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GENE DELETION AS A POSSIBLE STRATEGY ADOPTED BY NEW WORLD LEISHMANIA INFANTUM TO MAXIMIZE GEOGRAPHIC DISPERSION
Flebotomíneos
Leishmania infantum
Ciclos de vida parasíticos
Macrófagos
Leishmania
Neutrófilos
Purinas
Sand flies
Leishmania infantum
Parasitic life cycles
Macrophages
Leishmania
Neutrophils
Purines
Produção científica do Laboratório de Biologia Molecular de Parasitos e Vetores.
Produção científica do Laboratório de Pesquisa em Leishmaniose.
Produção científica do Laboratório de Pesquisa em Malária.
Produção científica do Laboratório de Virologia e Parasitologia Molecular.
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Abstract
Background: The present study investigates implications of a sub-chromosomal deletion in Leishmania infantum strains, the causative agent of American Visceral Leishmaniasis (AVL). Primarily found in New World strains, the deletion leads to the absence of the ecto-3'-nucleotidase/nuclease enzyme, impacting parasite virulence, pathogenicity, and drug susceptibility. The factors favoring prevalence and the widespread geographic distribution of these deleted mutant parasites (DEL) in the NW (NW) are discussed under the generated data. Methods: We conducted phenotypic assessments of the sub-chromosomal deletion through in vitro assays with axenic parasites and experimental infections in both in vitro and in vivo models of vertebrate and invertebrate hosts using geographically diverse mutant field isolates. Results: Despite reduced pathogenicity, the DEL strains efficiently infect vertebrate hosts and exhibit relevant differences, including enhanced metacyclogenesis and colonization rates in sand flies, potentially facilitating transmission. This combination may represent a more effective way to maintain and disperse the transmission cycle of DEL strains. Conclusions: Phenotypic assessments reveal altered parasite fitness, with potential enhanced transmissibility at the population level. Reduced susceptibility of DEL strains to miltefosine, a key drug in VL treatment, further complicates control efforts. The study underscores the importance of typing parasite genomes for surveillance and control, advocating for the sub-chromosomal deletion as a molecular marker in AVL management.
Keywords in Portuguese
Doenças parasitáriasFlebotomíneos
Leishmania infantum
Ciclos de vida parasíticos
Macrófagos
Leishmania
Neutrófilos
Purinas
Keywords
Parasitic diseasesSand flies
Leishmania infantum
Parasitic life cycles
Macrophages
Leishmania
Neutrophils
Purines
Publisher
Public Library of Science
Citation
SILVA, Monique Florêncio da et al. Gene deletion as a possible strategy adopted by new world Leishmania infantum to maximize geographic dispersion. PLoS Pathogens, v. 21, n. 3, p. 1-22, 20 Mar. 2025.DOI
10.1371/journal.ppat.1012938ISSN
1553-7366Notes
Author summary: Leishmaniasis is a serious disease affecting people in the Americas and other continents caused by a parasite called Leishmania infantum. This study explores how a specific genetic change in the parasite, known as a sub-chromosomal deletion, affects its behavior. This deletion leads to the loss of an enzyme called ecto-3'-nucleotidase/nuclease, which plays a role in the parasite's biology and ability to cause disease and respond to treatment. The study examined how this genetic change influences the parasite’s ability to infect cells and the sand flies that spread the parasite. They found that, although these mutant parasites (called DEL strains) are less harmful in some ways, they are better at completing their life cycle in sand flies and can thus spread more efficiently. Additionally, these DEL strains are less susceptible to miltefosine, a key drug used to treat the disease, making it harder to control. The findings suggest that the genetic change helps the parasite spread and survive, despite reducing its ability to infect cells. The study emphasizes the importance of identifying these genetic changes in studies that perform disease tracking and evaluate treatment strategies, suggesting that the deletion in American parasites could serve as a marker for better managing this challenging disease.Produção científica do Laboratório de Biologia Molecular de Parasitos e Vetores.
Produção científica do Laboratório de Pesquisa em Leishmaniose.
Produção científica do Laboratório de Pesquisa em Malária.
Produção científica do Laboratório de Virologia e Parasitologia Molecular.
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