Molecular and biochemical parasitology最新文献

{"title":"Inorganic phosphate transporter in Giardia duodenalis and its possible role in ATP synthesis","authors":"Ayra Diandra Carvalho-de-Araújo,&nbsp;Luiz Fernando Carvalho-Kelly,&nbsp;Claudia F. Dick,&nbsp;José Roberto Meyer-Fernandes","doi":"10.1016/j.molbiopara.2022.111504","DOIUrl":"10.1016/j.molbiopara.2022.111504","url":null,"abstract":"<div><p><span><em>Giardia duodenalis</em></span><span><span> is a flagellated protozoan that inhabits vertebrate host intestines, causing the disease known as </span>giardiasis. Similar to other parasites, </span><em>G. duodenalis</em> must take advantage of environmental resources to survive, such as inorganic phosphate (P_i) availability. P_i<span> is an anionic molecule and an essential nutrient for all organisms because it participates in the biosynthesis<span> of biomolecules, energy storage, and cellular structure formation. The first step in Pi metabolism is its uptake through specific transporters on the plasma membrane. We identified a symporter H</span></span>⁺:P_i-type ORF sequence in the <em>G. duodenalis</em> genome (GenBank ID: GL50803_5164), named <em>GdPho84,</em> which is homologous to <span><em>Saccharomyces cerevisiae</em></span> PHO84. In trophozoites, P_i transport was linear for up to 15 min, and the cell density was 3 × 10⁷ cells/ml. Physiological variations in pH (6.4–8.0) did not influence P_i uptake. This P_i transporter had a high affinity, with K_0.5 = 67.7 ± 7.1 µM P_i. SCH28080 (inhibitor of H⁺, K⁺<span>-ATPase), bafilomycin A</span>₁ (inhibitor of vacuolar H⁺-ATPase), and FCCP (H⁺ ionophore) were able to inhibit P_i transport, indicating that an H⁺ gradient in the cell powered uphill P_i movement. PAA, an H⁺-dependent P_i<span> transport inhibitor, reduced cell proliferation, P</span>_i transport activity, and GdPHO48 mRNA levels. P_i starvation stimulated membrane potential-sensitive P_i uptake coupled to H⁺ fluxes, increased <em>GdPho84</em> expression, and reduced intracellular ATP levels. These events indicate that these cells had an increased capacity to internalize P_i as a compensatory mechanism compared to cells maintained in control medium conditions. Internalized P_i<span> can be used in glycolytic metabolism once iodoacetamide (GAPDH inhibitor) inhibits P</span>_i influx. Together, these results reinforce the hypothesis that P_i is a crucial nutrient for <em>G. duodenalis</em> energy metabolism.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40621894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anisakis spp, DNA detection in paraffin-embedded tissue biopsies recovered from patients with gastritis using real-time PCR in Bushehr, Persian Gulf, Iran","authors":"Mohsen Najjari ,&nbsp;Seyed Mahmoud Sadjjadi ,&nbsp;Hossein Khodadadi ,&nbsp;Mohamad Reza Farzaneh ,&nbsp;Simonetta Mattiucci","doi":"10.1016/j.molbiopara.2022.111494","DOIUrl":"10.1016/j.molbiopara.2022.111494","url":null,"abstract":"<div><p><span>Anisakiasis is a zoonotic<span> fish-born parasitic disease<span> caused by anisakid nematodes. Paraffin-embedded blocks containing biopsy samples taken from patients suffering gastritis with unknown causes were investigated by real-time PCR, in the Bushehr region, Iran; where human anisakiasis has not been reported, so far. A total of 50 paraffin-embedded blocks were randomly selected from 250 archived blocks of the patients with gastritis. A SYBER green-based real-time PCR targeting the ITS1 region was developed for the identification of </span></span></span><span><em>Anisakis</em></span> genus. An 86 bp partial fragment of the <em>Anisakis</em> spp. ITS1 gene was amplified successfully. A total of 3 out of 50 samples (6 %) had positive amplification in the samples and their pathology reports showed a significant finding of moderate chronic gastritis with or without ulcers. In conclusion, the developed qPCR could be used for detecting <em>Anisakis</em><span> spp. larval DNA in human biopsy blocks. This study showed the hidden human cases of anisakiasis in the Bushehr for the first time.</span></p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40493687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, in vitro Schistosomicidal Activity and Ultrastructural Alterations Caused by Thiosemicarbazones and Thiazolidinones Against Juvenile and Adult Schistosoma mansoni Worms (Sambon, 1907).","authors":"Rubens Emanoel Tavares da Rocha, Antônio Sérgio Alves de Almeira Júnior, Nairomberg Cavalcanti Portela Junior, Amanda Vasconcelos do Nascimento, Nayara Maria Siqueira Leite, J. F. de Oliveira, M. D. C. Alves de Lima, A. Feitosa, Maria Eliane Bezerra de Mélo, F. Brayner, L. Alves","doi":"10.2139/ssrn.4061503","DOIUrl":"https://doi.org/10.2139/ssrn.4061503","url":null,"abstract":"Schistosomiasis is a neglected disease that affects about 258 million people worldwide. Caused by Schistosoma mansoni, helminth which, in Brazil, it is present on 19 states and capital. Praziquantel (PZQ) treatment presents low efficacy and adverse effects in parasites juvenile stages. Thiosemicarbazones and thiazolidinones are rising as potent chemical groups that have biological activity wide spectrum, and with radical modifications, they may become more effective and selective. Aiming to evaluate the action of these molecules against S. mansoni, JF series thiosemicarbazones and thiazolidinones (LqIT/UFPE) were synthesized: JF30, JF31, JF33, JF34, JF35, JF36, JF38, JF39, JF42 and JF43. Several parameters were evaluated, such as: their cytotoxicity in VERO cells, in vitro schistosomicidal activity for juvenile and adult worms and their action on worms through ultrastructural changes. Cytotoxicity indices ranged from 272µM to 725µM. When evaluating mortality rate, adult and juvenile worms showed 100% mortality rate within 24h and 48h, respectively, when exposed to the compounds JF31 and JF43 at a dose of 200µM. Also, motility, mortality and oviposition parameters were evaluated: JF31 and JF43 presented a score of 0 in 24h, meaning total absence of movement, whereas no eggs and soft tissue damage were observed under optical microscopy. Through scanning electron microscopy, integumentary alterations caused by the compounds JF31 and JF43 were observed, such as: exposure of the musculature, formation of integumentary bubbles, integuments with abnormal morphology and destruction of tubercles and spikes. The results shoerd that the compound JF31 was 2.39 times more selective for adult worms and JF43 was 3.74 times more selective for juvenile worms. Thus, the compounds JF43 and JF31 are the most promising for presenting schistosomicidal activity of S. mansoni.","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85470288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stress-responsive AMP Kinase like protein regulates encystation of Entamoeba invadens","authors":"Piyali Goswami,&nbsp;Sintu Kumar Samanta ,&nbsp;Tarun Agarwal,&nbsp;Sudip K. Ghosh","doi":"10.1016/j.molbiopara.2022.111507","DOIUrl":"10.1016/j.molbiopara.2022.111507","url":null,"abstract":"<div><p><span>Starvation is always accompanied by an increase in the ratio of AMP/ATP followed by activation of AMPK<span>. It is one of the sensors for cellular energy status and is highly conserved across various species. Its role in the stage differentiation process of protozoan species like </span></span><span><em>Giardia</em></span>, <span><em>Plasmodium, </em><em>Trypanosome</em><em>,</em></span> and <span><em>Toxoplasma</em></span> has been reported. Since <span><em>Entamoeba</em></span> undergoes encystation in glucose-starved conditions; it intrigued us to investigate the existence and role of AMPK during the differentiation of trophozoites to the cyst. By employing <em>in silico</em> approaches, we have identified an AMPK homologue which is denominated here as EiAMPK (AMPK-like protein in <span><em>Entamoeba invadens</em></span><span><span>). Sequence and structural analysis indicate that EiAMPK is sequentially and structurally similar to the AMPK alpha subunit of other organisms. The recombinant form of EiAMPK was functionally active and in accordance, its activity was inhibited by an AMPK-specific inhibitor (eg. Compound C). The increased expression of EiAMPK during different stresses indicated that EiAMPK is a stress-responsive gene. To further investigate, whether EiAMPK has any role in encystation, we employed RNAi-mediated </span>gene silencing that demonstrated its active involvement in encystation. It is known that </span><em>Entamoeba</em><span><span> maintains a flow of glucose from the glycolytic pathway to chitin synthesis for cyst wall formation during encystation. It is conceivable that EiAMPK might have a command over such </span>glucose metabolism. As anticipated, the chitin synthesis was found greatly inhibited in both EiAMPK knockdown and Compound C treated cells, indicating that EiAMPK regulates the cyst wall chitin synthesis.</span></p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40547739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deleting ku80 improves the efficiency of targeted gene editing in Neospora caninum","authors":"Kaijian Wu ,&nbsp;Xingju Song ,&nbsp;Yayun Wu ,&nbsp;Xu Yang ,&nbsp;Jing Liu ,&nbsp;Qun Liu","doi":"10.1016/j.molbiopara.2022.111508","DOIUrl":"10.1016/j.molbiopara.2022.111508","url":null,"abstract":"<div><p>CRISPR/Cas9 technology has been widely used for gene editing in organisms. Gene deletion of the <em>ku80/ku70</em> complex can improve the efficiency of gene replacement in <em>Arabidopsis thaliana</em>, <em>Cryptococcus neoformans</em>, and <em>Toxoplasma gondii</em>, which remained elusive in <em>Neospora caninum</em>. Here, we knock out the <em>ku80</em> gene in Nc1 strain by using CRISPR/Cas9, detect the growth rate and virulence of <em>Nc</em>Δ<em>ku80</em>. Then we compare the efficiency of gene replacements between <em>Nc</em>Δ<em>ku80</em> and Nc1 strains by transfected with the same HA-tagged plasmids, and the percentage of HA-tagged parasites was investigated by IFA. The results showed that gene targeting efficiency was increased in the <em>Nc</em>Δ<em>ku80</em> strain via double crossover at several genetic loci, but its growth rate and virulence were unaffected. In conclusion, the <em>Nc</em>Δ<em>ku80</em> strain can be used as an effective strain for rapid gene editing of <em>N. caninum</em>.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40610714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Schistosomiasis related circulating cell-free DNA: A useful biomarker in diagnostics","authors":"Hanif Ullah ,&nbsp;Safia Arbab ,&nbsp;Ka Li ,&nbsp;Muhammad Inayat Ullah Khan ,&nbsp;Abdul Qadeer ,&nbsp;Nehaz Muhammad","doi":"10.1016/j.molbiopara.2022.111495","DOIUrl":"10.1016/j.molbiopara.2022.111495","url":null,"abstract":"<div><p><span><em>Schistosoma</em></span><span> is a genus of trematodes causing schistosomiasis, a major neglected tropical disease infecting more than 240 million people and with 700 million people at the risk of infection in the tropical and subtropical regions of the world, especially low-income countries. For the elimination of the disease, accurate diagnostic tools are needed. Besides allowing early treatment, early detection prevents environmental contamination and in turn ensures safe water sources in the endemic areas. Cell-free DNA (cfDNA) biomarker detection is a relatively new tool, used for the diagnosis of schistosomiasis in the early stages of infection from non-invasive clinical or experimental samples. cfDNA can be detected in </span><em>Schistosoma</em> infected host body fluids such as urine, serum, saliva and tissues, mainly in blood offering significant benefits for accurate diagnosis. In the current review, we described different characteristics of cfDNA, evidencing and supporting its potential uses in <em>Schistosoma</em> diagnosis and the improvement of treatment effectiveness.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40522524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strongyloides spp. eliminate male-determining sperm post-meiotically","authors":"Alex Dulovic ,&nbsp;Iris Koch ,&nbsp;Katharina Hipp ,&nbsp;Adrian Streit","doi":"10.1016/j.molbiopara.2022.111509","DOIUrl":"10.1016/j.molbiopara.2022.111509","url":null,"abstract":"<div><p><span>If normal male meiosis occurs, it would be expected that 50 % of sperm lack an X chromosome (nullo X) and hence upon fertilisation, result in male progeny. However, for sexual reproduction within the free-living stages of </span><span><em>Strongyloides</em></span><span> spp. male offspring are absent. We had shown earlier by quantitative whole genome sequencing that within </span><em>Strongyloides</em> spp., nullo-X sperm are either absent (<em>S. papillosus</em>) or underrepresented (<em>S. ratti</em><span>) among mature sperm. To investigate how and when this elimination of male-determining sperm occurs, we characterised spermatogenesis<span><span> and the dynamic localisation of important molecular players such as tubulin, actin and major sperm protein by DIC microscopy, immunohistochemistry, and </span>fluorescent in situ hybridization (FISH) in </span></span><em>S. ratti</em>, <em>S. papillosus</em> and <em>Parastrongyloides trichosuri</em><span>. We found that meiotic divisions in these parasites proceeded as expected for organisms with XO males, resulting in four equally sized spermatocytes<span>, two with and two without an X chromosome. However, mature sperm were found to almost always contain an X chromosome. We also observed structures that contained protein constituents of sperm, such as actin and major sperm protein (MSP) but no DNA. These structures resemble </span></span><em>C. elegans</em> residual bodies in appearance and may assume their function. We hypothesize that spermatocytes without an X-chromosome undergo some form of programmed cell death and transform into these residual body-like structures. As in <em>C. elegans</em>, MSP is found in fibrous body-membranous organelles (FB-MOs). Knocking down MSP by RNAi showed that MSP is essential for fertility in <em>S. ratti</em>, as it is in <em>C. elegans</em>.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40709198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is Strongyloides stercoralis hyperinfection induced by glucocorticoids a result of both suppressed host immunity and altered parasite genetics?","authors":"De'Broski R. Herbert ,&nbsp;Jonathan D.C. Stoltzfus ,&nbsp;Heather L. Rossi ,&nbsp;David Abraham","doi":"10.1016/j.molbiopara.2022.111511","DOIUrl":"10.1016/j.molbiopara.2022.111511","url":null,"abstract":"<div><p>The gastrointestinal (GI) nematode <em>Strongyloides stercoralis</em> (<em>S.s.</em>) causes human strongyloidiasis, a potentially life-threatening disease that currently affects over 600 million people globally. The uniquely pernicious aspect of <em>S.s.</em> infection, as compared to all other GI nematodes, is its autoinfective larval stage (L3a) that maintains a low-grade chronic infection, allowing undetectable persistence for decades. Infected individuals who are administered glucocorticoid therapy can develop a rapid and often lethal hyperinfection syndrome within days. Hyperinfection patients often present with dramatic increases in first- and second-stage larvae and L3a in their GI tract, with L3a widely disseminating throughout host organs leading to sepsis. How glucocorticoid administration drives hyperinfection remains a critical unanswered question; specifically, it is unknown whether these steroids promote hyperinfection through eliminating essential host protective mechanisms and/or through dysregulating parasite development. This current deficiency in understanding is largely due to the previous absence of a genetically defined mouse model that would support all <em>S.s.</em> life-cycle stages and the lack of successful approaches for <em>S.s</em>. genetic manipulation. However, there are currently new possibilities through the recent demonstration that immunodeficient NOD.Cg-<em>Prkdc</em>^{<em>scid</em>} <em>Il2rg</em>^{<em>tm1Wjl</em>}/SzJ (NSG) mice support sub-clinical infections that can be transformed to lethal hyperinfection syndrome following glucocorticoid administration. This is coupled with advances in transcriptomics, transgenesis, and gene inactivation strategies that now allow rigorous scientific inquiry into <em>S.s.</em> biology. We propose that combining in vivo manipulation of host immunity and deep immunoprofiling strategies with the latest advances in <em>S.s.</em> transcriptomics, <em>piggyBac</em> transposon-mediated transgene insertion, and CRISPR/Cas-9-mediated gene inactivation will facilitate new insights into the mechanisms that could be targeted to block lethality in humans with <em>S.s.</em> hyperinfection.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0166685122000652/pdfft?md5=aad215055bfc5228af537b009938fce2&pid=1-s2.0-S0166685122000652-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40655719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased iron uptake in the bladder wall of racemose cysts of Taenia solium","authors":"Miguel A. Orrego ,&nbsp;Carlos M. Vasquez ,&nbsp;Kayla Togneri ,&nbsp;Juan P. Laclette ,&nbsp;Hector H. Garcia ,&nbsp;Theodore E. Nash ,&nbsp;for the Cysticercosis Working Group in Peru","doi":"10.1016/j.molbiopara.2022.111496","DOIUrl":"10.1016/j.molbiopara.2022.111496","url":null,"abstract":"<div><p>Racemose neurocysticercosis is an aggressive infection caused by the aberrant expansion and proliferation of the bladder wall of the <em>Taenia solium</em> cyst within the subarachnoid spaces of the human brain. The parasite develops and proliferates in a microenvironment with low concentrations of growth factors and micronutrients compared to serum. Iron is important for essential biological processes, but its requirement for racemose cyst viability and proliferation has not been studied. The presence of iron in the bladder wall of racemose and normal univesicular <em>T. solium</em> cysts was determined using Prussian blue staining. Iron deposits were readily detected in the bladder wall of racemose cysts but were not detectable in the bladder wall of univesicular cysts. Consistent with this finding, the genes for two iron-binding proteins (<em>ferritin</em> and <em>melanotransferrin</em>) and <em>ribonucleotide reductase</em> were markedly overexpressed in the racemose cyst compared to univesicular cysts. The presence of iron in the bladder wall of racemose cysts may be due to its increased metabolic rate due to proliferation.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9869405/pdf/nihms-1863889.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10505584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aminoacyl-tRNA synthetase (AARS) as an attractive drug target in neglected tropical trypanosomatid diseases-Leishmaniasis, Human African Trypanosomiasis and Chagas disease","authors":"Vikas Kushwaha,&nbsp;Neena Capalash","doi":"10.1016/j.molbiopara.2022.111510","DOIUrl":"10.1016/j.molbiopara.2022.111510","url":null,"abstract":"<div><p><span><span>TriTryp diseases (Leishmaniasis, Human African Trypanosomiasis (HAT), and Chagas disease) are devastating parasitic neglected tropical diseases (NTDs) that affect billions of people in developing countries, cause high mortality in humans, and impose a large socio-economic burden. The current treatment options against tritryp diseases are suboptimal and challenging due to the emergence of resistance against available tritryp drugs. Hence, designing and developing effective anti-tritryp drugs with novel targets are required. Aminoacyl-tRNA synthetases (AARSs) involved in specific aminoacylation of transfer RNAs (tRNAs), interrupt </span>protein synthesis through inhibitors, and retard the parasite growth. AaRSs have long been studied as therapeutic targets in bacteria, and three </span>aaRS<span> inhibitors, mupirocin (against IleRS), tavaborole AN2690 (against LeuRS), and halofuginone (against ProRS), are already in clinical practice. The structural differences between tritryp and human aaRSs and the presence of unique sequences (N-terminal domain/C-terminal domain/catalytic domain) make them potential target for developing selective inhibitors. Drugs based on a single aaRS target developed by high-throughput screening (HTS) are less effective due to the emergence of resistance. However, designing multi-targeted drugs may be a better strategy for resistance development. In this perspective, we discuss the characteristics of tritryp aaRSs, sequence conservation in their orthologs and their peculiarities, recent advancements towards the single-target and multi-target aaRS inhibitors developed through rational design.</span></p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40625827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}