Community Development betweenPorphyromonas gingivalisandCandida albicansMediated by InlJ and Als3

Abstract

The pleiomorphic yeast Candida albicans is a significant pathogen in immunocompromised individuals. In the oral cavity, C. albicans is an inhabitant of polymicrobial communities, and interspecies interactions promote hyphal formation and biofilm formation. C. albicans colonizes the subgingival area, and the frequency of colonization increases in periodontal disease. In this study, we investigated the interactions between C. albicans and the periodontal pathogen Porphyromonas gingivalis. C. albicans and P. gingivalis were found to coadhere in both the planktonic and sessile phases. Loss of the internalin-family protein InlJ abrogated adhesion of P. gingivalis to C. albicans, and recombinant InlJ protein competitively inhibited interspecies binding. A mutant of C. albicans deficient in expression of major hyphal protein Als3 showed diminished binding to P. gingivalis, and InlJ interacted with Als3 heterologously expressed in Saccharomyces cerevisiae. Transcriptional profiling by RNA sequencing (RNA-Seq) established that 57 genes were uniquely upregulated in an InlJ-dependent manner in P. gingivalis-C. albicans communities, with overrepresentation of those corresponding to 31 gene ontology terms, including those associated with growth and division. Of potential relevance to the disease process, C. albicans induced upregulation of components of the type IX secretion apparatus. Collectively, these findings indicate that InlJ-Als3-dependent binding facilitates interdomain community development between C. albicans and P. gingivalis and that P. gingivalis has the potential for increased virulence within such communities.

Oral Candidiasis: A Disease of Opportunity

“…The described interactions between C. albicans and P. gingivalis are conflicting as, in one study, P. gingivalis was shown to induce hyphae formation producing a more invasive C. albicans phenotype, whereas other studies described P. gingivalis to exert an inhibitory effect on hyphae formation [199,200]. More recently, the C. albicans hyphal-specific adhesin Als3p was identified as the fungal receptor for the bacterial internalin family protein InlJ [201]. Furthermore, this fungal-bacterial interaction in anoxic conditions resulted in upregulation of the C. albicans secreted proteolytic enzymes Sap3 and Sap9 considered to be important virulence factors [202].…”

Biodiversity of the human oral mycobiome in health and disease

“…In addition, A. actinomycetemcomitans also binds to C. albicans hyphae and yet inhibits the fungal growth through quorum sensing signalling (Bachtiar et al, 2014). Sztukowska et al (2018) have recently characterized the interactions between C. albicans and P. gingivalis and demonstrated that coadhesion mediated by specific proteins results in major changes in gene expression by P. gingivalis, which could serve to increase their pathogenic potential. This implies that interdomain interactions can modulate oral diseases (Sztukowska et al, 2018).…”

Fungi at the Scene of the Crime: Innocent Bystanders or Accomplices in Oral Infections?

“…Other P. gingivalis-related studies however noted an antagonistic effect on the yeast-hyphal transition in C. albicans, with P. gingivalis notably downregulating hyphal related genes ALS3, HWP1, and SAP4 [38,39]. Most recently, it has been demonstrated that the attachment of P. gingivalis to C. albicans is facilitated by the virulence factor InlJ from the internalin protein family, which interacts with the C. albicans adhesin ALS3 [40]. Additionally, co-adhesion specific interactions were observed, where adhesive interactions between these pathogens appear to induce the type 9 secretion system of P. gingivalis, a system characterised as having an increased community pathogenicity [41].…”