Chemotherapeutic options for the treatment of human trichomoniasis

Küng, Erik; Fürnkranz, Ursula; Walochnik, Julia

doi:10.1016/j.ijantimicag.2018.10.016

Cited by 21 publications

(7 citation statements)

References 176 publications

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“…They concluded that improved clinical diseases to prevent infection ascending would prevent the persistent burden of infertility. Küng et al (2019) in Austria reported that T. vaginalis, the causative agent of the commonest sexually transmitted disease worldwide, was associated with severe complications, including the infertility, preterm labor, cancer and increasing risk of HIV transmission.…”

Section: Discussionmentioning

confidence: 99%

Potential Role of Trichomonas Vaginalis in Women With Primary and Secondary Infertility in Beni-Suef, Egypt

Ibrahim¹,

Ismail²,

Elaskary³

et al. 2021

Journal of the Egyptian Society of Parasitology

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Section: Discussionmentioning

confidence: 99%

Potential Role of Trichomonas Vaginalis in Women With Primary and Secondary Infertility in Beni-Suef, Egypt

Ibrahim¹,

Ismail²,

Elaskary³

et al. 2021

Journal of the Egyptian Society of Parasitology

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“…The trichomonacidal activity of proteasome inhibitors was not impacted by resistance to the most commonly used drug for treating trichomoniasis, metronidazole. This suggests that proteasome inhibition holds promise as a rescue therapy for infections refractory to nitro drugs (11,53). Nitro drugs act in a two-step sequence, involving initial activation by reduction to reactive intermediates, followed by covalent binding of intermediates to and inactivation of multiple target molecules.…”

Section: Discussionmentioning

confidence: 99%

20S Proteasome as a Drug Target in Trichomonas vaginalis

O’Donoghue

Bibo-Verdugo

Miyamoto

et al. 2019

Antimicrob Agents Chemother

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Trichomoniasis is a sexually transmitted disease with hundreds of millions of annual cases worldwide. Approved treatment options are limited to two related nitro-heterocyclic compounds, yet resistance to these drugs is an increasing concern. New antimicrobials against the causative agent, Trichomonas vaginalis, are urgently needed. We show here that clinically approved anticancer drugs that inhibit the proteasome, a large protease complex with a critical role in degrading intracellular proteins in eukaryotes, have submicromolar activity against the parasite in vitro and on-target activity against the enriched T. vaginalis proteasome in cell-free assays. Proteomic analysis confirmed that the parasite has all seven α and seven β subunits of the eukaryotic proteasome although they have only modest sequence identities, ranging from 28 to 52%, relative to the respective human proteasome subunits. A screen of proteasome inhibitors derived from a marine natural product, carmaphycin, revealed one derivative, carmaphycin-17, with greater activity against T. vaginalis than the reference drug metronidazole, the ability to overcome metronidazole resistance, and reduced human cytotoxicity compared to that of the anticancer proteasome inhibitors. The increased selectivity of carmaphycin-17 for T. vaginalis was related to its >5-fold greater potency against the β1 and β5 catalytic subunits of the T. vaginalis proteasome than against the human proteasome subunits. In a murine model of vaginal trichomonad infection, proteasome inhibitors eliminated or significantly reduced parasite burden upon topical treatment without any apparent adverse effects. Together, these findings validate the proteasome of T. vaginalis as a therapeutic target for development of a novel class of trichomonacidal agents.

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“…This release of viral dsRNA may be favoured by the presence of wide channels in the virion [ 45 ]. Although the percentage of clinical T. vaginalis isolates resistant to 5-nitroimidazole treatment is increasing [ 57 ], and although a correlation with the presence of TVV has been postulated, this is still debated and poorly understood [ 53 , 58 , 59 ]. Paradoxically, in the case of infection caused by T. vaginalis carrying TVV, failure of anti-protozoan therapy with metronidazole in order to prevent preterm delivery in pregnant women results in an exacerbated inflammatory response explained by the increased release of virions and dsRNA as a result of parasite killing [ 45 , 60 ].…”

Section: Main Textmentioning

confidence: 99%

Viruses of protozoan parasites and viral therapy: Is the time now right?

Barrow

Dujardin

Fasel

et al. 2020

Virol J

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Infections caused by protozoan parasites burden the world with huge costs in terms of human and animal health. Most parasitic diseases caused by protozoans are neglected, particularly those associated with poverty and tropical countries, but the paucity of drug treatments and vaccines combined with increasing problems of drug resistance are becoming major concerns for their control and eradication. In this climate, the discovery/repurposing of new drugs and increasing effort in vaccine development should be supplemented with an exploration of new alternative/synergic treatment strategies. Viruses, either native or engineered, have been employed successfully as highly effective and selective therapeutic approaches to treat cancer (oncolytic viruses) and antibiotic-resistant bacterial diseases (phage therapy). Increasing evidence is accumulating that many protozoan, but also helminth, parasites harbour a range of different classes of viruses that are mostly absent from humans. Although some of these viruses appear to have no effect on their parasite hosts, others either have a clear direct negative impact on the parasite or may, in fact, contribute to the virulence of parasites for humans. This review will focus mainly on the viruses identified in protozoan parasites that are of medical importance. Inspired and informed by the experience gained from the application of oncolytic virus- and phage-therapy, rationally-driven strategies to employ these viruses successfully against parasitic diseases will be presented and discussed in the light of the current knowledge of the virus biology and the complex interplay between the viruses, the parasite hosts and the human host. We also highlight knowledge gaps that should be addressed to advance the potential of virotherapy against parasitic diseases.

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Chemotherapeutic options for the treatment of human trichomoniasis

Cited by 21 publications

References 176 publications

Potential Role of Trichomonas Vaginalis in Women With Primary and Secondary Infertility in Beni-Suef, Egypt

Potential Role of Trichomonas Vaginalis in Women With Primary and Secondary Infertility in Beni-Suef, Egypt

20S Proteasome as a Drug Target in Trichomonas vaginalis

Viruses of protozoan parasites and viral therapy: Is the time now right?

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