Trichomonad invasion of the mucous layer requires adhesins, mucinases, and motility

Abstract

Background/objective: Trichomonas vaginalis, the causal agent of trichomonosis, is a flagellated parasitic protozoan that colonises the epithelial cells of the human urogenital tract. The ability of T vaginalis to colonise this site is in part a function of its ability to circumvent a series of non-specific host defences including the mucous layer covering epithelial cells at the site of infection. Mucin, the framework molecule of mucus, forms a lattice structure that serves as a formidable physical barrier to microbial invasion. The mechanism by which trichomonads traverse the mucous covering is unknown. Proteolytic degradation of mucin, however, may provide for a mechanism to penetrate this layer. The goal, therefore, was to determine how trichomonads cross through a mucous layer. Methods: Secreted trichomonad proteinases were analysed for mucinase activity by mucin substrate-sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The importance of trichomonad mucinases for traversing the mucous layer was examined on an artificial mucin layer in invasion chambers. Adherence to mucin and tissue culture cells was measured using a microtitre plate assay. Results: Trichomonad isolate 24402 secreted five proteinases when incubated in PBS. All five proteinases were shown to possess mucinase activity. These mucinases were able to degrade bovine submaxillary mucin and to a lesser extent porcine stomach mucin. These enzymes were active over a pH range of 4.5-7.0 and were inhibited with cysteine proteinase inhibitors. Furthermore, T vaginalis was shown to bind to mucin possibly via a lectin-like adhesin. Adherence to mucin was increased threefold when parasites were grown in iron deficient medium. Adherence to soluble mucin prevented attachment to HeLa cells. Proteinase activity, adherence, and motility were required for trichomonads to traverse a mucin layer in vitro. Conclusions: These results show that trichomonads can traverse the mucous barrier first by binding mucin followed by its proteolytic degradation. The data further underscore the importance of trichomonad proteinases in the pathogenesis of trichomonosis. Finally, this study suggests that interference with trichomonad mucin receptors and proteinases may be a strategy to prevent colonisation by this parasite. (Sex Transm Inf 1999;75:231-238)

Mucins in the host defence against Naegleria fowleri and mucinolytic activity as a possible means of evasion

“…This is the first host innate immune response that attempts to eliminate the foreign agent. It has been reported that other protozoan parasites that infect their host by invading mucosal tissues produce lytic enzymes that degrade mucus glycoproteins (Lehker & Sweeney, 1999;Moncada et al, 2003aMoncada et al, , 2005. This degradation of mucins is essential for parasite evasion of the host response and to gain final access to target tissues.…”

Interaction of Trichomonas vaginalis and Tritrichomonas foetus with keratin: an important role in parasite infection

“…Trichomonads have proteolytic enzymes called mucinases that digest the mucus and allow the parasites to access to VECs (Alderete & Garza 1988, Lehker & Sweeney 1999. The description of a strawberry cervix in Trichomonas-positive patients (Wølner-Hanssen et al 1989, Kassem & Majoud 2006 led us to hypothesise that trichomonads could interact with keratin, either to gain access to deeper parts of the vaginal epithelium or to use this protein as nutrition.…”

“…The large variety of structures involved in parasite adhesion, including proteins (Lehker & Sweeney 1999, Mundodi et al 2004, sugars (Mirhaghani & Warton 1998) and lipophosphoglycans (Bastida-Corcuera et al 2005), indicates that trichomonads have the ability to adapt to various types of surfaces to establish infection. The ability of trichomonads to interact with keratin and ingest keratin particles could be very important for three reasons.…”

“…Trichomonads can interact and cross the mucus barrier on vaginal epithelia (Alderete & Garza 1988, Lehker & Sweeney 1999 and this might link to the clinical manifestation known as colpitis macularis or strawberry cervix (Wølner-Hanssen et al 1989, Kassem & Majoud 2006. However, the urogenital tract also displays some keratinised areas and the interaction between trichomonads and keratin has not been studied yet.…”

Mechanisms ofTritrichomonas foetusPathogenicity in Cats with Insights from Venereal Trichomonosis

“…The epithelium of the vagina is rich in mucin glycoproteins and antimicrobial factors (such as immunoglobulin and lactoferrin) that serve as barriers against pathogen invasion. In vitro studies indicate that T. vaginalis can adhere to and penetrate bovine submaxillary and porcine stomach mucus 42. In vivo, mucinase activity may allow trichomonads to solubilize the mucus matrix and gain access to the underlying vaginal epithelium (Fig 1B).…”