Candida albicans Shields Porphyromonas gingivalis and Suppresses Host Immunity in Mixed-Species Periodontal Biofilms Original paper

What was studied?

This study investigated how Candida albicans alters the host’s ability to recognize and respond to Porphyromonas gingivalis, a keystone periodontal pathogen, during mixed-species biofilm formation. Using in vitro models (THP-1 macrophages and primary gingival fibroblasts) and an established mouse subcutaneous chamber model, the authors examined whether C. albicans shields P. gingivalis from immune recognition, enhances bacterial persistence, and modulates inflammatory responses. A major focus was the effect of dual-species interactions on gingipain activity, cytokine degradation, biofilm development, and the establishment of chronic infection in host tissues.

Who was studied?

THP-1 monocyte-derived macrophages and primary gingival fibroblasts obtained from healthy individuals and from patients with severe periodontitis were used to examine host cell responsiveness to fungal and bacterial factors. The in vivo portion utilized C57BL/6 mice implanted with subcutaneous titanium chambers into which P. gingivalis, C. albicans, or both organisms were introduced. Fibroblasts from periodontitis patients served as a disease-altered host reference to evaluate secondary susceptibility to fungal virulence factors. All microbial strains, host inocula, and virulence factor conditions are derived directly from the study’s controlled infection models.

Major findings and microbiome-relevant details

The study demonstrates that C. albicans significantly alters P. gingivalis pathogenicity by shielding the bacterium from host immune detection. THP-1 macrophages exposed to supernatants from mixed biofilms showed profoundly altered cytokine profiles. IL-1β increased dramatically, consistent with early inflammasome-linked responses, but IL-8 production was nearly abolished, consistent with gingipain-mediated cytokine degradation. As visualized in the ELISA data on pages 3–4, dual-species biofilms created an environment where Rgp gingipain activity rose up to ten-fold under normoxic conditions, leading to accelerated digestion of cytokines critical for neutrophil recruitment. The Western blots on page 6 confirm substantial upregulation of gingipain protein abundance in mixed biofilm conditions, supported by increased rgpA, rgpB, hagA, and kgp transcript levels.

The in vivo mouse chamber model revealed that C. albicans markedly reduces mortality associated with P. gingivalis infection, yet paradoxically enables bacterial persistence by blunting acute inflammatory responses. Survival curves and CFU data on pages 6–8 show reduced systemic dissemination of P. gingivalis when C. albicans is present, but significantly prolonged local bacterial colonization, consistent with a chronic infection phenotype. Neutrophil elastase and MPO activity remained blunted throughout co-infection (page 8), indicating impaired neutrophil activation and trafficking. This supports the concept that the fungal matrix provides physical and biochemical protection, enabling P. gingivalis to maintain high local viability without inducing strong inflammatory clearance mechanisms.

Fibroblasts from periodontitis patients exhibited markedly decreased IL-1β, IL-6, IL-8, and TNF-α production in response to purified C. albicans virulence factors (page 10), indicating long-term immune dampening resulting from chronic exposure to gingipains in vivo. This suggests that chronic periodontal environments reshape fibroblast responsiveness, likely through degradation of critical receptors such as CD14, as described in the discussion referencing gingipain-dependent receptor loss.

From a microbiome-signatures perspective, this study identifies a robust cooperative MMA pattern between C. albicans and P. gingivalis. Their co-aggregation shapes gingival ecological niches by creating low-oxygen microenvironments, altering immune responses, and promoting chronicity. This represents a prototypical cross-kingdom MMA where fungal biofilm physiology directly enhances bacterial virulence and immune evasion.

Greatest implications

The study provides compelling evidence that mixed fungal–bacterial communities fundamentally alter host–pathogen interactions. For clinicians and microbiome researchers, the findings show that P. gingivalis virulence cannot be fully understood outside the context of cross-kingdom interactions, and that C. albicans acts as a structural and immunomodulatory partner that supports chronic infection even while reducing acute mortality. This establishes a strong rationale for including fungal organisms in periodontal microbiome signatures, revising diagnostic models to account for synergistic virulence, and considering antifungals as strategies in cases of recalcitrant periodontal disease. Mechanistically, the study demonstrates that gingipain activity is not static but instead upregulated and stabilized within fungal matrices, suggesting that future microbiome targeted interventions (MBTIs) must account for the biofilm’s composite biology, and that drug repurposing interventions like fluconazole may offer a novel treatment for gingivitis.

Citation

Bartnicka D, Gonzalez-Gonzalez M, Sykut J, Koziel J, Ciaston I, Adamowicz K, Bras G, Zawrotniak M, Karkowska-Kuleta J, Satala D, Kozik A, Zyla E, Gawron K, Lazarz-Bartyzel K, Chomyszyn-Gajewska M, Rapala-Kozik M. Candida albicans Shields the Periodontal Killer Porphyromonas gingivalis from Recognition by the Host Immune System and Supports the Bacterial Infection of Gingival Tissue. Int J Mol Sci. 2020 Mar 14;21(6):1984. doi: 10.3390/ijms21061984