Repurposing the open access malaria box reveals compounds with activity against Tritrichomonas foetus trophozoites

Martin, Katy A.; Chelladurai, Jeba Jesudoss; Bader, Christopher D.; Carreiro, Elizabeth; Long, Katelyn; Thompson, Kylie; Brewer, Matthew T.

doi:10.1016/j.ijpddr.2020.06.003

Cited by 7 publications

(8 citation statements)

References 21 publications

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“…There are currently no labeled treatments for trichomoniasis in cattle. 10 As previously discussed, cows typically will clear the infection after a period of infertility, with a few remaining as carriers in the herd. There has been some work looking into novel uses of compounds that have previously been shown to have efficacy against the protozoan that causes malaria (Plasmodium falciparum).…”

Section: Potential Opportunities For Treatmentsmentioning

confidence: 97%

“…1 There are currently no approved methods to treat trichomoniasis in the bovine male. 10 Young bulls are more resistant to infection than are older bulls, which is an important feature in control and eradication programs. 6 Regions in which trichomoniasis remains a challenge are those in which natural service is the predominant means of breeding, and in those regions in which there is a significant amount of comingling of herds for grazing purposes.…”

Section: Persistence In Beef Cattlementioning

confidence: 99%

“…There has been some work looking into novel uses of compounds that have previously been shown to have efficacy against the protozoan that causes malaria (Plasmodium falciparum). 10 In this work, there were 4 compounds identified that had lethal activity against T. foetus in vitro, one of which was nearly identical in chemical structure to a compound that has historically been used in human medicine, and currently has application of use as a mold inhibitor in feeds. More work needs to be done in this research area before a viable treatment option is developed, but these results are promising.…”

Section: Potential Opportunities For Treatmentsmentioning

confidence: 99%

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Bovine trichomoniasis overview and testing

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2023

AABP Proceedings

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Bovine trichomoniasis, caused by Tritrichomonas foetus, is a venereal disease of cattle, resulting in infertility, pregnancy losses, abortion and delayed calving seasons. The disease has global distribution, with greater prevalence in areas in which natural service is the primary means of reproduction. When artificial insemination, with appropriate hygiene practices, is implemented, as well as aggressive testing and culling of positive bulls, control and eradication of the disease is possible. Additionally, minimizing co-mingling of animals with unknown status through herd additions or on public grazing lands will help decrease the likelihood of introduction into negative herds, and contribute significantly to the decrease in prevalence in the local region. Testing methods have improved over the last 100 years; however, proper sample collection and handling are still paramount to gaining true positive results in infected bulls.

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Section: Potential Opportunities For Treatmentsmentioning

confidence: 97%

Section: Persistence In Beef Cattlementioning

confidence: 99%

Section: Potential Opportunities For Treatmentsmentioning

confidence: 99%

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Bovine trichomoniasis overview and testing

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2023

AABP Proceedings

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“…TRITRICHOMONAS foetus (T. foetus) is a unicellular flagellated parasite that primarily inhabits the reproductive (genitourinary) tissues of livestock, causing bovine trichomoniasis, a venereal infection. This parasite has a single nucleus and lacks mitochondria, instead possessing a spherical hydrogenosome that regulates its metabolism (Dąbrowska et al, 2019;Martin et al, 2020). Bovine trichomoniasis has a significant economic impact on the livestock sector due to extended calving intervals, suboptimal weights for commercialization, and increased feeding costs to reach the ideal market weight (Rae & Crews, 2006).…”

Section: Introductionmentioning

confidence: 99%

Exposure of Tritrichomonas foetus to sublethal doses of metronidazole induces a specific proinflammatory response in murine macrophages

Ceballos‐Góngora,

Torres‐Romero,

Arana‐Argáez

et al. 2023

J Eukaryotic Microbiology

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Tritrichomonas foetus is a flagellated parasite that primarily infects the reproductive tissues of livestock, causing bovine trichomoniasis. The cytoplasmic membrane of T. foetus contains various compounds that contribute to adherence, colonization, and pathogenicity. Metronidazole (MTZ) is the main treatment for trichomoniasis, but the emergence of drug‐resistant strains is a concern due to improper use and dosing. T. foetus infection induces inflammation, and macrophages are key players in the immune response. However, our understanding of the host's immune response to T. foetus is limited, and the specific mechanisms underlying these responses are not well understood. This study aimed to investigate the impact of T. foetus surface proteins from trophozoites cultured under different sublethal MTZ conditions (MTZ‐treated T. foetus MPs) on macrophage activation. By analyzing cytokine levels and gene expression in murine macrophages, we demonstrated that MTZ‐treated T. foetus MPs induce a specific proinflammatory response. MTZ‐treated T. foetus MPs‐exposed macrophages exhibited a higher NO and H2O2 production and overexpression of iNOS and NOX‐2 genes in comparison to untreated T. foetus. Additionally, MTZ‐treated T. foetus MPs triggered a significant induction of the proinflammatory cytokines IL‐1β, IL‐6, TNF‐α, and IFN‐γ, as well as the overexpression of the TLR4, MyD88, and NF‐κB genes on murine macrophages. The study aimed to unravel the immunological response and potential proinflammatory pathways involved in T. foetus infection and MTZ stress. Understanding the immune responses and mechanisms through which T. foetus surface proteins activate macrophages can contribute to the development of new therapeutic strategies for controlling bovine trichomoniasis.

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“…Infected bulls are typically without clinical signs while cows experience metritis and early embryonic death ( 1 , 2 ). There are currently no drugs approved for the treatment of T. foetus in the United States ( 3 , 4 ). Although most cows ultimately clear the infection, lost pregnancies lead to a prolonged calving period and an increase in open cows ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

Bovine Trichomonosis Cases in the United States 2015–2019

2021

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Tritrichomonas foetus is a sexually-transmitted protozoan parasite that causes early embryonic death in cattle. Tritrichomonas foetus is enzootic in the United States but is not a reportable disease at the national level. Thus, it is difficult to understand the prevalence and relative distribution of the disease for the purpose of developing appropriate control measures. In this study, a survey of state veterinarians was used to determine the number of reported cases in each state from 2015 to 2019. Our investigation revealed infections in 25 different states and a total of 3,817 reported cases nationwide. Infections occurred throughout different regions of the country, and numbers of cases were only weakly correlated with total number of cattle in each state. Tritrichomonas foetus is a significant pathogen in the United States and understanding the relative distribution of the parasite is useful for prioritizing surveillance and intervention strategies going forward.

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Repurposing the open access malaria box reveals compounds with activity against Tritrichomonas foetus trophozoites

Cited by 7 publications

References 21 publications

Bovine trichomoniasis overview and testing

Bovine trichomoniasis overview and testing

Exposure of Tritrichomonas foetus to sublethal doses of metronidazole induces a specific proinflammatory response in murine macrophages

Bovine Trichomonosis Cases in the United States 2015–2019

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