Candida albicans Shields the Periodontal Killer Porphyromonas gingivalis from Recognition by the Host Immune System and Supports the Bacterial Infection of Gingival Tissue

Abstract

Candida albicans is a pathogenic fungus capable of switching its morphology between yeast-like cells and filamentous hyphae and can associate with bacteria to form mixed biofilms resistant to antibiotics. In these structures, the fungal milieu can play a protective function for bacteria as has recently been reported for C. albicans and a periodontal pathogen—Porphyromonas gingivalis. Our current study aimed to determine how this type of mutual microbe protection within the mixed biofilm affects the contacting host cells. To analyze C. albicans and P. gingivalis persistence and host infection, several models for host–biofilm interactions were developed, including microbial exposure to a representative monocyte cell line (THP1) and gingival fibroblasts isolated from periodontitis patients. For in vivo experiments, a mouse subcutaneous chamber model was utilized. The persistence of P. gingivalis cells was observed within mixed biofilm with C. albicans. This microbial co-existence influenced host immunity by attenuating macrophage and fibroblast responses. Cytokine and chemokine production decreased compared to pure bacterial infection. The fibroblasts isolated from patients with severe periodontitis were less susceptible to fungal colonization, indicating a modulation of the host environment by the dominating bacterial infection. The results obtained for the mouse model in which a sequential infection was initiated by the fungus showed that this host colonization induced a milder inflammation, leading to a significant reduction in mouse mortality. Moreover, high bacterial counts in animal organisms were noted on a longer time scale in the presence of C. albicans, suggesting the chronic nature of the dual-species infection.

The Role of the Oral Microbiota in the Etiopathogenesis of Oral Squamous Cell Carcinoma

“…were associated with OSCC; increased relative abundances of this fungi were observed in saliva samples from patients with OSCC compared to those taken from healthy individuals and, similarly, in tumoral tissue compared to fibroepithelial polyps [ 82 , 83 ]. A microbial coexistence of C. albicans and a periodontal pathogen P. gingivalis has been described; these two microorganisms have a relationship in which C. albicans shields the P. gingivalis from recognition by the host immune system and, in this way, supports the bacterial infection [ 118 ]. Moreover, C. albicans displays a synergistic interaction with commensal oral streptococci, which can have implications for the pathogenic potential of C. albicans in the oral mucosa [ 119 ].…”

Heme Competition Triggers an Increase in the Pathogenic Potential of Porphyromonas gingivalis in Porphyromonas gingivalis-Candida albicans Mixed Biofilm

“…The adhesion regions of Kgp and RgpA participate in the adhesion of red blood cells, while the decomposition of red blood cells and the hydrolysis of hemoglobin mainly depend on the hydrolysis regions of Kgp, RgpA, and RgpB ( Smalley et al, 2007 ; Li et al, 2011 ). In addition, the gingipains of P. gingivalis can interact with the surface proteins of C. albicans to promote the stability of the dual-species biofilm, and can also regulate the host reaction by hydrolyzing the main defense molecules ( Bartnicka et al, 2019 , 2020 ). Therefore, gingipains play an important role in the perpetuation of biofilms.…”

Candida albicans—The Virulence Factors and Clinical Manifestations of Infection

“…There is evidence of interaction between C. albicans and Porphyromonas gingivalis , a bacterium considered the most important in developing periodontitis [ 81 , 82 ]. In a biofilm model, it has been shown that, in the presence of oxygen, C. albicans creates a protective environment for P. gingivalis [ 81 , 83 ]. To conclude, Candida plays a significant role in oral infections.…”