Discussion
Trichomonas tenax is an oral anaerobic/microaerophilic flagellated protist that is reported to be associated with periodontitis and pulmonary trichomoniasis. Microbial dysbiosis, a taxonomic and functional shift in the oral microbial population towards a more pathogenic state, drives an excessive host inflammatory response and leads to periodontitis, an irreversible damage of the tissues around the teeth that is associated with aging but that can affect people of any age, including children. Periodontitis affects over 47% of adults aged ≥30 years and 5-15% of adults worldwide. It remains the leading cause of edentulism and has a major impact on the quality of life through the loss of tooth function and associated issues with eating and speaking. Difficulties with eating often lead to nutritional deficits in older people. Periodontitis is also increasingly recognised to be associated with systemic conditions including arthritis and dementia/Alzheimer.
T. tenax is positively associated with periodontitis and could contribute to the dysbiotic state associated with periodontitis through its interactions with the oral microbiota, including bacteria, Mycoplasma species, fungi and viruses. However, the precise mechanism underlying tissue damage in this pathology is still poorly understood.
We have identified a list of conserved genes of bacterial origins encoding candidate enzymes targeting bacterial peptidoglycans (PG) or fungal cell walls in the species
T. vaginalis and
T. gallinae, which are closely related to
T. tenax. This suggests that targeting of bacteria and fungi is essential for these parasites to thrive in various mucosal surfaces from different animal hosts ranging from birds to mammals including pet animals (dogs and cats) and humans. Using co-culture experiments we were able to show that
T. tenax dynamically interacts with
Candida albicans, both yeast forms, which are phagocytosed by the parasite, and hyphae forms. This is similar to published data for
T. vaginalis. Notably, targeting of bacterial and fungal cell walls can liberate pro-inflammatory molecules, hence
Trichomonas species could contribute to the damaging inflammation indirectly through the targeting of the cell walls of members the microbiota. BT_3312; an endo-1,6-β-glucanase belonging to the Glycosyl Hydrolase family 30 subfamily 3 (GH30_3) in
Bacteroides thetaiotaomicron was shown to degrade the 1,6-β-glucans of yeast cell walls. Homologues of BT_3312 were identified among
T. vaginalis and
T. gallinae annotated genes and sequence comparisons indicated that these share all the key residues from BT_3312 that mediates its specificity to fungal 1,6-β-glucans. Here we identified a GH30_3 homologue in
T. tenax (TtGH30) and investigated its phylogenetic relationship with trichomonads and bacterial homologues. As the TtGH30 sequence also possess all key residues of the BT_3312 1,6-β-glucanase we expressed it and purified a recombinant version of the enzyme and tested its activity against 1,6-β-glucans. These comparative investigations highlight a lateral gene transfer into the Trichomonas lineage from a bacterial origin that encode functional enzymes and that might contribute to target fungal cell wall
in vivo and by doing so help the parasites to thrive at mucosal surfaces, including
T. tenax in the periodontal pocket. By doing so it could also contribute at liberating the strongly pro-inflammatory fungal 1,3-β-glucans. Dual transcriptomics of
T. tenax-
C.
albicans co-culture are currently being processed to gain a more global perspective on the molecular basis of
T. tenax targeting of the fungi, including the range of enzymes potentially targeting fungal cell wall and the parasite metabolism more generally.
