The Role of Purinergic Signaling in Trichomonas vaginalis Infection

2020 ◽  
Vol 20 ◽  
Author(s):  
Micheli Ferla ◽  
Tiana Tasca
Keyword(s):  
Drug Targets ◽  
Trichomonas Vaginalis ◽  
Hiv Transmission ◽  
Cell Damage ◽  
Purinergic Signaling ◽  
Host Cells ◽  
Purine Nucleotides ◽  
Cellular Effects ◽  
Adverse Pregnancy ◽  
Purine Salvage Pathways

: Trichomoniasis, one of the most common non-viral sexually transmitted infections worldwide, is caused by the parasite Trichomonas vaginalis. The pathogen colonizes the human urogenital tract and the infection is associated with complications such as adverse pregnancy outcomes, cervical cancer, and an increase in HIV transmission. The mecha-nisms of pathogenicity are multifactorial, and controlling immune responses is essential for infection maintenance. Extra-cellular purine nucleotides are released by cells in physiological and pathological conditions, and they are hydrolyzed by enzymes called ecto-nucleotidases. The cellular effects of nucleotides and nucleosides occur via binding to purinoceptors, or throughthe uptake by nucleoside transporters. Altogether, enzymes, receptors and transporters constitute the purinergic signaling, a cellular network that regulates several effects in practically all systems including mammals, helminths, proto-zoa, bacteria, and fungi. In this context, this review updates the data on purinergic signaling involved in T. vaginalis biol-ogy and interaction with host cells, focusing on the characterization of ecto-nucleotidases and on purine salvage pathways. The implications of the final products, the nucleosides adenosine and guanosine, for human neutrophil response and vagi-nal epithelial cell damage reveal the purinergic signaling as a potential new mechanism for alternative drug targets.

scholarly journals Trichomonas vaginalis: current understanding of host–parasite interactions

2011 ◽  
Vol 51 ◽  
pp. 161-175 ◽  
Author(s):  
Christopher M. Ryan ◽  
Natalia de Miguel ◽  
Patricia J. Johnson
Keyword(s):  
Drug Targets ◽  
Trichomonas Vaginalis ◽  
Molecular Data ◽  
Host Cells ◽  
Current Status ◽  
Rational Approach ◽  
Sexually Transmitted ◽  
Host Parasite Interactions ◽  
Future Challenges ◽  
Host Parasite

Trichomonas vaginalis is a sexually transmitted obligate extracellular parasite that colonizes the human urogenital tract. Despite being of critical importance to the parasite's survival relatively little is known about the mechanisms employed by T. vaginalis to establish an infection and thrive within its host. Several studies have focused on the interaction of the parasite with host cells and extracellular matrix, identifying multiple suspected T. vaginalis adhesins. However, with the exception of its surface lipophosphoglycan, the evidence supporting a role in adhesion is indirect or controversial for many candidate molecules. The availability of the T. vaginalis genome sequence paved the way for genomic analyses to search for proteins possibly involved in host–parasite interactions. Several proteomic analyses have also provided insight into surface, soluble and secreted proteins that may be involved in Trichomonas pathogenesis. Although the accumulation of molecular data allows for a more rational approach towards identifying drug targets and vaccine candidates for this medically important parasite, a continued effort is required to advance our understanding of its biology. In the present chapter, we review the current status of research aimed at understanding T. vaginalis pathogenesis. Applied experimental approaches, an overview of significant conclusions drawn from this research and future challenges are discussed.

The prevalence of Trichomonas vaginalis and Candida albicans infection in the lower genital tracts of antenatal patients in Abakaliki, Southeastern Nigeria

1970 ◽  
Vol 4 (1) ◽  
pp. 11-14 ◽  
Author(s):  
IM Sunday-Adeoye ◽  
JOK Adeoye ◽  
OUJ Umeora ◽  
PI Okonta
Keyword(s):  
Candida Albicans ◽  
Pregnancy Outcomes ◽  
Trichomonas Vaginalis ◽  
Dropout Rate ◽  
Antenatal Clinic ◽  
Southeastern Nigeria ◽  
High Dropout Rate ◽  
Adverse Pregnancy ◽  
June July ◽  
A Prospective Study

Aims: To determine the prevalence of Trichomonas vaginalis and Candida albican infection among anasymptomatic pregnant population and to document their pregnancy outcomes.Methods: This was a prospective study involving antenatal clinic attendees at the Ebonyi State UniversityTeaching Hospital, Abakaliki, Nigeria. They were randomly recruited and informed consent obtained. Vaginalspecimens were collected from them and analyzed in the laboratory. They were followed up till delivery andpregnancy outcomes documented.Results: Two hundred expectant mothers were recruited. The prevalence rate of Trichomonas vaginalis andCandida albicans were 0.5% and 27.5% respectively. Due to the high dropout rate in the study, it wasimpossible to make any reasonable inference about the pregnancy outcomes associated with these conditions.Conclusion: There is probably the need for the use of more sophisticated methods for the detection ofTrichomonas vaginalis. The existing methods in most laboratories in the country may not be adequate. Thereis also probably the need for a larger sample size and a stricter follow up of the patients in order to documentany adverse pregnancy outcomes associated with these conditions.Keywords: Prevalence; Trichomonas vaginalis; Candida albicans; antenatal careDOI: 10.3126/njog.v4i1.3325Nepal Journal of Obstetrics and Gynaecology June-July 2009; 4(1): 11-14

scholarly journals RNA-Dependent RNA Polymerase as a Target for COVID-19 Drug Discovery

2020 ◽  
Vol 25 (10) ◽  
pp. 1141-1151 ◽  
Author(s):  
Wei Zhu ◽  
Catherine Z. Chen ◽  
Kirill Gorshkov ◽  
Miao Xu ◽  
Donald C. Lo ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
High Throughput Screening ◽  
Drug Targets ◽  
Host Cells ◽  
Host Proteins ◽  
Rna Dependent Rna Polymerase ◽  
Global Health Issue ◽  
Repurposed Drugs ◽  
Viral Enzyme ◽  
Target Effects

COVID-19 respiratory disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has rapidly become a global health issue since it emerged in December 2019. While great global efforts are underway to develop vaccines and to discover or repurpose therapeutic agents for this disease, as of this writing only the nucleoside drug remdesivir has been approved under Emergency Use Authorization to treat COVID-19. The RNA-dependent RNA polymerase (RdRP), a viral enzyme for viral RNA replication in host cells, is one of the most intriguing and promising drug targets for SARS-CoV-2 drug development. Because RdRP is a viral enzyme with no host cell homologs, selective SARS-CoV-2 RdRP inhibitors can be developed that have improved potency and fewer off-target effects against human host proteins and thus are safer and more effective therapeutics for treating COVID-19. This review focuses on biochemical enzyme and cell-based assays for RdRPs that could be used in high-throughput screening to discover new and repurposed drugs against SARS-CoV-2.

scholarly journals Trichomonas vaginalis Infection among Pregnant Women in Jimma University Specialized Hospital, Southwest Ethiopia

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Abdurehman Eshete ◽  
Zeleke Mekonnen ◽  
Ahmed Zeynudin
Keyword(s):  
Pregnant Women ◽  
Trichomonas Vaginalis ◽  
Cross Sectional Study ◽  
Culture Technique ◽  
Agar Culture ◽  
Cross Sectional ◽  
Sexually Transmitted ◽  
Specialized Hospital ◽  
Adverse Pregnancy ◽  
Jimma University

Background. Trichomonas vaginalis is a sexually transmitted parasitic protozoan known to be responsible for an estimated 180 million new infections per year, making it the most prevalent nonviral sexually transmitted pathogen worldwide. Method. A cross-sectional study design was conducted on vaginal swabs by wet mount and Modified Columbia Agar culture technique in Jimma University Specialized Hospital (JUSH), ANC clinic, Jimma, Ethiopia. The study was done to assess the magnitude and associated risk factors of T. vaginalis infection from December to May, 2011/2012. Result. A total of 361 pregnant women were involved in this study. From these, 18 (4.98%) of the pregnant women were positive for T. vaginalis infection by Modified Columbian Agar culture technique. Education status (AOR = 0.186, 95% CI: 0.059–0.585, P<0.05), patients with dysuria (AOR = 0.180; 95% CI: 0.046–0.704, P<0.05) and dyspareunia (AOR = 0.152; 95% CI: 0.035–0.667, P<0.05) were significantly associated with T. vaginalis infection. Conclusion. The prevalence of T. vaginalis infection at 4.89% is relatively high among young reproductive aged women. Because this infection increases the risk of HIV transmission and is associated with adverse pregnancy outcomes, there is a need for increased provision of health information concerning T. vaginalis to the community, educating women, screening, and treatment of T. vaginalis infection in Ethiopia.

scholarly journals BspA and Pmp proteins ofTrichomonas vaginalismediate adherence to host cells

2018 ◽  
Author(s):  
Maria R. Handrich ◽  
Sriram G. Garg ◽  
Ewen W. Sommerville ◽  
Robert P. Hirt ◽  
Sven B. Gould
Keyword(s):  
Trichomonas Vaginalis ◽  
Functional Characterization ◽  
Surface Proteins ◽  
Host Cells ◽  
Protein Families ◽  
Sexually Transmitted ◽  
Trace Back ◽  
Oral Pathogens ◽  
Adhesion Performance

AbstractTrichomonas vaginalisis one of the most widespread, sexually transmitted pathogens. The infection involves a morphological switch from a free-swimming pyriform trophozoite to an amoeboid cell upon adhesion to host epithelial cells. While details on how the switch is induced and to what proteins of the host surface the parasite adheres remain poorly characterized, several surface proteins of the parasite itself have been identified as potential candidates. Among those are two expanded protein families that harbor domains that share similarity to functionally investigated surface proteins of prokaryotic oral pathogens; these are the BspA proteins of Bacteroidales and Spirochaetales, and the Pmp proteins of Chlamydiales. We sequenced the transcriptomes of five Trichomonads and screened for the presence of BspA and Pmp domain-containing proteins and tested the ability of individualT. vaginaliscandidates to mediate adhesion. Here we demonstrate that (i) BspA and Pmp domain-containing proteins are specifically expanded inT. vaginalisin comparison to other Trichomonads, and that (ii) individual proteins of both families have the ability to increase adhesion performance in a non-virulentT. vaginalisstrain andTetratrichomonas gallinarum, a parasite usually known to infect birds but not humans. Our results initiate the functional characterization of these two broadly distributed protein families, whose origin we trace back to the origin of Trichomonads themselves.

scholarly journals Trichomonas vaginalis Lipophosphoglycan Mutants Have Reduced Adherence and Cytotoxicity to Human Ectocervical Cells

2005 ◽  
Vol 4 (11) ◽  
pp. 1951-1958 ◽  
Author(s):  
Felix D. Bastida-Corcuera ◽  
Cheryl Y. Okumura ◽  
Angie Colocoussi ◽  
Patricia J. Johnson
Keyword(s):  
Wheat Germ Agglutinin ◽  
Parent Strain ◽  
Trichomonas Vaginalis ◽  
Wheat Germ ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Host Cells ◽  
Chemical Mutagenesis ◽  
Reduced Adherence

ABSTRACT The extracellular human pathogen Trichomonas vaginalis is covered by a dense glycocalyx thought to play a role in host-parasite interactions. The main component of the glycocalyx is lipophosphoglycan (LPG), a polysaccharide anchored in the plasma membrane by inositol phosphoceramide. To study the role of LPG in trichomonads, we produced T. vaginalis LPG mutants by chemical mutagenesis and lectin selection and characterized them using morphological, biochemical, and functional assays. Two independently selected LPG mutants, with growth rates comparable to that of the wild-type (parent) strain, lost the ability to bind the lectins Ricinnus comunis agglutinin I (RCA120) and wheat germ agglutinin, indicating alterations in surface galactose and glucosamine residues. LPG isolated from mutants migrated faster than parent strain LPG on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, suggesting the mutants had shorter LPG molecules. Dionex high-performance anion exchange chromatography with pulsed amperometric detection analyses revealed galactosamine, glucosamine, galactose, glucose, mannose/xylose, and rhamnose as the main monosaccharides of T. vaginalis parent strain LPG. LPG from both mutants showed a reduction of galactose and glucosamine, corresponding with the reduced size of their LPG molecules and inability to bind the lectins RCA120 and wheat germ agglutinin. Mutant parasites were defective in attachment to plastic, a characteristic associated with avirulent strains of T. vaginalis. Moreover, the mutants were less adherent and less cytotoxic to human vaginal ectocervical cells in vitro than the parental strain. Finally, while parent strain LPG could inhibit the attachment of parent strain parasites to vaginal cells, LPG from either mutant could not inhibit attachment. These combined results demonstrate that T. vaginalis adherence to host cells is LPG mediated and that an altered LPG leads to reduced adherence and cytotoxicity of this parasite.

Glucose-restriction increasesTrichomonas vaginaliscellular damage towards HeLa cells and proteolytic activity of cysteine proteinases (CPs), such as TvCP2

Parasitology ◽  
2019 ◽  
Vol 146 (9) ◽  
pp. 1156-1166 ◽  
Author(s):  
Jesús F. T. Miranda-Ozuna ◽  
Luis Alberto Rivera-Rivas ◽  
Rosa Elena Cárdenas-Guerra ◽  
Mar Sarai Hernández-García ◽  
Sarahí Rodríguez-Cruz ◽  
...  
Keyword(s):  
Proteolytic Activity ◽  
Hela Cells ◽  
Trichomonas Vaginalis ◽  
Host Cells ◽  
Cellular Damage ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Cell Monolayers ◽  
Glucose Restriction ◽  
Effect Of Glucose

AbstractTrichomonas vaginalisinduces cellular damage to the host cells (cytotoxicity) through the proteolytic activity of multiple proteinases of the cysteine type (CPs). Some CPs are modulated by environmental factors such as iron, zinc, polyamines, etc. Thus, the goal of this study was to assess the effect of glucose onT. vaginaliscytotoxicity, proteolytic activity and the particular role of TvCP2 (TVAG_057000) during cellular damage. Cytotoxicity assays showed that glucose-restriction (GR) promotes the highest HeLa cell monolayers destruction (~95%) by trichomonads compared to those grown under high glucose (~44%) condition. Zymography and Western blot using different primary antibodies showed that GR increased the proteolytic activity, amount and secretion of certain CPs, including TvCP2. We further characterized the effect of glucose on TvCP2. TvCP2 increases in GR, localized in vesicles close to the plasma membrane and on the surface ofT. vaginalis. Furthermore, pretreatment of GR-trichomonads with an anti-TvCP2r polyclonal antibody specifically reduced the levels of cytotoxicity and apoptosis induction to HeLa cells in a concentration-dependent manner. In conclusion, our data show that GR, as a nutritional stress condition, promotes trichomonal cytotoxicity to the host cells, increases trichomonad proteolytic activity and amount of CPs, such as TvCP2 involved in cellular damage.

scholarly journals Adherence of Trichomonas vaginalis to SiHa Cells is Inhibited by Diphenyleneiodonium

2020 ◽  
Vol 8 (10) ◽  
pp. 1570
Author(s):  
Yeeun Kim ◽  
Young Ha Lee ◽  
In-Wook Choi ◽  
Bu Yeon Heo ◽  
Ju-Gyeong Kang ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Trichomonas Vaginalis ◽  
Parasitic Infection ◽  
Oxidase Inhibitor ◽  
Host Cells ◽  
Epithelial Cell Line ◽  
Dependent Manner ◽  
Siha Cells ◽  
Parasite Infections

Microbial adhesion is critical for parasitic infection and colonization of host cells. To study the host–parasite interaction in vitro, we established a flow cytometry-based assay to measure the adherence of Trichomonas vaginalis to epithelial cell line SiHa. SiHa cells and T. vaginalis were detected as clearly separated, quantifiable populations by flow cytometry. We found that T. vaginalis attached to SiHa cells as early as 30 min after infection and the binding remained stable up to several hours, allowing for analysis of drug treatment efficacy. Importantly, NADPH oxidase inhibitor DPI treatment induced the detachment of T. vaginalis from SiHa cells in a dose-dependent manner without affecting host cell viability. Thus, this study may provide an understanding for the potential development of therapies against T. vaginalis and other parasite infections.

scholarly journals VPTMdb: a viral posttranslational modification database

2020 ◽  
Author(s):  
Yujia Xiang ◽  
Quan Zou ◽  
Lilin Zhao
Keyword(s):  
Posttranslational Modifications ◽  
Posttranslational Modification ◽  
Drug Targets ◽  
Viral Infections ◽  
Interaction Analysis ◽  
Human Interaction ◽  
Host Cells ◽  
Phosphorylation Sites ◽  
Human Viruses ◽  
Disordered Regions

Abstract In viruses, posttranslational modifications (PTMs) are essential for their life cycle. Recognizing viral PTMs is very important for a better understanding of the mechanism of viral infections and finding potential drug targets. However, few studies have investigated the roles of viral PTMs in virus–human interactions using comprehensive viral PTM datasets. To fill this gap, we developed the first comprehensive viral posttranslational modification database (VPTMdb) for collecting systematic information of PTMs in human viruses and infected host cells. The VPTMdb contains 1240 unique viral PTM sites with 8 modification types from 43 viruses (818 experimentally verified PTM sites manually extracted from 150 publications and 422 PTMs extracted from SwissProt) as well as 13 650 infected cells’ PTMs extracted from seven global proteomics experiments in six human viruses. The investigation of viral PTM sequences motifs showed that most viral PTMs have the consensus motifs with human proteins in phosphorylation and five cellular kinase families phosphorylate more than 10 viral species. The analysis of protein disordered regions presented that more than 50% glycosylation sites of double-strand DNA viruses are in the disordered regions, whereas single-strand RNA and retroviruses prefer ordered regions. Domain–domain interaction analysis indicating potential roles of viral PTMs play in infections. The findings should make an important contribution to the field of virus–human interaction. Moreover, we created a novel sequence-based classifier named VPTMpre to help users predict viral protein phosphorylation sites. VPTMdb online web server (http://vptmdb.com:8787/VPTMdb/) was implemented for users to download viral PTM data and predict phosphorylation sites of interest.

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