Concept: Trichomonas vaginalis
The microaerophilic parasite Trichomonas vaginalis is a causative agent of painful vaginitis or urethritis, termed trichomoniasis, and can also cause preterm delivery or stillbirth. Treatment of trichomoniasis is almost exclusively based on the nitroimidazole drugs metronidazole and tinidazole. Metronidazole resistance in T. vaginalis does occur and is often associated with treatment failure. In most cases, metronidazole-resistant isolates remain susceptible to tinidazole, but cross resistance between the two closely related drugs can be a problem. In this study we measured activities of thioredoxin reductase and flavin reductase in four metronidazole-susceptible and five metronidazole-resistant isolates. These enzyme activities had been previously found to be downregulated in T. vaginalis with high-level metronidazole resistance induced in the laboratory. Further, we aimed at identifying factors causing metronidazole resistance and compared the protein expression profiles of all nine isolates by application of two-dimensional gel electrophoresis (2DE). Thioredoxin reductase activity was nearly equal in all strains assayed but flavin reductase activity was clearly down-regulated, or even absent, in metronidazole-resistant strains. Since flavin reductase has been shown to reduce oxygen to hydrogen peroxide, its down-regulation could significantly contribute to the impairment of oxygen scavenging as reported by others for metronidazole-resistant strains. Analysis by 2DE revealed down-regulation of alcohol dehydrogenase 1 (ADH1) in strains with reduced sensitivity to metronidazole, an enzyme that could be involved in detoxification of intracellular acetaldehyde.
OBJECTIVE: To discuss the epidemiology of Trichomonas vaginalis (TV) and HIV co-infections, the role of TV in acquisition and transmission of HIV, special treatment considerations for TV among women with HIV and the prevention of TV among HIV-infected persons. DESIGN: Systematic review. DATA SOURCE: Review of literature of EMBASE and PubMed databases from January 1990 to February 2013. Search keywords included TV, HIV co-infections, HIV acquisition, HIV transmission, HIV shedding, TV treatment, HIV and couples studies. REVIEW METHOD: We included studies of any design that contained the selected search words and were published during the specified time frame. We then searched the reference lists of included papers for additional papers and included these when relevant. RESULTS: There is strong evidence that TV increases both transmission and acquisition of HIV among women, and that successful treatment for TV can reduce HIV genital shedding. Single dose metronidazole (MTZ) should no longer be used for HIV+ women with TV given the high rates of asymptomatic bacterial vaginosis co-infections and other factors that may render MTZ less effective in HIV+ women. Prevention of TV among HIV+ persons is similar to among HIV, including promotion of condoms as well as regular screening and prompt treatment. There may be a role for expedited partner treatment for the prevention of repeat infections, but most repeat infections are clinical treatment failures. Diligence in screening and treating TV among both HIV- susceptible and HIV+ persons is an important public health strategy.
This review focused on potential regulatory mechanisms of Trichomonas vaginalis virulence properties, cytoadherence, cytotoxicity, phagocytosis, hemolysis, induction of apoptosis, and immune evasion in response to environmental factors of the human urogenital tract, iron, zinc, and polyamines. Understanding the multifactorial nature of trichomonal pathogenesis and its regulation may help to unravel the survival strategies of trichomonads and to implement prevention policies, opportune diagnosis, and alternative treatments for control of trichomoniasis.
Trichomonas vaginalis is the causative agent of trichomonosis, the most common non-viral sexually transmitted disease. Infection with this protozoan may have serious consequences, especially for women. Currently, 5-nitroimidazole drugs are the treatment of choice for trichomonosis, but the emergence of resistance has limited the effectiveness of this therapy. In this context, this study aimed to evaluate the anti-T. vaginalis activity of marine-associated fungi found in the South Brazilian Coast. A total of 42 marine-associated fungal species (126 filtrate samples) isolated from 39 different marine organisms, mainly sponges, were selected to be screened against T. vaginalis. Of these, two filtrate samples from Hypocrea lixii F02 and Penicillium citrinum F40 showed significant growth-inhibitory activity (up to 100%) against ATCC 30236 and fresh clinical isolates, including a metronidazole-resistant isolate. Minimum inhibitory concentration (MIC) values of H. lixii F02 and P. citrinum F40 samples for all isolates tested, including the metronidazole-resistant isolate, were 2.5 mg/mL. The kinetic growth curve showed that the filtrate samples were able to reduce the density of parasites to zero within 24 hours of incubation, which was confirmed by microscopy. Both fungal filtrate samples exhibited no hemolytic activity, and the P. citrinum F40 filtrate sample showed low cytotoxicity against Vero cells. These data suggest that marine-associated fungi from the South Brazilian Coast may produce potential candidates for further investigation and possible use in the treatment of metronidazole-resistant trichomonosis.
Recent literature has reported increased accuracy of Trichomonas vaginalis transcription-mediated amplification (TMA)-based analyte-specific reagent (ASR) testing in female populations. A retrospective investigation assessed 7,277 female first-void urine, cervical, or vaginal specimens submitted from a high-prevalence sexually transmitted infection (STI) community to characterize prevalence of disease etiologies. The most common STI phenotype reflected detection of solely T. vaginalis (54.2% of all health care encounters that resulted in STI detection). In females with detectable T. vaginalis, codetection of Chlamydia trachomatis and Neisseria gonorrhoeae occurred in 7.8% and 2.7% of health care encounters, respectively. The mean age of women with detectable T. vaginalis (30.6) was significantly higher than those for women with C. trachomatis or N. gonorrhoeae (22.3 and 21.6, respectively; P < 0.0001). T. vaginalis was the predominant sexually transmitted agent in women over the age of 20 (P < 0.0002). C. trachomatis was the most commonly detected agent in females under the age of 21, particularly from cervical specimens. However, first-void urine detection rates for T. vaginalis and C. trachomatis within this age demographic demonstrated no difference (P = 0.92). While overall and cervical specimen-derived detection of T. vaginalis within African American majority geographical locales outweighed that within majority Caucasian geographical regions (P ≤ 0.004), this difference was not noted with first-void urine screening (P = 0.54). Health care professionals can consider TMA-based T. vaginalis screening for a wide age range of patients; incorporation of first-void urine specimens into screening algorithms can potentiate novel insight into the epidemiology of trichomoniasis.
Trichomonas has been reported to be rare in Australia’s major cities while remaining very common in some extremely remote Aboriginal communities. This study examined the Trichomonas prevalence and relationship to remoteness among patients attending sexual health clinics in rural and remote areas of New South Wales, Australia.
In this work, evidence for a critical role of Trichomonas vaginalis protein phosphatase 1 gamma (TvPP1γ) in proliferation and attachment of the parasite to the mammalian cell is provided. Firstly, proliferation and attachment of T. vaginalis parasites to HeLa cells was blocked by calyculin A (CA), a potent PP1 inhibitor. Secondly, it was demonstrated that the enzyme activity of native and recombinant TvPP1γ proteins was inhibited by CA. Thirdly, reverse genetic studies confirmed that antisense oligonucleotides targeted to PP1γ but not PP1α or β inhibited proliferation and attachment of trichomonads CA-treated parasites underwent cytoskeletal modifications, including a lack of axostyle typical labelling, suggesting that cytoskeletal phosphorylation could be regulated by a CA-sensitive phosphatase where the role of PP1γ could not be ruled out. Analysis of subcellular distribution of TvPP1γ by cell fractionation and electron microscopy demonstrated the association between TvPP1γ and the cytoskeleton. The expression of adhesins, AP120 and AP65, at the cell surface was also inhibited by CA. The concomitant inhibition of expression of adhesins and changes in the cytoskeleton in CA-treated parasites suggest a specific role for PP1γ -dependent dephosphorylation in the early stages of the host-parasite interaction. Molecular modelling of TvPP1γ showed the conservation of residues critical for maintaining proper folding into the gross structure common to PP1 proteins. Taken together, these results suggest that TvPP1γ could be considered a potential novel drug target for treatment of trichomoniasis.
Trichomonas vaginalis infections are usually asymptomatic or can result in non-specific clinical symptoms, which makes laboratory-based detection of this protozoan parasite essential for diagnosis and treatment. We report the development of a battery of highly sensitive and specific PCR assays for detection of T. vaginalis in urine, a non-invasive specimen, and development of a protocol for differentiating among Trichomonas species that commonly infect humans.
Comparative Inhibition Study of Compounds Identified in the Methanolic Extract of Apamarga Kshara Against Trichomonas vaginalis Carbamate Kinase (TvCK): An Enzoinformatics Approach
- Interdisciplinary sciences, computational life sciences
- Published over 3 years ago
In the present study, we have identified ten compounds, namely dodecanol acid, myristic acid, neophytadiene, palmitic acid, heptadecanoic acid, linoleic acid, elaidic acid, 3-7-dimethyl acid, stearic acid and methyl eicos acid, of the methanolic extract of Apamarga Kshara by GC-MS analysis. Apamarga Kshara has been reported to be active against cervical erosion. Major causal organism for cervical erosion is Trichomonas vaginalis. However, there is a paucity of information about the mechanism of action and inhibitory effect of the biologically active natural compounds presented in A. Kshara against this organism (T. vaginalis). Therefore, present investigation was conducted to observe possible interactions of these compounds on T. vaginalis carbamate kinase using molecular docking software ‘AutoDock 4.2.’ Identification of the amino acid residues crucial for the interaction between T. vaginalis carbamate kinase and these natural compounds is of due scientific interest. The study will aid in efficacious and safe clinical use of the above-mentioned compounds.
The flagellated protozoan parasite Trichomonas vaginalis is the etiologic agent of trichomoniasis, the most common non-viral sexually transmitted infection worldwide. As an obligate extracellular pathogen, adherence to epithelial cells is critical for parasite survival within the human host and a better understanding of this process is a prerequisite for the development of therapies to combat infection. In this sense, recent work has shown S-acylation as a key modification that regulates pathogenesis in different protozoan parasites. However, there are no reports indicating whether this post-translational modification is a mechanism operating in T. vaginalis. In order to study the extent and function of S-acylation in T. vaginalis biology, we undertook a proteomic study to profile the full scope of S-acylated proteins in this parasite and reported the identification of 363 proteins involved in a variety of biological processes such as protein transport, pathogenesis related and signaling, among others. Importantly, treatment of parasites with the palmitoylation inhibitor 2-bromopalmitate causes a significant decrease in parasite: parasite aggregation as well as adherence to host cells suggesting that palmitoylation could be modifying proteins that are key regulators of Trichomonas vaginalis pathogenesis.