Reduction of niridazole by metronidazole resistant and susceptible strains of <i>Trichomonas vaginalis</i>

Rowlands, Christopher C.; Yarlett, Nigel; Evans, J. C.; Lloyd, David

doi:10.1017/s0031182000053488

Cited by 10 publications

(4 citation statements)

References 20 publications

(15 reference statements)

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“…In contrast, nimorazole, a nitrothiazole derivative, is converted into two major metabolites that possess significantly higher trichomonicidal activity than metronidazole (177). Nimorazole was active against both metronidazolesensitive and -resistant T. vaginalis strains (334,335).…”

Section: Current Chemotherapeutics For T Vaginalis Infectionmentioning

confidence: 99%

Current Therapeutics, Their Problems, and Sulfur-Containing-Amino-Acid Metabolism as a Novel Target against Infections by “Amitochondriate” Protozoan Parasites

2007

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SUMMARY The “amitochondriate” protozoan parasites of humans Entamoeba histolytica, Giardia intestinalis, and Trichomonas vaginalis share many biochemical features, e.g., energy and amino acid metabolism, a spectrum of drugs for their treatment, and the occurrence of drug resistance. These parasites possess metabolic pathways that are divergent from those of their mammalian hosts and are often considered to be good targets for drug development. Sulfur-containing-amino-acid metabolism represents one such divergent metabolic pathway, namely, the cysteine biosynthetic pathway and methionine γ-lyase-mediated catabolism of sulfur-containing amino acids, which are present in T. vaginalis and E. histolytica but absent in G. intestinalis. These pathways are potentially exploitable for development of drugs against amoebiasis and trichomoniasis. For instance, l-trifluoromethionine, which is catalyzed by methionine γ-lyase and produces a toxic product, is effective against T. vaginalis and E. histolytica parasites in vitro and in vivo and may represent a good lead compound. In this review, we summarize the biology of these microaerophilic parasites, their clinical manifestation and epidemiology of disease, chemotherapeutics, the modes of action of representative drugs, and problems related to these drugs, including drug resistance. We further discuss our approach to exploit unique sulfur-containing-amino-acid metabolism, focusing on development of drugs against E. histolytica.

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Section: Current Chemotherapeutics For T Vaginalis Infectionmentioning

confidence: 99%

Current Therapeutics, Their Problems, and Sulfur-Containing-Amino-Acid Metabolism as a Novel Target against Infections by “Amitochondriate” Protozoan Parasites

2007

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“…Both metronidazole-sensitive and -resistant strains are inhibited by this drug. Chemical analyses have shown that niridazole may have multiple modes of action, accounting for its wide range of inhibitory effects, but specific mechanisms are unknown (129).…”

Section: Other Chemotherapeutic Agentsmentioning

confidence: 99%

Treatment of Infections Caused by Metronidazole-ResistantTrichomonas vaginalis

et al. 2004

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Infections with the sexually transmitted protozoan Trichomonas vaginalis are usually treated with metronidazole, a 5-nitroimidazole drug derived from the antibiotic azomycin. Metronidazole treatment is generally efficient in eliminating T. vaginalis infection and has a low risk of serious side effects. However, studies have shown that at least 5% of clinical cases of trichomoniasis are caused by parasites resistant to the drug. The lack of approved alternative therapies for T. vaginalis treatment means that higher and sometimes toxic doses of metronidazole are the only option for patients with resistant disease. Clearly, studies of the treatment and prevention of refractory trichomoniasis are essential. This review describes the mechanisms of metronidazole resistance in T. vaginalis and provides a summary of trichomonicidal and vaccine candidate drugs

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“…34,35 For the details of metronidazole activation by PFO and ferredoxin, the reader is referred to studies described by Moreno and colleagues 36,37 and Yarlett and colleagues. [38][39][40] Early work on metronidazole resistance in Trichomonas vaginalis using resistant clinical isolate CDC085 and susceptible laboratory strain ATCC30001 suggested two possible hypotheses for resistance: (1) that a defective ferredoxin protein existed in the resistant isolate; or (2) reduced levels of the ferredoxin protein were present in CDC085. 39 With the cloning of the T. vaginalis ferredoxin gene, 41 a detailed molecular analysis of the ferredoxin gene and its expression in sensitive and resistant cells was carried out.…”

Section: Trichomonas Vaginalis and Tritrichomonas Foetusmentioning

confidence: 99%