December 2007 - The Indian Society for Parasitology

88Singh and Jainhost immunoglobulins. Also, cysteine proteases are Lipophosphoglycan mutants have been shown to beinvolved in apoptosis of human vaginal epithelial less adherent and cytotoxic to human vaginalcells. Cysteine protease-induced programmed cell ectocervical cells, in vitro (Bastida-Corcuera et al.,death might be involved in the pathogenesis of T. 2005).vaginalis. Nearly 23 proteinases have been identifiedin T. vaginalis. Compounds which can inhibit cysteineCONCLUSIONproteinases might be active as trichomonacidal agents. Increase in both the prevalence of MTZ-resistant T.Some plant essential oils and extracts might act vaginalis strains and the number of cases of crossagainstcysteine proteinases, but more research is resistance among nitroimidazoles, indicate a need forneeded to assess their potential (Jean-Paul et al., the design, discovery and development of non-2005). Anti-retroviral protease inhibitors have also nitroimidazole drugs for the treatment of refractoryshown activity against MTZ-resistant strains of T. trichomoniasis. More research in the areas ofvaginalis (Dunn et al., 2007).pathogenesis and drug-resistance, especially atCysteine synthase: Because T. vaginalis lacksmolecular levels, is very much warranted. Specificglutathione, it relies heavily on cysteine as a majorpoints that need to be considered include: details of theredox buffer. Cysteine is synthesized from sulfidelife cycle of T. vaginalis as it would help in developingsource by the enzyme cysteine synthase. O-new strategies to control this disease, the exact role(s)phosphoserine is utilized as a substrate for cysteineplayed by immune system during T. vaginalisbiosynthesis. Levels of cysteine synthase in T.infection as nearly 50% cases remain asymptomaticvaginalis are regulated according to need. Parasitesand continues to transmit the parasite, how the parasitegrowing in an environment rich in cysteine possessestablish itself in the changing environment of vagina,low activity and vice versa. Humans lack this enzymethe exact role(s) played by phospholipids in the host-and, therefore, it could be an exploitable drug targetparasite interactions and how to utilize new targets to(Westrop et al., 2006).design potential drug candidates. There appears to be asilver lining on the horizon as a number of drugPyruvate oxidoreductases: Nitrothiazole benzamide candidates and new targets have been identified;derivative, nitazoxanide, is described as a however, still a lot needs to be done for providing anoncompetitive inhibitor of PFOR of many anaerobic safe and effective drug for the treatment and control ofparasites, including T. vaginalis. It shares structural human trichomoniasis, especially for the MTZsimilaritywith thiamine pyrophosphate, a cofactor resistant cases.involved in PFOR reaction. This agent inhibits PFORby a novel mechanism in which the anion formACKNOWLEDGEMENTSinterferes with the attachment of activated cofactor to We thank Prof. P. Rama Rao, Director, NationalPFOR, and thus, intercepts pyruvate oxidation. Thus, Institute for Pharmaceutical Education and Researchan important energy generating process gets inhibited, (NIPER), S. A. S. Nagar, for his help and continuedwithout which parasites would not be able to survive. encouragement. One of us (HJ) is grateful to NIPERBecause nitazoxanide has been proposed to target for providing financial assistance. The technical“activated cofactor” of an enzymatic reaction rather assistance rendered by Mr. Vijay Kumar Mishra, isthan any substrate or enzyme, it could be beneficial in also acknowledged.the treatment of cases where T. vaginalis acquiresmutation-based drug resistance. But, to confirm this, REFERENCESfurther studies in this area are needed (Hoffman et al.,2007).Phospholipid membrane: Lipophosphoglycan is themain surface polysaccharide in T. vaginalis. It is acomplex molecule present in high density on parasitesurface. Galactose and glucosamine are the mostp r e v a l e n t m o n o s a c c h a r i d e r e s i d u e s .Lipophosphoglycan seems to play a role in anchoringparasite to plasma membrane, resistance tocomplement, host enzymes and immune evasion.Adagu IS, Nolder D, Warhurst DC and Rossignol JS. 2002. Invitro activity of nitazoxanide and related compounds againstisolates of Giardia intestinalis, Entamoeba histolytica andTrichomonas vaginalis. J Antimicrob Chemother 49:103-111.Alderete JF, Nguyen J, Mundodi V and Lehker MW. 2004.Heme-iron increases levels of AP65-mediated adherence byTrichomonas vaginalis. Microb Pathogenesis 36:263-271.Bastida-Corcuera FD, Okumura CY, Colocoussi A and JohnsonPJ. 2005. Trichomonas vaginalis lipophosphoglycan mutantshave reduced adherence and cytotoxicity to human