Differential Response of Oral Mucosal and Gingival Cells to Corynebacterium durum, Streptococcus sanguinis, and Porphyromonas gingivalis Multispecies Biofilms

Abstract

Polymicrobial interactions with oral mucosal surfaces determine the health status of the host. While a homeostatic balance provides protection from oral disease, a dysbiotic polymicrobial community promotes tissue destruction and chronic oral diseases. How polymicrobial communities transition from a homeostatic to a dysbiotic state is an understudied process. Thus, we were interested to investigate this ecological transition by focusing on biofilm communities containing high abundance commensal species and low abundance pathobionts to characterize the host-microbiome interactions occurring during oral health. To this end, a multispecies biofilm model was examined using the commensal species Corynebacterium durum and Streptococcus sanguinis and the pathobiont Porphyromonas gingivalis. We compared how both single and multispecies biofilms interact with different oral mucosal and gingival cell types, including the well-studied oral keratinocyte cell lines OKF4/TERT-1and hTERT TIGKs as well as human primary periodontal ligament cells. While single species biofilms of C. durum, S. sanguinis, and P. gingivalis are all characterized by unique cytokine responses for each species, multispecies biofilms elicited a response resembling S. sanguinis single species biofilms. One notable exception is the influence of P. gingivalis upon TNF-α and Gro-α production in hTERT TIGKs cells, which was not affected by the presence of other species. This study is also the first to examine the host response to C. durum. Interestingly, C. durum yielded no notable inflammatory responses from any of the tested host cells, suggesting it functions as a true commensal species. Conversely, S. sanguinis was able to induce expression and secretion of the proinflammatory cytokines IL-6 and IL-8, demonstrating a much greater inflammatory potential, despite being health associated. Our study also demonstrates the variability of host cell responses between different cell lines, highlighting the importance of developing relevant in vitro models to study oral microbiome-host interactions.

Corncob structures in dental plaque reveal microhabitat taxon specificity

“…Recent studies have found C. matruchotii and C. durum associated with health rather than caries [53][54][55]. Metabolites produced by C. durum have also been found to extend lifespan in the model organism Caenorhabditis elegans [56] and C. durum elicited no inflammatory response from human gingival and oral mucosal cells, suggesting it is a commensal [57]. S. cristatus has been shown to inhibit biofilm formation of the periodontal pathogen P. gingivalis by repression of virulence genes [58,59].…”

The effect of physical and psychological stress on the oral microbiome

“…The species Corynebacterium durum has been cultured from throat, respiratory secretions, and blood ( Bernard, 2012 ). The pathogenic potential of Corynebacterium durum remains unclear; however, recent studies on polymicrobial interactions with oral mucosal surfaces have determined C. durum functions as a commensal species ( Redanz et al, 2021 ). The genus Eikenella is a pathogen in head and neck infections and in wounds related to oral cavity contamination ( Knudsen and Simko, 1995 ).…”

Molecular commensalism: how oral corynebacteria and their extracellular membrane vesicles shape microbiome interactions

“…In other words, why are some species found only in specific locations associated with certain species, but not in others? Since beginning our work on oral corynebacteria in 2016, we have developed significant insights into both questions ( 37 , 39 – 41 ). A key finding was a unique interaction between C. durum and S. sanguinis that was not observed among various other oral streptococci: S. sanguinis , when co-cultured with C. durum , would grow into exceptionally long chains ( Figure 1B ).…”

“…Fatty acids are known for their anti-inflammatory properties ( 45 , 46 ). We previously reported that biofilms of C. durum do not trigger strong responses of IL-6 and IL-8 in oral mucosal cell lines ( 39 ). This observation, while speculative, suggests that the minimal reactive nature towards host epithelial cells, along with the decreased macrophage uptake of S. sanguinis ( 37 ), could act as a protective mechanism for oral health, perhaps via anti-inflammatory mechanisms.…”