Current and future perspectives on the chemotherapy of the parasitic protozoa Trichomonas vaginalis and Entamoeba histolytica

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

Bibliography

• 1  Cosar C, Julou L. Activite de l’(hydroxy-2´ethyl)-1 methyl-2 nitro-5 imidazole (8.823 R. P.) vis-a-vis des infections experimentales a Trichomonas vaginalis. Ann. Inst. Pasteur. (Paris)96(2),238–241 (1959).Medline, CAS, Google Scholar
• 2  Lopez Nigro MM, Palermo AM, Mudry MD, Carballo MA. Cytogenetic evaluation of two nitroimidazole derivatives. Toxicol. In Vitro17(1),35–40 (2003).Crossref, Medline, CAS, Google Scholar
• 3  Celik A, Aras Ates N. The frequency of sister chromatid exchanges in cultured human peripheral blood lymphocyte treated with metronidazole in vitro. Drug. Chem. Toxicol.29(1),85–94 (2006).Crossref, Medline, CAS, Google Scholar
• 4  Crozet MD, Botta C, Gasquet M et al. Lowering of 5-nitroimidazole’s mutagenicity: towards optimal antiparasitic pharmacophore. Eur. J. Med. Chem.44,653–659 (2009).Crossref, Medline, CAS, Google Scholar
• 5  Kissinger P, Secor WE, Leichliter JS et al. Early repeated infections with Trichomonas vaginalis among HIV-positive and HIV-negative women. Clin. Infect. Dis.46(7),994–999 (2008).Crossref, Medline, Google Scholar
• 6  Dunn LA, Andrews KT, McCarthy JS et al. The activity of protease inhibitors against Giardia duodenalis and metronidazole-resistant Trichomonas vaginalis. Int. J. Antimicrob. Agents.29(1),98–102 (2007).Crossref, Medline, CAS, Google Scholar
• 7  Schwebke JR, Barrientes FJ. Prevalence of Trichomonas vaginalis isolates with resistance to metronidazole and tinidazole. Antimicrob. Agents Chemother.50(12),4209–4210 (2006).Crossref, Medline, CAS, Google Scholar
• 8  Schwebke JR, Burgess D. Trichomoniasis. Clin. Microbiol. Rev.17(4),794–803 (2004).Crossref, Medline, Google Scholar
• 9  Bogitsh BJ, Carter CE, Oeltmann TN. Human Parasitology. Elsevier, Burlington, MA, USA (2005).Google Scholar
• 10  Pereira-Neves A, Ribeiro KC, Benchimol M. Pseudocysts in trichomonads – new insights. Protist.154(3–4),313–329 (2003).Crossref, Medline, Google Scholar
• 11  Nelson KE, Masters Williams CF. Infectious Disease Epidemiology: Theory and Practice. Jones and Bartlett, Sudbury, MA, USA (2007).Google Scholar
• 12  Cotch MF, Pastorek JG 2nd, Nugent RP et al.Trichomonas vaginalis associated with low birth weight and preterm delivery. The Vaginal Infections and Prematurity Study Group. Sex. Transm. Dis.24(6),353–360 (1997).Crossref, Medline, CAS, Google Scholar
• 13  Pastorek JG 2nd, Cotch MF, Martin DH, Eschenbach DA. Clinical and microbiological correlates of vaginal trichomoniasis during pregnancy. The Vaginal Infections and Prematurity Study Group. Clin. Infect. Dis.23(5),1075–1080 (1996).Crossref, Medline, Google Scholar
• 14  Van Der Pol B, Williams JA, Orr DP, Batteiger BE, Fortenberry JD. Prevalence, incidence, natural history, and response to treatment of Trichomonas vaginalis infection among adolescent women. J. Infect. Dis.192(12),2039–2044 (2005).Crossref, Medline, CAS, Google Scholar
• 15  Wendel KA, Workowski KA. Trichomoniasis: challenges to appropriate management. Clin. Infect. Dis.44(Suppl. 3),S123–S129 (2007).Crossref, Medline, Google Scholar
• 16  Xu JJ, Wang N, Lu L et al. HIV and STIs in clients and female sex workers in mining regions of Gejiu City, China. Sex. Transm. Dis.35(6),558–565 (2008).Crossref, Medline, Google Scholar
• 17  Moodley P, Wilkinson D, Connolly C, Moodley J, Sturm AW. Trichomonas vaginalis is associated with pelvic inflammatory disease in women infected with human immunodeficiency virus. Clin. Infect. Dis.34(4),519–522 (2002).Crossref, Medline, Google Scholar
• 18  Krieger JN, Jenny C, Verdon M et al. Clinical manifestations of trichomoniasis in men. Ann. Intern. Med.118(11),844–849 (1993).Crossref, Medline, CAS, Google Scholar
• 19  Borchardt KA, al-Haraci S, Maida N. Prevalence of Trichomonas vaginalis in a male sexually transmitted disease clinic population by interview, wet mount microscopy, and the InPouch TV test. Genitourin Med71(6),405–406 (1995).Medline, CAS, Google Scholar
• 20  Helms DJ, Mosure DJ, Metcalf CA et al. Risk factors for prevalent and incident Trichomonas vaginalis among women attending three sexually transmitted disease clinics. Sex. Transm. Dis.35(5),484–488 (2008).Crossref, Medline, Google Scholar
• 21  Miller M, Liao Y, Gomez AM, Gaydos CA, D’Mellow D. Factors associated with the prevalence and incidence of Trichomonas vaginalis infection among African American women in New York city who use drugs. J. Infect. Dis.197(4),503–509 (2008).Crossref, Medline, Google Scholar
• 22  McClelland RS, Sangare L, Hassan WM et al. Infection with Trichomonas vaginalis increases the risk of HIV-1 acquisition. J. Infect. Dis.195(5),698–702 (2007).Crossref, Medline, Google Scholar
• 23  Van Der Pol B, Kwok C, Pierre-Louis B et al.Trichomonas vaginalis infection and human immunodeficiency virus acquisition in African women. J. Infect. Dis.197(4),548–554 (2008).Crossref, Medline, Google Scholar
• 24  Price MA, Stewart SR, Miller WC et al. The cost–effectiveness of treating male trichomoniasis to avert HIV transmission in men seeking sexually transmitted disease care in Malawi. J. Acquir. Immune Defic. Syndr.43(2),202–209 (2006).Crossref, Medline, Google Scholar
• 25  Sena AC, Miller WC, Hobbs MM et al.Trichomonas vaginalis infection in male sexual partners: implications for diagnosis, treatment, and prevention. Clin. Infect. Dis.44(1),13–22 (2007).Crossref, Medline, Google Scholar
• 26  National Institute of Health News. Scientists Sequence Genome of Parasite Responsible for Common Sexually Transmitted Infection. National Institues of Health, USA (2007).Google Scholar
• 27  US CDC. Trichomonas- CDC Fact Sheet. Center for Disease Control, USA (2008).Google Scholar
• 28  WHO. An overview of selected curable sexually transmitted diseases. Global Programme on AIDS Report 1995. WHO, Geneva, Switzerland (1995).Google Scholar
• 29  Van der Pol B. Trichomonas vaginalis infection: the most prevalent nonviral sexually transmitted infection receives the least public health attention. Clin. Infect. Dis.44(1),23–25 (2007).Crossref, Medline, Google Scholar
• 30  Gerbase AC, Rowley JT, Heymann DH, Berkley SF, Piot P. Global prevalence and incidence estimates of selected curable STDs. Sex Transm Infect.74(Suppl. 1),S12–S16 (1998).Medline, Google Scholar
• 31  WHO. Global Prevalence and Incidence of Selected Curable Sexually Transmitted Infections WHO, Geneva, Switzerland (2001)Google Scholar
• 32  Woolhouse ME, Gowtage-Sequeria S. Host range and emerging and reemerging pathogens. Emerging Infect. Dis.11(12),1842–1847 (2005).Crossref, Medline, Google Scholar
• 33  Rappelli P, Carta F, Delogu G et al.Mycoplasma hominis and Trichomonas vaginalis symbiosis: multiplicity of infection and transmissibility of M. hominis to human cells. Arch. Microbiol.175(1),70–74 (2001).Crossref, Medline, CAS, Google Scholar
• 34  Vancini RG, Pereira-Neves A, Borojevic R, Benchimol M. Trichomonas vaginalis harboring Mycoplasma hominis increases cytopathogenicity in vitro. Eur. J. Clin. Microbiol. Infect. Dis.27(4),259–267 (2008).Crossref, Medline, CAS, Google Scholar
• 35  Vancini RG, Benchimol M. Entry and intracellular location of Mycoplasma hominis in Trichomonas vaginalis. Arch. Microbiol.189(1),7–18 (2008).Crossref, Medline, CAS, Google Scholar
• 36  Ryan KJ, Ray CG, Sherris JC. Sherris Medical Microbiology: an Introduction to Infectious Diseases. McGraw-Hill, NY, USA (2004).Google Scholar
• 37  Talaro K, Talaro A. Foundations in Microbiology. Wm C Brown Dubuque, USA (1996).Google Scholar
• 38  Krasner RI. The Microbial Challenge: Human–Microbe Interactions. ASM Press, Washington, DC, USA (2002).Google Scholar
• 39  Sterling CR, Adam RD. The Pathogenic Enteric Protozoa: Giardia, Entamoeba, Cryptosporidium and Cyclospora.Kluwer Academic Publishers, Boston, MA, USA (2004).Google Scholar
• 40  Ecker DJ, Sampath R, Willett P et al. The microbial rosetta stone database: a compilation of global and emerging infectious microorganisms and bioterrorist threat agents. BMC Microbiol.5,19 (2005).Crossref, Medline, Google Scholar
• 41  WHO. WHO/Pan American Health Organization/UNESCO report of a consultation of experts on amoebiasis. Wkly Epidemiol. Rec.72,97–99 (1997).Medline, Google Scholar
• 42  WHO. WHO/PAHO/UNESCO report. A consultation with experts on amoebiasis. Mexico City, Mexico 28–29 January, 1997. Epidemiol. Bull.18,13–14 (1997).Google Scholar
• 43  Stanley SL Jr. Amoebiasis. Lancet361(9362),1025–1034 (2003).Crossref, Medline, CAS, Google Scholar
• 44  Heelan JS, Ingersoll FW. Essentials of Human Parasitology. Delmar Thomson Learning, Albany, NY, USA (2002).Google Scholar
• 45  Hung CC, Ko NY, Ko WC et al. Amoebiasis among patrons visiting gay saunas in Taiwan. HIV Med.9(9),787–789 (2008).Crossref, Medline, Google Scholar
• 46  Carlton JM, Hirt RP, Silva JC et al. Draft genome sequence of the sexually transmitted pathogen Trichomonas vaginalis. Science.315(5809),207–212 (2007).▪▪ The draft genome of this human parasite and a survey of the metabolic pathways and cellular biochemistry that is coded for in this parasite’s genome.Crossref, Medline, Google Scholar
• 47  Loftus B, Anderson I, Davies R et al. The genome of the protist parasite Entamoeba histolytica. Nature433(7028),865–868 (2005).▪▪ The genome of Entamoeba histolytica encodes a large number of novel receptor kinases and contains expansions of a variety of gene families, including those associated with virulence.Crossref, Medline, CAS, Google Scholar
• 48  Raether W, Hanel H. Nitroheterocyclic drugs with broad spectrum activity. Parasitol. Res.90(Suppl. 1),S19–S39 (2003).Crossref, Medline, Google Scholar
• 49  FDA. Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) US Department of Health, Washington, DC, USA (2008).Google Scholar
• 50  FDA. Electronic Orange Book Approved Drug Products with Therapeutic Equivalence Evaluations. US Department of Health and Human Services, DC, USA (2008).Google Scholar
• 51  CPS. Compendium of Pharmaceuticals and Specialities (CPS 2008). Canadian Pharmacists Association, Ottawa, Canada (2008).Google Scholar
• 52  Bendesky A, Menendez D, Ostrosky-Wegman P. Is metronidazole carcinogenic? Mutat. Res.511(2),133–144 (2002).Crossref, Medline, CAS, Google Scholar
• 53  Akyol D, Mungan T, Baltaci V. A comparative study of genotoxic effects in the treatment of Trichomonas vaginalis infection: metronidazole or nalidixic acid. Arch. Gynecol. Obstet.264(1),20–23 (2000).Crossref, Medline, CAS, Google Scholar
• 54  Edwards DI. Reduction of nitroimidazoles in vitro and DNA damage. Biochem. Pharmacol.35(1),53–58 (1986).Crossref, Medline, CAS, Google Scholar
• 55  Mansour TE. Chemotherapeutic Targets in Parasites. Cambridge University Press, Cambridge, UK (2002).Google Scholar
• 56  Lindmark DG, Muller M. Antitrichomonad action, mutagenicity, and reduction of metronidazole and other nitroimidazoles. Antimicrob. Agents Chemother.10(3),476–482 (1976).Crossref, Medline, CAS, Google Scholar
• 57  Muller M. Action of clinically utilized 5-nitroimidazoles on microorganisms. Scand. J. Infect. Dis. (Suppl. 26),S31–S41 (1981).Google Scholar
• 58  Muller M. Reductive activation of nitroimidazoles in anaerobic microorganisms. Biochem. Pharmacol.35(1),37–41 (1986).Crossref, Medline, CAS, Google Scholar
• 59  Docampo R. Sensitivity of parasites to free radical damage by antiparasitic drugs. Chem. Biol. Interact.73(1),1–27 (1990).Crossref, Medline, CAS, Google Scholar
• 60  Lloyd D, Pedersen JZ. Metronidazole radical anion generation in vivo in Trichomonas vaginalis: oxygen quenching is enhanced in a drug-resistant strain. J. Gen. Appl. Microbiol.131(1),87–92 (1985).CAS, Google Scholar
• 61  Johnson PJ. Metronidazole and drug resistance. Parasitol. Today (Regul. Ed.)9(5),183–186 (1993).Crossref, Medline, CAS, Google Scholar
• 62  Weksberg TE, Lynch GC, Krause KL, Pettitt BM. Molecular dynamics simulations of Trichomonas vaginalis ferredoxin show a loop-cap transition. Biophys. J.92(10),3337–3345 (2007).Crossref, Medline, CAS, Google Scholar
• 63  Yarlett N, Rowlands CC, Evans JC, Yarlett NC, Lloyd D. Nitroimidazole and oxygen derived radicals detected by electron spin resonance in hydrogenosomal and cytosolic fractions from Trichomonas vaginalis. Mol. Biochem. Parasitol.24(3),255–261 (1987).Crossref, Medline, CAS, Google Scholar
• 64  Crossnoe CR, Germanas JP, LeMagueres P, Mustata G, Krause KL. The crystal structure of Trichomonas vaginalis ferredoxin provides insight into metronidazole activation. J. Mol. Biol.318(2),503–518 (2002).Crossref, Medline, CAS, Google Scholar
• 65  Hrdy I, Cammack R, Stopka P, Kulda J, Tachezy J. Alternative pathway of metronidazole activation in Trichomonas vaginalis hydrogenosomes. Antimicrob. Agents Chemother.49(12),5033–5036 (2005).Crossref, Medline, CAS, Google Scholar
• 66  Hrdy I, Hirt RP, Dolezal P et al.Trichomonas hydrogenosomes contain the NADH dehydrogenase module of mitochondrial complex I. Nature432(7017),618–622 (2004).Crossref, Medline, CAS, Google Scholar
• 67  Tazreiter M, Leitsch D, Hatzenbichler E et al.Entamoeba histolytica: response of the parasite to metronidazole challenge on the levels of mRNA and protein expression. Exp. Parasitol.120(4),403–410 (2008).Crossref, Medline, CAS, Google Scholar
• 68  Quon DV, d’Oliveira CE, Johnson PJ. Reduced transcription of the ferredoxin gene in metronidazole-resistant Trichomonas vaginalis. Proc. Natl Acad. Sci. USA89(10),4402–4406 (1992).Crossref, Medline, CAS, Google Scholar
• 69  Crowell AL, Sanders-Lewis KA, Secor WE. In vitro metronidazole and tinidazole activities against metronidazole-resistant strains of Trichomonas vaginalis. Antimicrob. Agents Chemother.47(4),1407–1409 (2003).Crossref, Medline, CAS, Google Scholar
• 70  Dunne RL, Dunn LA, Upcroft P, O’Donoghue PJ, Upcroft JA. Drug resistance in the sexually transmitted protozoan Trichomonas vaginalis. Cell Res.13(4),239–249 (2003).Crossref, Medline, CAS, Google Scholar
• 71  Cudmore SL, Delgaty KL, Hayward-McClelland SF, Petrin DP, Garber GE. Treatment of infections caused by metronidazole-resistant Trichomonas vaginalis. Clin. Microbiol. Rev.17(4),783–793 (2004).Crossref, Medline, CAS, Google Scholar
• 72  Cohen CE, Desmond NM. Clinically resistant trichomoniasis. Sex Transm. Infect.81(2),181 (2005).Crossref, Medline, CAS, Google Scholar
• 73  Das S, Huengsberg M, Shahmanesh M. Treatment failure of vaginal trichomoniasis in clinical practice. Int. J. STD AIDS16(4),284–286 (2005).Crossref, Medline, Google Scholar
• 74  Bansal D, Malla N, Mahajan RC. Drug resistance in amoebiasis. Indian J. Med. Res.123(2),115–118 (2006).Medline, CAS, Google Scholar
• 75  Aggarwal A, Shier RM. Recalcitrant Trichomonas vaginalis infections successfully treated with vaginal acidification. J. Obstet. Gynaecol. Can.30(1),55–58 (2008).Crossref, Medline, Google Scholar
• 76  Hager WD. Treatment of metronidazole-resistant Trichomonas vaginalis with tinidazole: case reports of three patients. Sex. Transm. Dis.31(6),343–345 (2004).Crossref, Medline, Google Scholar
• 77  Samarawickrema NA, Brown DM, Upcroft JA, Thammapalerd N, Upcroft P. Involvement of superoxide dismutase and pyruvate:ferredoxin oxidoreductase in mechanisms of metronidazole resistance in Entamoeba histolytica. J. Antimicrob. Chemother.40(6),833–840 (1997).Crossref, Medline, CAS, Google Scholar
• 78  Wassmann C, Hellberg A, Tannich E, Bruchhaus I. Metronidazole resistance in the protozoan parasite Entamoeba histolytica is associated with increased expression of iron-containing superoxide dismutase and peroxiredoxin and decreased expression of ferredoxin 1 and flavin reductase. J. Biol. Chem.274(37),26051–26056 (1999).Crossref, Medline, CAS, Google Scholar
• 79  Wassmann C, Bruchhaus I. Superoxide dismutase reduces susceptibility to metronidazole of the pathogenic protozoan Entamoeba histolytica under microaerophilic but not under anaerobic conditions. Arch. Biochem. Biophys.376(1),236–238 (2000).Crossref, Medline, CAS, Google Scholar
• 80  Pal D, Banerjee S, Cui J, Schwartz A, Ghosh SK, Samuelson J. Giardia, Entamoeba, and Trichomonas enzymes activate metronidazole (nitroreductases) and inactivate metronidazole (NIMs). Antimicrob. Agents Chemother.53(2),458–464 (2009).▪ Reports that microaerophilic protists such as E. histolytica and T. vaginalis have bacteria-like enzymes capable of activating metronidazole (nitroreductases) and inactivating metronidazole (NIMs) and that these enzymes contribute to the overall toxicity of metronidazole to these parasites.Crossref, Medline, CAS, Google Scholar
• 81  Leitsch D, Kolarich D, Wilson IB, Altmann F, Duchene M. Nitroimidazole action in Entamoeba histolytica: a central role for thioredoxin reductase. PLoS Biol.5(8),211 (2007).▪▪ Very detailed and carefully undertaken investigation into the identification of the proteins that are modified by activated metronidazole.Crossref, Medline, Google Scholar
• 82  McMillan PJ, Patzewitz EM, Young SE et al. Differential inhibition of high and low Mr thioredoxin reductases of parasites by organotelluriums supports the concept that low Mr thioredoxin reductases are good drug targets. Parasitology1–7 (2008).Medline, Google Scholar
• 83  Rossignol JF, Kabil SM, El-Gohary Y, Younis AM. Nitazoxanide in the treatment of amoebiasis. Trans. R. Soc. Trop. Med. Hyg.101(10),1025–1031 (2007).Crossref, Medline, CAS, Google Scholar
• 84  Adagu IS, Nolder D, Warhurst DC, Rossignol JF. In vitro activity of nitazoxanide and related compounds against isolates of Giardia intestinalis, Entamoeba histolytica and Trichomonas vaginalis. J. Antimicrob. Chemother.49(1),103–111 (2002).Crossref, Medline, CAS, Google Scholar
• 85  Megraud F, Occhialini A, Rossignol JF. Nitazoxanide, a potential drug for eradication of Helicobacter pylori with no cross-resistance to metronidazole. Antimicrob. Agents Chemother.42(11),2836–2840 (1998).Crossref, Medline, CAS, Google Scholar
• 86  Sisson G, Goodwin A, Raudonikiene A et al. Enzymes associated with reductive activation and action of nitazoxanide, nitrofurans, and metronidazole in Helicobacter pylori. Antimicrob. Agents Chemother.46(7),2116–2123 (2002).Crossref, Medline, CAS, Google Scholar
• 87  Hoffman PS, Sisson G, Croxen MA et al. Antiparasitic drug nitazoxanide inhibits the pyruvate oxidoreductases of Helicobacter pylori, selected anaerobic bacteria and parasites, and Campylobacter jejuni. Antimicrob. Agents Chemother.51(3),868–876 (2007).▪▪ Description of the site of action of nitazoxanide that acts by a novel molecular mechanism. This information may lead to a new approach to the design of antiparasitic agents.Crossref, Medline, CAS, Google Scholar
• 88  Stipanuk MH. Metabolism of sulfur-containing amino acids. Annu. Rev. Nutr.6,179–209 (1986).Crossref, Medline, CAS, Google Scholar
• 89  Lockwood BC, Coombs GH. Purification and characterization of methionine γ-lyase from Trichomonas vaginalis. Biochem. J.279(Pt 3),675–682 (1991).Crossref, Medline, CAS, Google Scholar
• 90  Tokoro M, Asai T, Kobayashi S, Takeuchi T, Nozaki T. Identification and characterization of two isoenzymes of methionine γ-lyase from Entamoeba histolytica: a key enzyme of sulfur-amino acid degradation in an anaerobic parasitic protist that lacks forward and reverse trans-sulfuration pathways. J. Biol. Chem.278(43),42717–42727 (2003).Crossref, Medline, CAS, Google Scholar
• 91  Sato D, Yamagata W, Harada S, Nozaki T. Kinetic characterization of methionine γ-lyases from the enteric protozoan parasite Entamoeba histolytica against physiological substrates and trifluoromethionine, a promising lead compound against amoebiasis. FEBS J.275(3),548–560 (2008).Crossref, Medline, CAS, Google Scholar
• 92  Brown DM, Upcroft JA, Dodd HN, Chen N, Upcroft P. Alternative 2-keto acid oxidoreductase activities in Trichomonas vaginalis. Mol. Biochem. Parasitol.98(2),203–214 (1999).Crossref, Medline, CAS, Google Scholar
• 93  Bruchhaus I, Richter S, Tannich E. Recombinant expression and biochemical characterization of an NADPH:flavin oxidoreductase from Entamoeba histolytica. Biochem. J.330(3),1217–1221 (1998).Crossref, Medline, CAS, Google Scholar
• 94  Vicente JB, Ehrenkaufer GM, Saraiva LM, Teixeira M, Singh U. Entamoeba histolytica modulates a complex repertoire of novel genes in response to oxidative and nitrosative stress: implications for amebic pathogenesis. Cell. Microbiol.11(1),51–69 (2009).Crossref, Medline, CAS, Google Scholar
• 95  Coombs GH, Westrop GD, Suchan P et al. The amitochondriate eukaryote Trichomonas vaginalis contains a divergent thioredoxin-linked peroxiredoxin antioxidant system. J. Biol. Chem.279(7),5249–5256 (2004).Crossref, Medline, CAS, Google Scholar
• 96  Trussell RE. Microagglutination tests with Trichomonas vaginalis. J. Parasitol.32(6),563–569 (1946).Crossref, Medline, CAS, Google Scholar
• 97  Westrop GD, Goodall G, Mottram JC, Coombs GH. Cysteine biosynthesis in Trichomonas vaginalis involves cysteine synthase utilizing O-phosphoserine. J. Biol. Chem.281(35),25062–25075 (2006).Crossref, Medline, CAS, Google Scholar
• 98  Nozaki T, Tokoro M, Imada M et al. Cloning and biochemical characterization of genes encoding two isozymes of cysteine synthase from Entamoeba dispar. Mol. Biochem. Parasitol.107(1),129–133 (2000).Crossref, Medline, CAS, Google Scholar
• 99  Agren D, Schnell R, Oehlmann W, Singh M, Schneider G. Cysteine synthase (CysM) of Mycobacterium tuberculosis is an O-phosphoserine sulfhydrylase: evidence for an alternative cysteine biosynthesis pathway in mycobacteria. J. Biol. Chem.283(46),31567–31574 (2008).▪ Describes an alternative cysteine biosynthesis pathway.Crossref, Medline, Google Scholar
• 100  Burns KE, Baumgart S, Dorrestein PC, Zhai H, McLafferty FW, Begley TP. Reconstitution of a new cysteine biosynthetic pathway in Mycobacterium tuberculosis. J. Am. Chem. Soc.127(33),11602–11603 (2005).Crossref, Medline, CAS, Google Scholar
• 101  McKie AE, Edlind T, Walker J, Mottram JC, Coombs GH. The primitive protozoon Trichomonas vaginalis contains two methionine γ-lyase genes that encode members of the g-family of pyridoxal 5´-phosphate-dependent enzymes. J. Biol. Chem.273(10),5549–5556 (1998).Crossref, Medline, CAS, Google Scholar
• 102  Messerschmidt A, Worbs M, Steegborn C et al. Determinants of enzymatic specificity in the Cys-Met-metabolism PLP-dependent enzymes family: crystal structure of cystathionine γ-lyase from yeast and intrafamiliar structure comparison. Biol. Chem.384(3),373–386 (2003).Crossref, Medline, CAS, Google Scholar
• 103  Kudou D, Misaki S, Yamashita M et al. Structure of the antitumour enzyme L-methionine γ-lyase from Pseudomonas putida at 1.8 A resolution. J. Biochem. (Tokyo),141(4),535–544 (2007).Crossref, Medline, CAS, Google Scholar
• 104  Coombs GH, Mottram JC. Trifluoromethionine, a prodrug designed against methionine γ-lyase-containing pathogens, has efficacy in vitro and in vivo against Trichomonas vaginalis. Antimicrob. Agents Chemother.45(6),1743–1745 (2001).Crossref, Medline, CAS, Google Scholar
• 105  Alston TA, Bright HJ. Conversion of trifluoromethionine to a cross-linking agent by γ-cystathionase. Biochem. Pharmacol.32(5),947–950 (1983).Crossref, Medline, CAS, Google Scholar
• 106  Yoshimura M, Nakano Y, Koga T. L-methionine-γ-lyase, as a target to inhibit malodorous bacterial growth by trifluoromethionine. Biochem. Biophys. Res. Commun.292(4),964–968 (2002).Crossref, Medline, CAS, Google Scholar
• 107  Hussain S, Ali V, Jeelani G, Nozaki T. Isoform-dependent feedback regulation of serine O-acetyltransferase isoenzymes involved in l-cysteine biosynthesis of Entamoeba histolytica. Mol. Biochem. Parasitol.163(1),39–47 (2009).▪ The discovery of an isoform-dependent feedback regulatory system for a key enzyme in a cellular metabolic pathway in E. histolytica.Crossref, Medline, CAS, Google Scholar
• 108  Nozaki T, Asai T, Sanchez LB, Kobayashi S, Nakazawa M, Takeuchi T. Characterization of the gene encoding serine acetyltransferase, a regulated enzyme of cysteine biosynthesis from the protist parasites Entamoeba histolytica and Entamoeba dispar. Regulation and possible function of the cysteine biosynthetic pathway in Entamoeba. J. Biol. Chem.274(45),32445–32452 (1999).Crossref, Medline, CAS, Google Scholar
• 109  Francois JA, Kumaran S, Jez JM. Structural basis for interaction of O-acetylserine sulfhydrylase and serine acetyltransferase in the Arabidopsis cysteine synthase complex. Plant Cell18(12),3647–3655 (2006).Crossref, Medline, CAS, Google Scholar
• 110  Chinthalapudi K, Kumar M, Kumar S, Jain S, Alam N, Gourinath S. Crystal structure of native O-acetyl-serine sulfhydrylase from Entamoeba histolytica and its complex with cysteine: structural evidence for cysteine binding and lack of interactions with serine acetyl transferase. Proteins72(4),1222–1232 (2008).▪▪ Structural study of the E. histolytica enzyme O-acetyl-serine sulfhydrylase, one of the few enzymes from E. histolytica whose 3D structure has been determined and whose function is critical for sulfur metabolism in this parasite.Crossref, Medline, CAS, Google Scholar
• 111  Muller S, Liebau E, Walter RD, Krauth-Siegel RL. Thiol-based redox metabolism of protozoan parasites. Trends Parasitol.19(7),320–328 (2003).Crossref, Medline, CAS, Google Scholar
• 112  Agarwal SM, Jain R, Bhattacharya A, Azam A. Inhibitors of Escherichia coli serine acetyltransferase block proliferation of Entamoeba histolytica trophozoites. Int. J. Parasitol.38(2),137–141 (2008).Crossref, Medline, CAS, Google Scholar
• 113  Ueland PM. Pharmacological and biochemical aspects of S-adenosylhomocysteine and S-adenosylhomocysteine hydrolase. Pharmacol. Rev.34(3),223–253 (1982).Medline, CAS, Google Scholar
• 114  Chiang PK, Gordon RK, Tal J et al.S-Adenosylmethionine and methylation. FASEB J.10(4),471–480 (1996).Crossref, Medline, CAS, Google Scholar
• 115  Ctrnacta V, Stejskal F, Keithly JS, Hrdy I. Characterization of S-adenosylhomocysteine hydrolase from Cryptosporidium parvum. FEMS Microbiol. Lett.273(1),87–95 (2007).Crossref, Medline, CAS, Google Scholar
• 116  Minotto L, Ko GA, Edwards MR, Bagnara AS. Trichomonas vaginalis: expression and characterisation of recombinant S-adenosylhomocysteinase. Exp. Parasitol.90(2),175–180 (1998).Crossref, Medline, CAS, Google Scholar
• 117  Henderson DM, Hanson S, Allen T et al. Cloning of the gene encoding Leishmania donovani S-adenosylhomocysteine hydrolase, a potential target for antiparasitic chemotherapy. Mol. Biochem. Parasitol.53(1–2),169–183 (1992).Crossref, Medline, CAS, Google Scholar
• 118  Stanley SL Jr. The Entamoeba histolytica genome: something old, something new, something borrowed and sex too? Trends Parasitol.21(10),451–453 (2005).Crossref, Medline, CAS, Google Scholar
• 119  Reeves RE. Metabolism of Entamoeba histolytica Schaudinn, 1903. Adv. Parasitol.23,105–142 (1984).Crossref, Medline, CAS, Google Scholar
• 120  Rosenthal B, Mai Z, Caplivski D et al. Evidence for the bacterial origin of genes encoding fermentation enzymes of the amitochondriate protozoan parasite Entamoeba histolytica. J. Bacteriol.179(11),3736–3745 (1997).Crossref, Medline, CAS, Google Scholar
• 121  Ochman H, Lawrence JG, Groisman EA. Lateral gene transfer and the nature of bacterial innovation. Nature405(6784),299–304 (2000).Crossref, Medline, CAS, Google Scholar
• 122  Andersson JO, Hirt RP, Foster PG, Roger AJ. Evolution of four gene families with patchy phylogenetic distributions: influx of genes into protist genomes. BMC Evol. Biol.6,27 (2006).Crossref, Medline, Google Scholar
• 123  Samuelson J. Why metronidazole is active against both bacteria and parasites. Antimicrob. Agents Chemother.43(7),1533–1541 (1999).Crossref, Medline, CAS, Google Scholar
• 124  van Grinsven KW, Rosnowsky S, van Weelden SW et al. Acetate:succinate CoA-transferase in the hydrogenosomes of Trichomonas vaginalis: identification and characterization. J. Biol. Chem.283(3),1411–1418 (2008).Crossref, Medline, CAS, Google Scholar
• 125  Mentel M, Zimorski V, Haferkamp P, Martin W, Henze K. Protein import into hydrogenosomes of Trichomonas vaginalis involves both N-terminal and internal targeting signals: a case study of thioredoxin reductases. Eukaryotic Cell7(10),1750–1757 (2008).Crossref, Medline, CAS, Google Scholar
• 126  Smutna T, Goncalves VL, Saraiva LM, Tachezy J, Teixeira M, Hrdy I. Flavodiiron protein from Trichomonas vaginalis hydrogenosomes: the terminal oxygen reductase. Eukaryotic Cell8,47–55 (2009).Crossref, Medline, CAS, Google Scholar
• 127  Benchimol M. The hydrogenosome as a drug target. Curr. Pharm. Des.14(9),872–881 (2008).▪ Important review that has surveyed the critical nature of the Trichomonas vaginalis hydrogenosome and the compounds that can affect its function.Crossref, Medline, CAS, Google Scholar
• 128  Sen A, Chatterjee NS, Akbar MA, Nandi N, Das P. The 29-kilodalton thiol-dependent peroxidase of Entamoeba histolytica is a factor involved in pathogenesis and survival of the parasite during oxidative stress. Eukaryotic Cell6(4),664–673 (2007).Crossref, Medline, CAS, Google Scholar
• 129  Tovar J, Fischer A, Clark CG. The mitosome, a novel organelle related to mitochondria in the amitochondrial parasite Entamoeba histolytica. Mol. Microbiol.32(5),1013–1021 (1999).Crossref, Medline, CAS, Google Scholar
• 130  Chan KW, Slotboom DJ, Cox S et al. A novel ADP/ATP transporter in the mitosome of the microaerophilic human parasite Entamoeba histolytica. Curr. Biol.15(8),737–742 (2005).Crossref, Medline, CAS, Google Scholar
• 131  Aguilera P, Barry T, Tovar J. Entamoeba histolytica mitosomes: organelles in search of a function. Exp. Parasitol.118(1),10–16 (2008).Crossref, Medline, CAS, Google Scholar
• 132  Rinaldo-Matthis A, Wing C, Ghanem M et al. Inhibition and structure of Trichomonas vaginalis purine nucleoside phosphorylase with picomolar transition state analogues. Biochemistry46(3),659–668 (2007).Crossref, Medline, CAS, Google Scholar
• 133  Jhingran A, Padmanabhan PK, Singh S et al. Characterization of the Entamoeba histolytica ornithine decarboxylase-like enzyme. PLoS Negl. Trop. Dis.2(1),115 (2008).Crossref, Google Scholar
• 134  Singh S, Malik BK, Sharma DK. Molecular modeling and docking analysis of Entamoeba histolytica glyceraldehyde-3 phosphate dehydrogenase, a potential target enzyme for anti-protozoal drug development. Chem. Biol. Drug Des.71(6),554–562 (2008).Crossref, Medline, CAS, Google Scholar
• 135  Stephen P, Vijayan R, Bhat A, Subbarao N, Bamezai RN. Molecular modeling on pyruvate phosphate dikinase of Entamoeba histolytica and in silico virtual screening for novel inhibitors. J. Comput. Aided Mol. Des.22(9),647–660 (2008).Crossref, Medline, CAS, Google Scholar
• 136  Singh S, Malik BK, Sharma DK. Choke point analysis of metabolic pathways in E. histolytica: a computational approach for drug target identification. Bioinformation2(2),68–72 (2007).Crossref, Medline, Google Scholar
• 137  Saavedra E, Marin-Hernandez A, Encalada R, Olivos A, Mendoza-Hernandez G, Moreno-Sanchez R. Kinetic modeling can describe in vivo glycolysis in Entamoeba histolytica. FEBS J.274(18),4922–4940 (2007).Crossref, Medline, CAS, Google Scholar
• 138  Huang KY, Chien KY, Lin YC et al. A proteome reference map of Trichomonas vaginalis. Parasitol. Res.104(4),927–933 (2009).Crossref, Medline, Google Scholar
• 139  Ehrenkaufer GM, Singh U. Transcriptional regulatory networks in Entamoeba histolytica. Curr. Drug Targets9(11),931–937 (2008).Crossref, Medline, CAS, Google Scholar
• 140  Anamika K, Bhattacharya A, Srinivasan N. Analysis of the protein kinome of Entamoeba histolytica. Proteins71(2),995–1006 (2008).Crossref, Medline, CAS, Google Scholar
• 141  Singh U, Ehrenkaufer GM. Recent insights into Entamoeba development: identification of transcriptional networks associated with stage conversion. Int. J. Parasitol.39,41–47 (2009).Crossref, Medline, CAS, Google Scholar
• 142  Ehrenkaufer GM, Haque R, Hackney JA, Eichinger DJ, Singh U. Identification of developmentally regulated genes in Entamoeba histolytica: insights into mechanisms of stage conversion in a protozoan parasite. Cell. Microbiol.9(6),1426–1444 (2007).Crossref, Medline, CAS, Google Scholar
• 143  Navaneethan U, Giannella RA. Mechanisms of infectious diarrhea. Nat. Clin. Pract. Gastroenterol. Hepatol.5(11),637–647 (2008).Crossref, Medline, Google Scholar
• 144  Mirelman D, Anbar M, Bracha R. Epigenetic transcriptional gene silencing in Entamoeba histolytica. IUBMB Life60(9),598–604 (2008).Crossref, Medline, CAS, Google Scholar
• 145  Mirelman D, Anbar M, Bracha R. Trophozoites of Entamoeba histolytica epigenetically silenced in several genes are virulence-attenuated. Parasite15(3),266–274 (2008).Crossref, Medline, CAS, Google Scholar
• 146  Huston CD, Petri WA Jr. Host–pathogen interaction in amebiasis and progress in vaccine development. Eur. J. Clin. Microbiol. Infect. Dis.17(9),601–614 (1998).Crossref, Medline, CAS, Google Scholar
• 147  Okada M, Huston CD, Mann BJ, Petri WA Jr, Kita K, Nozaki T. Proteomic analysis of phagocytosis in the enteric protozoan parasite Entamoeba histolytica. Eukaryotic Cell4(4),827–831 (2005).Crossref, Medline, CAS, Google Scholar
• 148  Gilchrist CA, Petri WA. Virulence factors of Entamoeba histolytica. Curr. Opin. Microbiol.2(4),433–437 (1999).Crossref, Medline, CAS, Google Scholar
• 149  Boettner DR, Petri WA. Entamoeba histolytica activates host cell caspases during contact-dependent cell killing. Curr. Top. Microbiol. Immunol.289,175–184 (2005).Medline, CAS, Google Scholar
• 150  Mann BJ. Structure and function of the Entamoeba histolytica Gal/GalNAc lectin. Int. Rev. Cytol.216,59–80 (2002).Crossref, Medline, CAS, Google Scholar
• 151  Dodson JM, Lenkowski PW Jr, Eubanks AC et al. Infection and immunity mediated by the carbohydrate recognition domain of the Entamoeba histolytica Gal/GalNAc lectin. J. Infect. Dis.179(2),460–466 (1999).Crossref, Medline, CAS, Google Scholar
• 152  Cheng XJ, Tsukamoto H, Kaneda Y, Tachibana H. Identification of the 150-kDa surface antigen of Entamoeba histolytica as a galactose- and N-acetyl-D-galactosamine-inhibitable lectin. Parasitol. Res.84(8),632–639 (1998).Crossref, Medline, CAS, Google Scholar
• 153  Pillai DR, Wan PS, Yau YC, Ravdin JI, Kain KC. The cysteine-rich region of the Entamoeba histolytica adherence lectin (170-kilodalton subunit) is sufficient for high-affinity Gal/GalNAc-specific binding in vitro. Infect. Immun.67(8),3836–3841 (1999).Crossref, Medline, CAS, Google Scholar
• 154  Mittal K, Welter BH, Temesvari LA. Entamoeba histolytica: lipid rafts are involved in adhesion of trophozoites to host extracellular matrix components. Exp. Parasitol.120(2),127–134 (2008).Crossref, Medline, CAS, Google Scholar
• 155  Marion S, Tavares P, Arhets P, Guillen N. Signal transduction through the Gal–GalNAc lectin of Entamoeba histolytica involves a spectrin-like protein. Mol. Biochem. Parasitol.135(1),31–38 (2004).Crossref, Medline, CAS, Google Scholar
• 156  Vats D, Vishwakarma RA, Bhattacharya S, Bhattacharya A. Reduction of cell surface glycosylphosphatidylinositol conjugates in Entamoeba histolytica by antisense blocking of E. histolytica GlcNAc-phosphatidylinositol deacetylase expression: effect on cell proliferation, endocytosis, and adhesion to target cells. Infect. Immun.73(12),8381–8392 (2005).Crossref, Medline, CAS, Google Scholar
• 157  Seigneur M, Mounier J, Prevost MC, Guillen N. A lysine- and glutamic acid-rich protein, KERP1, from Entamoeba histolytica binds to human enterocytes. Cell. Microbiol.7(4),569–579 (2005).Crossref, Medline, CAS, Google Scholar
• 158  Santi-Rocca J, Weber C, Guigon G, Sismeiro O, Coppee J-Y, Guillen N. The lysine- and glutamic acid-rich protein KERP1 plays a role in Entamoeba histolytica liver abscess pathogenesis. Cell. Microbiol.10(1),202–217 (2008).Medline, CAS, Google Scholar
• 159  Winkelmann J, Leippe M, Bruhn H. A novel saposin-like protein of Entamoeba histolytica with membrane-fusogenic activity. Mol. Biochem. Parasitol.147(1),85–94 (2006).Crossref, Medline, CAS, Google Scholar
• 160  Zhang X, Zhang Z, Alexander D, Bracha R, Mirelman D, Stanley SL Jr. Expression of amoebapores is required for full expression of Entamoeba histolytica virulence in amebic liver abscess but is not necessary for the induction of inflammation or tissue damage in amebic colitis. Infect. Immun.72(2),678–683 (2004).Crossref, Medline, CAS, Google Scholar
• 161  Hecht O, Van Nuland NA, Schleinkofer K et al. Solution structure of the pore-forming protein of Entamoeba histolytica. J. Biol. Chem.279(17),17834–17841 (2004).Crossref, Medline, CAS, Google Scholar
• 162  Leippe M, Bruhn H, Hecht O, Grotzinger J. Ancient weapons: the three-dimensional structure of amoebapore A. Trends Parasitol.21(1),5–7 (2005).Crossref, Medline, CAS, Google Scholar
• 163  Tran VQ, Herdman DS, Torian BE, Reed SL. The neutral cysteine proteinase of Entamoeba histolytica degrades IgG and prevents its binding. J. Infect. Dis.177(2),508–511 (1998).Crossref, Medline, CAS, Google Scholar
• 164  Garcia-Nieto RM, Rico-Mata R, Arias-Negrete S, Avila EE. Degradation of human secretory IgA1 and IgA2 by Entamoeba histolytica surface-associated proteolytic activity. Parasitol. Int.57(4),417–423 (2008).Crossref, Medline, CAS, Google Scholar
• 165  Que X, Reed SL. Cysteine proteinases and the pathogenesis of amebiasis. Clin. Microbiol. Rev.13(2),196–206 (2000).Crossref, Medline, CAS, Google Scholar
• 166  Tillack M, Biller L, Irmer H et al. The Entamoeba histolytica genome: primary structure and expression of proteolytic enzymes. BMC Genomics8,170 (2007).Crossref, Medline, Google Scholar
• 167  Olivos-Garcia A, Tello E, Nequiz-Avendano M et al. Cysteine proteinase activity is required for survival of the parasite in experimental acute amoebic liver abscesses in hamsters. Parasitology129(1),19–25 (2004).Crossref, Medline, CAS, Google Scholar
• 168  Hellberg A, Nickel R, Lotter H, Tannich E, Bruchhaus I. Overexpression of cysteine proteinase 2 in Entamoeba histolytica or Entamoeba dispar increases amoeba-induced monolayer destruction in vitro but does not augment amoebic liver abscess formation in gerbils. Cell. Microbiol.3(1),13–20 (2001).Crossref, Medline, CAS, Google Scholar
• 169  Que X, Brinen LS, Perkins P et al. Cysteine proteinases from distinct cellular compartments are recruited to phagocytic vesicles by Entamoeba histolytica. Mol. Biochem. Parasitol.119(1),23–32 (2002).Crossref, Medline, CAS, Google Scholar
• 170  Singh D, Naik SR, Naik S. Contact of Entamoeba histolytica with baby hamster kidney-21 (BHK-21) cell line on cysteine proteinase activity. Indian J. Med. Res.119(4),157–161 (2004).Medline, Google Scholar
• 171  Singh D, Naik SR, Naik S. Role of cysteine proteinase of Entamoeba histolytica in target cell death. Parasitology129(2),127–135 (2004).Crossref, Medline, CAS, Google Scholar
• 172  Spinella S, Levavasseur E, Petek F, Rigothier MC. Purification and biochemical characterization of a novel cysteine protease of Entamoeba histolytica. Eur. J. Biochem.266(1),170–180 (1999).Crossref, Medline, CAS, Google Scholar
• 173  Ocadiz R, Orozco E, Carrillo E et al. EhCP112 is an Entamoeba histolytica secreted cysteine protease that may be involved in the parasite-virulence. Cell. Microbiol.7(2),221–232 (2005).Crossref, Medline, CAS, Google Scholar
• 174  Garcia-Rivera G, Rodriguez MA, Ocadiz R et al.Entamoeba histolytica: a novel cysteine protease and an adhesin form the 112 kDa surface protein. Mol. Microbiol.33(3),556–568 (1999).Crossref, Medline, CAS, Google Scholar
• 175  Banuelos C, Garcia-Rivera G, Lopez-Reyes I, Orozco E. Functional characterization of EhADH112: an Entamoeba histolytica Bro1 domain-containing protein. Exp. Parasitol.110(3),292–297 (2005).Crossref, Medline, CAS, Google Scholar
• 176  Petri WA Jr, Haque R, Mann BJ. The bittersweet interface of parasite and host: lectin-carbohydrate interactions during human invasion by the parasite Entamoeba histolytica. Annu. Rev. Microbiol.56,39–64 (2002).▪ Excellent review on lectin–carbohydrate interactions during human invasion by the parasite E. histolytica. The structure and function of the lectin that controls induced cell biologic processes are discussed.Crossref, Medline, CAS, Google Scholar
• 177  Rawal S, Majumdar S, Vohra H. Activation of MAPK kinase pathway by Gal/GalNAc adherence lectin of E. histolytica: gateway to host response. Mol. Cell. Biochem.268(1–2),93–101 (2005).▪▪ Indicates that activation of the MAPK cascade is implicated in a variety of physiological cellular functions including apoptosis, proliferation, cytoskeleton rearrangements and permeability changes during host–pathogen interactions of E. histolytica .Crossref, Medline, CAS, Google Scholar
• 178  Pillai DR, Kain KC. Entamoeba histolytica: identification of a distinct β₂ integrin-like molecule with a potential role in cellular adherence. Exp. Parasitol.109(3),135–142 (2005).Crossref, Medline, CAS, Google Scholar
• 179  Sim S, Park S-J, Yong T-S, Im K-I, Shin MH. Involvement of β₂-integrin in ROS-mediated neutrophil apoptosis induced by Entamoeba histolytica. Microbes Infect.9(11),1368–1375 (2007).Crossref, Medline, CAS, Google Scholar
• 180  Sim S, Yong TS, Park SJ et al. NADPH oxidase-derived reactive oxygen species-mediated activation of ERK1/2 is required for apoptosis of human neutrophils induced by Entamoeba histolytica. J. Immunol.174(7),4279–4288 (2005).Crossref, Medline, CAS, Google Scholar
• 181  Kim KA, Lee YA, Shin MH. Calpain-dependent calpastatin cleavage regulates caspase-3 activation during apoptosis of Jurkat T cells induced by Entamoeba histolytica. Int. J. Parasitol.37(11),1209–1219 (2007).Crossref, Medline, CAS, Google Scholar
• 182  Vines RR, Ramakrishnan G, Rogers JB, Lockhart LA, Mann BJ, Petri WA Jr. Regulation of adherence and virulence by the Entamoeba histolytica lectin cytoplasmic domain, which contains a β₂ integrin motif. Mol. Biol. Cell9(8),2069–2079 (1998).Crossref, Medline, CAS, Google Scholar
• 183  Godbold GD, Mann BJ. Involvement of the actin cytoskeleton and p21rho-family GTPases in the pathogenesis of the human protozoan parasite Entamoeba histolytica. Braz. J. Med. Biol. Res.31(8),1049–1058 (1998).Crossref, Medline, CAS, Google Scholar
• 184  Franco E, Manning-Cela R, Meza I. Signal transduction in Entamoeba histolytica induced by interaction with fibronectin: presence and activation of phosphokinase A and its possible relation to invasiveness. Arch. Med. Res.33(4),389–397 (2002).Crossref, Medline, CAS, Google Scholar
• 185  Franco-Barraza J, Zamudio-Meza H, Franco E, del Carmen Dominguez-Robles M, Villegas-Sepulveda N, Meza I. Rho signaling in Entamoeba histolytica modulates actomyosin-dependent activities stimulated during invasive behavior. Cell Motil. Cytoskeleton63(3),117–131 (2006).Crossref, Medline, CAS, Google Scholar
• 186  Arias-Romero LE, de la Rosa CH, Almaraz-Barrera Mde J, Diaz-Valencia JD, Sosa-Peinado A, Vargas M. EhGEF3, a novel Dbl family member, regulates EhRacA activation during chemotaxis and capping in Entamoeba histolytica. Cell Motil. Cytoskeleton64(5),390–404 (2007).Crossref, Medline, CAS, Google Scholar
• 187  Arias-Romero LE, de Jesus Almaraz-Barrera M, Diaz-Valencia JD, Rojo-Dominguez A, Hernandez-Rivas R, Vargas M. EhPAK2, a novel p21-activated kinase, is required for collagen invasion and capping in Entamoeba histolytica. Mol. Biochem. Parasitol.149(1),17–26 (2006).Crossref, Medline, CAS, Google Scholar
• 188  Labruyere E, Guillen N. Host tissue invasion by Entamoeba histolytica is powered by motility and phagocytosis. Arch. Med. Res.37(2),253–258 (2006).Crossref, Medline, CAS, Google Scholar
• 189  Blazquez S, Guigon G, Weber C et al. Chemotaxis of Entamoeba histolytica towards the pro-inflammatory cytokine TNF is based on PI3K signalling, cytoskeleton reorganization and the galactose/N-acetylgalactosamine lectin activity. Cell. Microbiol.10(8),1676–1686 (2008).Crossref, Medline, CAS, Google Scholar
• 190  Picazarri K, Luna-Arias JP, Carrillo E, Orozco E, Rodriguez MA. Entamoeba histolytica: identification of EhGPCR-1, a novel putative G protein-coupled receptor that binds to EhRabB. Exp. Parasitol.110(3),253–258 (2005).Crossref, Medline, CAS, Google Scholar
• 191  Rios A, Hernandez-Ramirez VI, Moguel M et al. Participation of Rho, ROCK-2, and GAP activities during actin microfilament rearrangements in Entamoeba histolytica induced by fibronectin signaling. Cell Biol. Int.32(8),984–1000 (2008).Crossref, Medline, CAS, Google Scholar
• 192  Lotter H, Tannich E. The current status of an amebiasis vaccine. Arch. Med. Res.37(2),292–296 (2006).Crossref, Medline, CAS, Google Scholar
• 193  Stanley SL Jr. Vaccines for amoebiasis: barriers and opportunities. Parasitology133(Suppl.),S81–S86 (2006).Crossref, Medline, Google Scholar
• 194  Snow MJ, Stanley SL Jr. Recent progress in vaccines for amebiasis. Arch. Med. Res.37(2),280–286 (2006).Crossref, Medline, CAS, Google Scholar
• 195  Carrero JC, Cervantes-Rebolledo C, Aguilar-Diaz H, Diaz-Gallardo MY, Laclette JP, Morales-Montor J. The role of the secretory immune response in the infection by Entamoeba histolytica. Parasite Immunol.29(7),331–338 (2007).Crossref, Medline, CAS, Google Scholar
• 196  Petri WA. Entamoeba histolytica: clinical update and vaccine prospects. Curr. Infect. Dis. Rep.4(2),124–129 (2002).Crossref, Medline, Google Scholar
• 197  Chaudhry OA, Petri WA Jr. Vaccine prospects for amebiasis. Expert Rev. Vaccines4(5),657–668 (2005).Crossref, Medline, CAS, Google Scholar
• 198  Petri WA Jr, Chaudhry O, Haque R, Houpt E. Adherence-blocking vaccine for amebiasis. Arch. Med. Res.37(2),288–291 (2006).Crossref, Medline, CAS, Google Scholar
• 199  Houpt E, Barroso L, Lockhart L et al. Prevention of intestinal amebiasis by vaccination with the Entamoeba histolytica Gal/GalNac lectin. Vaccine22(5–6),611–617 (2004).Crossref, Medline, CAS, Google Scholar
• 200  Tachibana H, Watanabe K, Cheng XJ et al. VH3 gene usage in neutralizing human antibodies specific for the Entamoeba histolytica Gal/GalNAc lectin heavy subunit. Infect. Immun.71(8),4313–4319 (2003).Crossref, Medline, CAS, Google Scholar
• 201  Tachibana H, Cheng XJ, Tsukamoto H, Itoh J. Characterization of Entamoeba histolytica intermediate subunit lectin-specific human monoclonal antibodies generated in transgenic mice expressing human immunoglobulin loci. Infect. Immun.77(1),549–556 (2009).Crossref, Medline, CAS, Google Scholar
• 202  Campbell D, Mann BJ, Chadee K. A subunit vaccine candidate region of the Entamoeba histolytica galactose-adherence lectin promotes interleukin-12 gene transcription and protein production in human macrophages. Eur. J. Immunol.30(2),423–430 (2000).Crossref, Medline, CAS, Google Scholar
• 203  Mann BJ, Lockhart LA. Molecular analysis of the Gal/GalNAc adhesin of Entamoeba histolytica. J. Eukaryot. Microbiol.45(2),S13–S16 (1998).Crossref, Google Scholar
• 204  Guerrero-Manriquez GG, Sanchez-Ibarra F, Avila EE. Inhibition of Entamoeba histolytica proteolytic activity by human salivary IgA antibodies. APMIS106(11),1088–1094 (1998).Crossref, Medline, CAS, Google Scholar
• 205  MacFarlane RC, Singh U. Identification of an Entamoeba histolytica serine-, threonine-, and isoleucine-rich protein with roles in adhesion and cytotoxicity. Eukaryotic Cell6(11),2139–2146 (2007).Crossref, Medline, CAS, Google Scholar
• 206  Mehra A, Bhattacharya S, Bhattacharya A. Identification and functional characterization of a novel lysine-rich protein from Entamoeba histolytica. Am. J. Biochem. Biotech.3(4),193–198 (2007).Crossref, CAS, Google Scholar
• 207  Cheng XJ, Tachibana H. Protection of hamsters from amebic liver abscess formation by immunization with the 150- and 170-kDa surface antigens of Entamoeba histolytica. Parasitol. Res.87(2),126–130 (2001).Crossref, Medline, CAS, Google Scholar
• 208  Ventura-Juarez J, Campos-Rodriguez R, Jarillo-Luna RA et al. Trophozoites of Entamoeba histolytica express a CD59-like molecule in human colon. Parasitol. Res.104(4),821–826 (2009).Crossref, Medline, CAS, Google Scholar
• 209  Boettner DR, Huston CD, Linford AS et al.Entamoeba histolytica phagocytosis of human erythrocytes involves PATMK, a member of the transmembrane kinase family. PLoS Pathog.4(1),8 (2008).Crossref, Google Scholar
• 210  Gaucher D, Chadee K. Construction and immunogenicity of a codon-optimized Entamoeba histolytica Gal-lectin-based DNA vaccine. Vaccine20(27–28),3244–3253 (2002).Crossref, Medline, CAS, Google Scholar
• 211  Zhang T, Stanley SL Jr. DNA vaccination with the serine rich Entamoeba histolytica protein (SREHP) prevents amebic liver abscess in rodent models of disease. Vaccine18(9–10),868–874 (1999).Crossref, Medline, CAS, Google Scholar
• 212  Hirt RP, Noel CJ, Sicheritz-Ponten T, Tachezy J, Fiori PL. Trichomonas vaginalis surface proteins: a view from the genome. Trends Parasitol.23(11),540–547 (2007).Crossref, Medline, CAS, Google Scholar
• 213  Engbring JA, Alderete JF. Characterization of Trichomonas vaginalis AP33 adhesin and cell surface interactive domains. Microbiology144 (Pt 11),3011–3018 (1998).Crossref, Medline, CAS, Google Scholar
• 214  Engbring JA, Alderete JF. Three genes encode distinct AP33 proteins involved in Trichomonas vaginalis cytoadherence. Mol. Microbiol.28(2),305–313 (1998).Crossref, Medline, CAS, Google Scholar
• 215  Kucknoor AS, Mundodi V, Alderete JF. Heterologous expression in Tritrichomonas foetus of functional Trichomonas vaginalis AP65 adhesin. BMC Mol. Biol.6(1),5 (2005).Crossref, Medline, Google Scholar
• 216  Ong S-J, Hsu H-M, Liu H-W, Chu C-H, Tai J-H. Multifarious transcriptional regulation of adhesion protein gene ap65-1 by a novel Myb1 protein in the protozoan parasite Trichomonas vaginalis. Eukaryotic Cell5(2),391–399 (2006).Crossref, Medline, CAS, Google Scholar
• 217  Singh BN, Hayes GR, Lucas JJ et al. Structural details and composition of Trichomonas vaginalis lipophosphoglycan in relevance to the epithelial immune function. Glycoconj. J.26(1),3–17 (2009).Crossref, Medline, CAS, Google Scholar
• 218  Mundodi V, Kucknoor AS, Alderete JF. Immunogenic and plasminogen-binding surface-associated a-enolase of Trichomonas vaginalis. Infect. Immun.76(2),523–531 (2008).Crossref, Medline, CAS, Google Scholar
• 219  Mundodi V, Kucknoor AS, Chang TH, Alderete JF. A novel surface protein of Trichomonas vaginalis is regulated independently by low iron and contact with vaginal epithelial cells. BMC Microbiol.6,6 (2006).Crossref, Medline, CAS, Google Scholar
• 220  Addis MF, Rappelli P, Pinto De Andrade AM et al. Identification of Trichomonas vaginalis α-actinin as the most common immunogen recognized by sera of women exposed to the parasite. J. Infect. Dis.180(5),1727–1730 (1999).Crossref, Medline, CAS, Google Scholar
• 221  Leon-Felix J, Ortega-Lopez J, Orozco-Solis R, Arroyo R. Two novel asparaginyl endopeptidase-like cysteine proteinases from the protist Trichomonas vaginalis: their evolutionary relationship within the clan CD cysteine proteinases. Gene335,25–35 (2004).Crossref, Medline, CAS, Google Scholar
• 222  Sommer U, Costello CE, Hayes GR et al. Identification of Trichomonas vaginalis cysteine proteases that induce apoptosis in human vaginal epithelial cells. J. Biol. Chem.280(25),23853–23860 (2005).Crossref, Medline, CAS, Google Scholar
• 223  Kummer S, Hayes GR, Gilbert RO, Beach DH, Lucas JJ, Singh BN. Induction of human host cell apoptosis by Trichomonas vaginalis cysteine proteases is modulated by parasite exposure to iron. Microb. Pathog.44(3),197–203 (2008).Crossref, Medline, CAS, Google Scholar
• 224  Mendoza-Lopez MR, Becerril-Garcia C, Fattel-Facenda LV et al. CP30, a cysteine proteinase involved in Trichomonas vaginalis cytoadherence. Infect. Immun.68(9),4907–4912 (2000).Crossref, Medline, CAS, Google Scholar
• 225  Yadav M, Dubey ML, Gupta I, Malla N. Cysteine proteinase 30 (CP30) and antibody response to CP30 in serum and vaginal washes of symptomatic and asymptomatic Trichomonas vaginalis-infected women. Parasite Immunol.29(7),359–365 (2007).Crossref, Medline, CAS, Google Scholar
• 226  Alvarez-Sanchez ME, Avila-Gonzalez L, Becerril-Garcia C, Fattel-Facenda LV, Ortega-Lopez J, Arroyo R. A novel cysteine proteinase (CP65) of Trichomonas vaginalis involved in cytotoxicity. Microb. Pathog.28(4),193–202 (2000).Crossref, Medline, CAS, Google Scholar
• 227  Solano-Gonzalez E, Alvarez-Sanchez ME, Avila-Gonzalez L, Rodriguez-Vargas VH, Arroyo R, Ortega-Lopez J. Location of the cell-binding domain of CP65, a 65kDa cysteine proteinase involved in Trichomonas vaginalis cytotoxicity. Int. J. Biochem. Cell Biol.38(12),2114–2127 (2006).Crossref, Medline, CAS, Google Scholar
• 228  Leon-Sicairos CR, Leon-Felix J, Arroyo R. tvcp12: a novel Trichomonas vaginalis cathepsin L-like cysteine proteinase-encoding gene. Microbiology150(5),1131–1138 (2004).Crossref, Medline, CAS, Google Scholar
• 229  Hernandez-Gutierrez R, Avila-Gonzalez L, Ortega-Lopez J, Cruz-Talonia F, Gomez-Gutierrez G, Arroyo R. Trichomonas vaginalis: characterization of a 39-kDa cysteine proteinase found in patient vaginal secretions. Exp. Parasitol.107(3–4),125–135 (2004).Crossref, Medline, CAS, Google Scholar
• 230  Irvine JW, North MJ, Coombs GH. Use of inhibitors to identify essential cysteine proteinases of Trichomonas vaginalis. FEMS Microbiol. Lett.149(1),45–50 (1997).Crossref, Medline, CAS, Google Scholar
• 231  Fiori PL, Rappelli P, Addis MF, Mannu F, Cappuccinelli P. Contact-dependent disruption of the host cell membrane skeleton induced by Trichomonas vaginalis. Infect. Immun.65(12),5142–5148 (1997).Crossref, Medline, CAS, Google Scholar
• 232  Kucknoor AS, Mundodi V, Alderete JF. Adherence to human vaginal epithelial cells signals for increased expression of Trichomonas vaginalis genes. Infect. Immun.73(10),6472–6478 (2005).Crossref, Medline, CAS, Google Scholar
• 233  Garcia AF, Chang TH, Benchimol M, Klumpp DJ, Lehker MW, Alderete JF. Iron and contact with host cells induce expression of adhesins on surface of Trichomonas vaginalis. Mol. Microbiol.47(5),1207–1224 (2003).Crossref, Medline, CAS, Google Scholar
• 234  Chang JH, Ryang YS, Kim SK, Park JY. Trichomonas vaginalis-induced apoptosis in RAW264.7 cells is regulated through Bcl-xL, but not Bcl-2. Parasite Immunol.26(3),141–150 (2004).Crossref, Medline, CAS, Google Scholar
• 235  Ryang YS, Chang JH, Park JY. Involvement of MAP kinases in apoptosis of macrophage treated with Trichomonas vaginalis. Yonsei Med. J.45(4),751–754 (2004).Crossref, Medline, CAS, Google Scholar
• 236  Madeiro da Costa RF, de Souza W, Benchimol M, Alderete JF, Morgado-Diaz JA. Trichomonas vaginalis perturbs the junctional complex in epithelial cells. Cell Res.15(9),704–716 (2005).Crossref, Medline, CAS, Google Scholar
• 237  Zubacova Z, Cimburek Z, Tachezy J. Comparative analysis of trichomonad genome sizes and karyotypes. Mol. Biochem. Parasitol.161(1),49–54 (2008).Crossref, Medline, CAS, Google Scholar
• 238  Cegelski L, Marshall GR, Eldridge GR, Hultgren SJ. The biology and future prospects of antivirulence therapies. Nat. Rev. Microbiol.6(1),17–27 (2008).Crossref, Medline, CAS, Google Scholar
• 239  Baxt LA, Singh U. New insights into Entamoeba histolytica pathogenesis. Curr. Opin. Infect. Dis.21(5),489–494 (2008).Crossref, Medline, Google Scholar
• 240  WHO. Global prevalence and incidence of selected curable sexually transmitted infections: overview and estimates. World Health Organization, Geneva, Switzerland (2001).Google Scholar
• 301  Center for Disease Control Public Health Image Library http://phil.cdc.govGoogle Scholar
• 302  Wikimedia.org http://commons.wikimedia.org/wiki/file:entamoeba_histolytica_life_cycle-en.svgGoogle Scholar