explore co-culture dynamics, revealing effects on bacterial gene expression and virulence [15,16,19,25]. In a previous study, it was demonstrated that LPS purified from P. gingivalis co-cultured with F. nucleatum increased the expressions and secretions of IL-1β, IL-6, and IL-8 in monocytes when compared to the effect of purified LPS derived from monocultured P. gingivalis [25].…”