Development of Drug Resistance in Trichomonas vaginalis and its Overcoming with Natural Products

Gehrig, Stefanie; Efferth, Thomas

doi:10.2174/1874847300902010021

Cited by 18 publications

(12 citation statements)

References 69 publications

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“…It mostly affects women and to minor degree men; about 170 million people are infected worldwide. It is often associated with HIV and cervical cancer [ 54 ]. Standard chemotherapy includes 5-nitroimidazoles, such as metronidazole and tinidazole.…”

Section: Antiparasitic Medicinal Plants and Their Secondary Metabomentioning

confidence: 99%

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Medicinal Plants: A Source of Anti-Parasitic Secondary Metabolites

2012

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This review summarizes human infections caused by endoparasites, including protozoa, nematodes, trematodes, and cestodes, which affect more than 30% of the human population, and medicinal plants of potential use in their treatment. Because vaccinations do not work in most instances and the parasites have sometimes become resistant to the available synthetic therapeutics, it is important to search for alternative sources of anti-parasitic drugs. Plants produce a high diversity of secondary metabolites with interesting biological activities, such as cytotoxic, anti-parasitic and anti-microbial properties. These drugs often interfere with central targets in parasites, such as DNA (intercalation, alkylation), membrane integrity, microtubules and neuronal signal transduction. Plant extracts and isolated secondary metabolites which can inhibit protozoan parasites, such as Plasmodium, Trypanosoma, Leishmania, Trichomonas and intestinal worms are discussed. The identified plants and compounds offer a chance to develop new drugs against parasitic diseases. Most of them need to be tested in more detail, especially in animal models and if successful, in clinical trials.

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Section: Antiparasitic Medicinal Plants and Their Secondary Metabomentioning

confidence: 99%

“…Because some of the Trichomonas strains have become resistant to the standard drugs, new chemicals are needed. Natural products have been analysed as an alternative and several alkaloids (e.g., berberine), dibenzofurans, anthraquinones, polyacetylenes, saponins, and diterpenes [ 54 ].…”

Section: Antiparasitic Medicinal Plants and Their Secondary Metabomentioning

confidence: 99%

Medicinal Plants: A Source of Anti-Parasitic Secondary Metabolites

2012

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“…( Tamaoki et al, 1986 ). This screening data contributes to increasing evidence driving renewed interest in microbial natural products as anti-trichomonals ( Gehrig and Efferth, 2009 ; King et al, 2019 ), as well as potential mechanisms and scaffolds that could be targeted for further exploration, identifying pivotal sites of action in eukaryotes that are fundamental to modern anti-tumour discovery.…”

Section: Introductionmentioning

confidence: 84%

TriTOX: A novel Trichomonas vaginalis assay platform for high-throughput screening of compound libraries

Lam

Vuong²,

Jex

et al. 2021

International Journal for Parasitology: Drugs and Drug Resistan

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Trichomonas vaginalis is a neglected urogenital parasitic protist that causes 170 million cases of trichomoniasis annually, making it the most prevalent non-viral, sexually transmitted disease. Trichomoniasis treatment relies on nitroheterocyclics, such as metronidazole. However, with increasing drug-resistance, there is an urgent need for novel anti-trichomonals. Little progress has been made to translate anti-trichomonal research into commercialised therapeutics, and the absence of a standardised compound-screening platform is the immediate stumbling block for drug-discovery. Herein, we describe a simple, cost-effective growth assay for T. vaginalis and the related Tritrichomonas foetus . Tracking changes in pH were a valid indicator of trichomonad growth ( T. vaginalis and T. foetus ), allowing development of a miniaturised, chromogenic growth assay based on the phenol red indicator in 96- and 384-well microtiter plate formats. The outputs of this assay can be quantitatively and qualitatively assessed, with consistent dynamic ranges based on Z′ values of 0.741 and 0.870 across medium- and high-throughput formats, respectively. We applied this high-throughput format within the largest pure-compound microbial metabolite screen (812 compounds) for T. vaginalis and identified 43 hit compounds. We compared these identified compounds to mammalian cell lines, and highlighted extensive overlaps between anti-trichomonal and anti-tumour activity. Lastly, observing nanomolar inhibition of T. vaginalis by fumagillin, and noting this compound has reported activity in other protists, we performed in silico analyses of the interaction of fumagillin with its molecular target methionine aminopeptidase 2 for T. vaginalis , Giardia lamblia and Entamoeba histolytica , highlighting potential for fumagillin as a broad-spectrum anti-protistal against microaerophilic protists. Together, this new platform will accelerate drug-discovery efforts, underpin drug-resistance screening in trichomonads, and contributing to a growing body of evidence highlighting the potential of microbial natural products as novel anti-protistals.

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“…On the other side, there is mounting evidence that medicinal plants with their panoply of secondary metabolites reveal considerable activity against parasites causing neglected diseases [50][51][52][53][54][55][56][57][58][59][60][61]. This paradox illustrates the need for systematic research to improve and utilize the full potential of medicinal herbs.…”

Section: Future Perspectivesmentioning

confidence: 99%