Chinese Chemical Letters, Год журнала: 2023, Номер 34(10), С. 108359 - 108359
Опубликована: Март 21, 2023
Язык: Английский
Pathogens, Год журнала: 2024, Номер 13(10), С. 835 - 835
Опубликована: Сен. 27, 2024
The protozoan parasite Leishmania causes leishmaniasis, a neglected tropical disease, that disproportionately affects underdeveloped countries. This disease has major health, economic, and social implications, particularly because of the limited treatment options, high cost, severe side effects associated with available therapeutics, rate failure caused by parasites’ growing resistance to current medications. In this review, we describe first common strategies used pathogens develop drug then focus on arsenal drugs treat their modes action, molecular mechanisms contributing in spp., including role genomic, transcriptional, translational control. We more specifically our recent discovery reprogramming as driver leading coordinated changes translation transcripts orchestrating metabolome lipidome support resistance. A thorough understanding these is essential identify key elements needed combat improve leishmaniasis methods.
Язык: Английский
Процитировано
9
Antimicrobial Agents and Chemotherapy, Год журнала: 2024, Номер 68(3)
Опубликована: Фев. 13, 2024
ABSTRACT The problems associated with the drugs currently used to treat leishmaniasis, including resistance, toxicity, and high cost of some formulations, call for urgent identification new therapeutic agents novel modes action. aggregated protein dye YAT2150 has been found be a potent antileishmanial compound, half-maximal inhibitory concentration (IC 50 ) approximately 0.5 µM against promastigote amastigote stages Leishmania infantum . encapsulation in liposomes significantly improved its vitro IC 0.37 0.19 promastigotes amastigotes, respectively, increased cytotoxic human umbilical vein endothelial cells >50 µM. became strongly fluorescent when binding intracellular deposits cells. This fluorescence pattern aligns proposed mode action this drug malaria parasite Plasmodium falciparum , inhibition aggregation. In major rapidly reduced ATP levels, suggesting an alternative mechanism. To best our knowledge, first-in-class compound is only one described so far having significant activity both thus being potential treatment co-infections parasites.
Язык: Английский
Процитировано
6
Frontiers in Cellular and Infection Microbiology, Год журнала: 2022, Номер 12
Опубликована: Янв. 24, 2022
Leishmaniasis is one of the major public health concerns in Latin America, Africa, Asia, and Europe. The absence vaccines for human use lack effective vector control programs make chemotherapy main strategy to all forms disease. However, high toxicity available drugs, limited choice therapeutic agents, occurrence drug-resistant parasite strains are challenges related chemotherapy. Currently, only a small number drugs leishmaniasis treatment, including pentavalent antimonials (Sb V ), amphotericin B its formulations, miltefosine, paromomycin sulphate, pentamidine isethionate. In addition drug toxicity, failure serious concern. parasites causes closely diversity this genus. Owing enormous plasticity genome, resistance can occur by altering different metabolic pathways, demonstrating that mechanisms multifactorial extremely complex. Genetic variability genome cause not have limitations, but also search new challenging. Here, we examined biological characteristics hinder discovery.
Язык: Английский
Процитировано
21
Medicinal Research Reviews, Год журнала: 2023, Номер 44(3), С. 1055 - 1120
Опубликована: Дек. 24, 2023
Leishmaniasis is a group of neglected tropical diseases caused by at least 20 species Leishmania protozoa, which are spread the bite infected sandflies. There three main forms disease: cutaneous leishmaniasis (CL, most common), visceral (VL, also known as kala-azar, serious), and mucocutaneous leishmaniasis. One billion people live in areas endemic to leishmaniasis, with an annual estimation 30,000 new cases VL more than 1 million CL. New treatments for urgent need, existing ones inefficient, toxic, and/or expensive. We have revised experimental structure-based drug design (SBDD) efforts applied discovery drugs against grouped explored targets according metabolic pathways they belong to, key achieved advances highlighted evaluated. In cases, SBDD studies follow high-throughput screening campaigns secondary pharmacokinetic optimization, due majoritarian belief that there few validated However, some strategies significantly contributed candidates bigger number holds promise future development.
Язык: Английский
Процитировано
11
PLoS Pathogens, Год журнала: 2024, Номер 20(4), С. e1012181 - e1012181
Опубликована: Апрель 24, 2024
Addressing the challenges of quiescence and post-treatment relapse is utmost importance in microbiology field. This study shows that Leishmania infantum L. donovani parasites rapidly enter into after an estimated 2–3 divisions both human mouse bone marrow stem cells. Interestingly, this behavior not observed macrophages, which are primary host cells parasite. Transcriptional comparison quiescent non-quiescent metabolic states confirmed overall decrease gene expression as a hallmark quiescence. Quiescent amastigotes display reduced size signs rapid evolutionary adaptation response with genetic alterations. Our provides further evidence state significantly enhances resistance to treatment. Moreover, transitioning through highly compatible sand fly transmission increases potential infect Collectively, work identified niche where occurs, important implications for antiparasitic treatment acquisition virulence traits.
Язык: Английский
Процитировано
4
Microorganisms, Год журнала: 2023, Номер 11(9), С. 2248 - 2248
Опубликована: Сен. 7, 2023
Protozoan parasites are known for their remarkable capacity to persist within the bodies of vertebrate hosts, which frequently results in prolonged infections and recurrence diseases. Understanding molecular mechanisms that underlie event persistence is paramount significance develop innovative therapeutic approaches, given these pathways still need be thoroughly elucidated. The present article provides a comprehensive overview latest developments investigation protozoan hosts. focus primarily on function persisters, formation host, specific interactions between host parasite while they persist. Additionally, we examine metabolomic, transcriptional, translational changes undergo during focusing major such as Plasmodium spp., Trypanosoma Leishmania Toxoplasma spp. Key findings our study suggest deploy several physiological strategies evade immune surveillance sustain persistence. Furthermore, some stage differentiation, enabling them acclimate varying environments challenges. More often, stressors drug exposure were demonstrated impact persisters significantly. regulating hosts can reinvigorate current insights into host–parasite facilitate development more efficacious disease therapeutics.
Язык: Английский
Процитировано
9
Journal of Biological Chemistry, Год журнала: 2025, Номер unknown, С. 108208 - 108208
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
0
International Journal for Parasitology, Год журнала: 2025, Номер unknown
Опубликована: Апрель 1, 2025
Язык: Английский
Процитировано
0
Trends in Parasitology, Год журнала: 2025, Номер unknown
Опубликована: Май 1, 2025
Genome instability has been identified as a major driver of adaptation in fast-growing, eukaryotic cells, including fungi, protists, or cancer. How these cells cope with the toxic effects caused by such copy number variations remains to be elucidated. In recent years, protist parasites Leishmania spp. have emerged interesting model pathogens assess this open question and study role its intrinsic genome fitness gain culture, experimental infection, field. Here we summarize results on genomic propose thought-provoking evolutionary concepts new field that need considered when mapping genotype-to-phenotype relationships molecular epidemiological studies.
Язык: Английский
Процитировано
0
PLoS neglected tropical diseases, Год журнала: 2025, Номер 19(5), С. e0013108 - e0013108
Опубликована: Май 28, 2025
Leishmania spp. is the etiological agent of leishmaniases, neglected diseases that seek to be eradicated in coming years. The life cycle these parasites involves different host and stress environments. In recent years, many studies have shown several protein-coding genes are directly involved with development interactions. However, little still known about role non-coding RNAs (ncRNAs) progression. this study, we aimed identify genomic structure function ncRNAs from get insights into repertoire (RNAome) protozoan genus. We studied 26 strains corresponding 16 species . Our RNAome analysis revealed presence shared among species, allowing us differentiate between subgenera as well canonically related visceral leishmaniasis. also co-expression relationships coding which amastigote developmental stage for braziliensis donovani miRNA-like transcripts co-expressed starvation, survival histone modification. This work represents first effort characterize ssp. RNAome, supporting further approaches better understand gene regulation, infective process, host-parasite interaction.
Язык: Английский
Процитировано
0