Search Results (5)

Leishmania major is a unicellular protozoan that causes cutaneous leishmaniasis in mammals and is mainly transmitted by the sand fly Phlebotomus papatasi. However, the contribution of microRNAs (miRNAs) and protein-coding genes to its pathogenic mechanisms remains largely unexplored. In this study, we systematically analyzed miRNAs and protein-coding genes in L. major, its insect vector, and mammalian hosts. Comparative genomic analysis revealed 2963 conserved proteins shared among the three groups, highlighting a core set of proteins across protozoa, vectors, and hosts. Among mammals, human proteins exhibited the highest homology with L. major, while P. papatasi displayed the lowest proportion of homologs. Functional annotation of 94 hypothetical proteins identified 27 infection-related proteins, including 24 protein kinases and three tyrosine phosphatases, which may represent novel therapeutic targets. In addition, an EST-based approach identified 29 novel miRNAs in L. major. Phylogenetic analysis indicated that these miRNAs diverged into two distinct evolutionary branches, and homology analysis revealed that seven miRNAs were absent in all mammalian species. For example, miR-10117-3p was detected only in nematode Heligosmoides polygyrus. Furthermore, miRNA-gene interaction network analysis highlighted four key genes potentially involved in L. major infection. Collectively, our findings expand current knowledge of protozoan virulence by identifying novel miRNAs and infection-related proteins and provide promising candidates for future drug development against leishmaniasis. Full article

Leishmaniasis is a vector-borne parasitic disease caused by Leishmania spp., transmitted to humans by phlebotomine sand flies. The development of Leishmania into infective metacyclic promastigotes occurs within the sand fly gut, where the bacterial microbiota plays a pivotal role in parasite development and transmission dynamics. This study aimed to characterize the gut bacterial composition of phlebotomine sand flies collected from both endemic (Lalla Aaziza) and non-endemic (Marrakech) regions of leishmaniasis in Morocco. We investigated the microbiota of Phlebotomus papatasi, P. sergenti, P. perniciosus, and P. longicuspis, all proven vectors of cutaneous and visceral leishmaniasis in the Old World, including Morocco, as well as Sergentomyia minuta, a potential vector in the Mediterranean basin. Gut bacteria were isolated using conventional microbiological techniques and identified by MALDI-TOF mass spectrometry. Fifteen bacterial strains from three phyla were identified, with Bacillus pumilus being the most frequently detected species. Significant differences in colony-forming unit (CFU) counts and bacterial richness were observed between sand fly species and collection sites. Notably, Bacillus simplex (in P. papatasi), Nocardia ignorata (in P. sergenti), and Serratia spp. (in P. longicuspis) were identified for the first time in these vectors. This study is the first to investigate the gut bacterial composition of sand flies in Morocco, revealing species and locality-dependent differences in microbial communities. The predominance of Bacillus spp., particularly B. pumilus, suggests a potentially influential role in sand fly physiology and vector competence. Furthermore, the novel detection of B. simplex, N. ignorata, and Serratia spp. underscores previously unrecognized microbial associations that warrant further investigation. These findings provide a critical baseline for future studies exploring the microbiota-mediated modulation of sand fly–Leishmania interactions. Full article

The northern region of Brazil is endemic for American Tegumentary Leishmaniasis (ATL) primarily caused by Leishmania guyanensis and transmitted by the sand fly Nyssomyia umbratilis. The disease occurs at different rates in the municipalities of Manacapuru (MAN) and Rio Preto da Eva (RPE), located in the state of Amazonas. Despite their geographic proximity and separation by the Rio Negro, MAN has a low incidence, whereas RPE reports a significantly higher number of cases. Since the vector is present in both locations, potential biological differences in N. umbratilis may influence transmission. Previous studies suggested genotypic and phenotypic differences in N. umbratilis from both localities. To investigate the molecular factors underlying their potentially differential vectorial capacities, we performed a comparative proteomic analysis of dissected insect intestines from both localities. Our results revealed that sand flies from MAN showed a higher abundance of proteins related to gene transcription, protein translation, amino acid and proton transport, innate immune response and intestinal motility. Since the importance of microbiota has previously been shown in parasite–vector interactions, we also identified bacteria from both vector populations. We detected bacteria specific to each population and, exclusively in MAN, some species described in the literature as having parasiticidal properties. These findings highlight molecular and microbial peculiarities that could contribute to the observed difference in ATL prevalence in the two areas. Full article

Leishmaniasis is a tropical infectious disease caused by Leishmania parasites. The disease can be spread by the bite of an infected sand fly. Currently, five chemotherapeutic drugs are available in leishmaniasis treatment. However, these drugs exhibit toxicity and serious adverse effects on infected individuals, necessitating alternative treatment strategies. One such strategy involves using combinations of existing antileishmanial drugs. In this study, we evaluated the interaction between artesunate (AS) and three antileishmanial drugs—amphotericin B (AmB), miltefosine (MF), and paromomycin (PM) against Leishmania infantum. This evaluation marks the first time such an assessment has been conducted. The Chou–Talalay combination index method was employed to analyze the drug interaction. The findings revealed that the interaction between AS and AmB ranged from antagonistic to synergistic, while the interaction between AS and MF showed moderate to strong synergism. In contrast, the interaction between AS and PM resulted in an antagonistic interaction, which differs from the combinations with AmB or MF. This study provides valuable insights for developing novel drug regimens for leishmaniasis treatment, emphasizing the potential of AS and its combination with existing antileishmanial drugs. Further research is necessary to optimize drug combinations and minimize adverse effects, leading to more effective therapeutic outcomes. Full article

We previously showed that L. (Leishmania) amazonensis promastigotes and amastigotes of the PH8 strain generated larger lesions in mice than LV79, and that lesion-derived amastigotes from the two strains differ in their proteomes. We recently reported that PH8 promastigotes are more phagocytized by macrophages. Promastigotes’ membrane-enriched proteomes showed several differences, and samples of each strain clustered based on proteomes. In this paper, we show phenotypic differences between PH8 and LV79 promastigotes that may explain the higher virulence of PH8. We compared in vitro macrophage infections by day 4 (early) and day 6 (late stationary phase) cultures, resistance to complement, and LPG characteristics. PH8 promastigotes showed a higher infectivity and were more resistant to murine complement. LPG was different between the strains, which may influence the interaction with macrophages and survival to complement. We compared the infection of the permissive vector Lutzomyia longipalpis. PH8 was more abundant in the vector’s gut 72 h after feeding, which is a moment where blood digestion is finished and the parasites are exposed to the gut environment. Our results indicate that PH8 promastigotes are more infective, more resistant to complement, and infect the permissive vector more efficiently. These data suggest that PH8 is probably better adapted to the sand fly and more prone to survive in the vertebrate host. Full article