The binding of Tritrichomonas foetus to immobilized laminin-1 and its role in the cytotoxicity exerted by the parasite

Abstract

The recognition and binding of pathogens to extracellular matrix glycoproteins may determine the outcome of infective processes. The interaction between the bovine urogenital parasite Tritrichomonas foetus and the major basal membrane glycoprotein laminin-1 (LMN-1) was investigated. The chemical nature of parasite molecules involved in the attachment of T. foetus to immobilized LMN-1 and the influence of LMN-1 in the toxicity exerted by the parasite to HeLa cells was studied. Attachment of T. foetus to LMN-1 resulted in notable morphological alterations of the parasite, which became amoeboid. T. foetus recognized LMN-1 through specific amino acid sequences (AG73, C16, A208 and A13) in the LMN-1 molecule, and the protein nature of the parasite molecules involved in the recognition was demonstrated by dot-blot analyses. Such molecular recognition was cation-dependent and five LMN-1-binding molecules (220, 200, 130, 125 and 80 kDa) were identified in T. foetus. Binding of T. foetus to LMN-1 rendered the parasite toxic to HeLa cell monolayers. Thus, LMN-1 appears to provide signalling cues that mediate important cell functions in T. foetus concerning its interaction with host cells. INTRODUCTIONTritrichomonas foetus is a venereal pathogen of naturally bred cattle which may cause infertility and abortion (BonDurant, 2005). The related pathology, usually referred to as bovine trichomoniasis, includes different clinical manifestations between bulls and cows (BonDurant, 1997). In bulls the parasite can be detected at the preputial cavity to the urethra, and also in deeper parts of the urogenital tract (Parsonson et al., 1974). Once infected, bulls may harbour T. foetus throughout their lives without exhibiting clinical symptoms. In contrast, among cows the effects of the disease range from asymptomatic to severe clinical manifestations including vaginitis, cervicitis, endometritis and pyometra, resulting in transient infertility or fetal loss. Such clinical characteristics indicate the ability of T. foetus to invade host tissues (Parsonson et al., 1976;Ló pez et al., 2000). Trichomonads possess a diversity of surface glycoconjugates including adhesins (Corbeil et al., 1989;Singh et al., 1999;Alderete & Garza, 1988) and extracellular matrix (ECM)-binding molecules (Silva-Filho et al., 1988), which play important roles during the interaction of the parasites with their hosts.In mammals, the ECM is composed of a complex assortment of glycoproteins and proteoglycans, which not only serve as scaffolds to provide a structural framework for tissues but also regulate cell behaviour (Bissell & Barcellos-Hoff, 1987;Nelson & Bissel, 2006). Among the ECM components, laminin-1 (LMN-1) is a large (#850 kDa) glycoprotein involved in various biological phenomena (Ekblom et al., 2003). LMN-1 provides signalling cues mediating important cell functions, including cell adhesion (Arrighi & Hurd, 2002;Ghosh et al., 1999;Gordon et al., 1993;Silva-Filho et al., 2002) and invasiveness by micro-organisms (Bandyopadhyay et al., 2001;Li et al., ...

Acanthamoeba Interaction with Extracellular Matrix Glycoproteins: Biological and Biochemical Characterization and Role in Cytotoxicity and Invasiveness

“…Both laminin proteins yielded a comparable pattern of protein binding, which is consistent with the similarity between mouse and human laminins (Nissinen et al 1991). Laminin‐binding proteins have been described in pathogenic microorganisms, including bacteria (Ferreira et al 2006; Ljungh, Moran, and Wadstrom 1996), fungi (Gonzalez et al 2005), and protozoa (Ghosh et al 1996; Giordano et al 1994; Li et al 1995; Petropolis et al 2008; Silva‐Filho et al 1988), suggesting that LM recognition may be a critical step for progression of invasive infection. Laminin‐binding proteins in Acanthamoeba also have been reported (Hong et al 2004; Kong et al 2001).…”

The commensal protistTritrichomonas musculusexhibits a dynamic life cycle that induces extensive remodeling of the gut microbiota

“…This may suggest a change in host adhesive properties or antigenicity as the protist adopts different cell states during its life cycle. Related trichomonads T. vaginalis and T. foetus are known to exist in one of three forms-actively growing trophozoites, host-adherent amoeboid cells or environmentally resistant pseudocysts 41,42,[65][66][67] . The capture of actively metabolizing T. mu undergoing cell cycle in the scRNA-Seq data, and cells with stress-activated pathways neighbouring those expressing relatively fewer genes (with little to no expression of adhesins) suggests we have captured at least the trophozoite and pseudocyst states.…”

Comparative aspects of immunity and vaccination in human and bovine trichomoniasis: a review

“…Cyto-adherence and cytotoxicity (Petrópolis et al 2008;Ramon-Luing Lde et al 2011) are thought to be the principal mechanism. Binding of trichomonads to vaginal epithelial cells for colonization and infection is dependent on adhesion molecules on the surface of the parasites, either alone or with other soluble parasite molecules such as hydrolytic enzymes (Peterson and Alderete 1982;Neale and Alderete 1990;Lockwood et al 1984;Hernandez et al 2011), cytotoxic molecules (Ramon-Luing Lde et al 2011;Lucas et al 2008), cell detaching (Garber et al 1989), or cell lytic factors (Alvarez-Sanchez et al 2000;Kennett et al 2002).…”