| Author | Silva, Monique Florêncio da | |
| Author | Chagas, Marne Coimbra Batalha | |
| Author | Costa, Anderson Guimarães Baptista | |
| Author | Silva, Jullyanna Oliveira da | |
| Author | Waclawiak, Ingrid | |
| Author | Oliveira, Thamara Kelcya Fonseca de | |
| Author | Saraiva, Elvira Maria | |
| Author | Mesquita, Anita Leocadio Freitas | |
| Author | Fernandes, José Roberto Meyer | |
| Author | Silva, Laura Aragão de Farias | |
| Author | Trindade, Camilly Enes | |
| Author | Cuervo Escobar, Patricia | |
| Author | Nascimento, Renata Azevedo do | |
| Author | Moreira, Otacilio da Cruz | |
| Author | Gomes, Flávia Lima Ribeiro | |
| Author | Csekö, Yara Maria Traub | |
| Author | Telleria, Erich Loza | |
| Author | Vaselek, Slavica | |
| Author | Leštinová, Tereza | |
| Author | Volf, Petr | |
| Author | Späth, Gerald Frank | |
| Author | Cupolillo, Elisa | |
| Author | Boité, Mariana Côrtes | |
| Access date | 2025-04-01T16:15:00Z | |
| Available date | 2025-04-01T16:15:00Z | |
| Document date | 2025 | |
| 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. | |
| ISSN | 1553-7366 | |
| URI | https://www.arca.fiocruz.br/handle/icict/69326 | |
| Description | 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. | en_US |
| Description | Produção científica do Laboratório de Biologia Molecular de Parasitos e Vetores. | pt_BR |
| Description | Produção científica do Laboratório de Pesquisa em Leishmaniose. | pt_BR |
| Description | Produção científica do Laboratório de Pesquisa em Malária. | pt_BR |
| Description | Produção científica do Laboratório de Virologia e Parasitologia Molecular. | pt_BR |
| Sponsorship | This work received fund from: PTR (Programmes Tranversaux de Recherche) from Institut Pasteur Paris [grant number PTR 425-21 to Mariana Côrtes Boité and Gerald Frank Späth]; FIOCRUZ - PAEF [grant number IOC-023-FIO-18-2-63 to Elisa Cupolillo]; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) [grant number Finance Code 001 to Elisa Cupolillo]; Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) [grant number CNE E26-202.569/2019, ColBio2020 E26-210.285/2021, FAPERJ Emergentes E-26/010.002168/2019 to Elisa Cupolillo; and CNE 26/200.487/2023 to Patricia Cuervo Escobar]; Czech Ministry of Education and ERD funds [grant number CePaViP Z.02.1.01/0.0/0.0/16_019/0000759 to Erich Loza Telleria and Petr Volf]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. | |
| Language | eng | en_US |
| Publisher | Public Library of Science | |
| Rights | open access | |
| Subject in Portuguese | Doenças parasitárias | pt_BR |
| Subject in Portuguese | Flebotomíneos | pt_BR |
| Subject in Portuguese | Leishmania infantum | pt_BR |
| Subject in Portuguese | Ciclos de vida parasíticos | pt_BR |
| Subject in Portuguese | Macrófagos | pt_BR |
| Subject in Portuguese | Leishmania | pt_BR |
| Subject in Portuguese | Neutrófilos | pt_BR |
| Subject in Portuguese | Purinas | pt_BR |
| Title | Gene deletion as a possible strategy adopted by new world Leishmania infantum to maximize geographic dispersion | en_US |
| Type | Preprint | |
| DOI | 10.1371/journal.ppat.1012938 | |
| 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. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Leishmaniose. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Programa de Pós-Graduação em Biologia Celular e Molecular. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Leishmaniose. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Microbiologia Paulo de Góes. Laboratório de Imunologia das Leishmanioses. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Microbiologia Paulo de Góes. Laboratório de Imunologia das Leishmanioses. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Microbiologia Paulo de Góes. Laboratório de Imunologia das Leishmanioses. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Microbiologia Paulo de Góes. Laboratório de Imunologia das Leishmanioses. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Microbiologia Paulo de Góes. Laboratório de Imunologia das Leishmanioses. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Leishmaniose. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Leishmaniose. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Leishmaniose. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Leishmaniose. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia e Parasitologia Molecular. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Malária. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular de Parasitos e Vetores. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Charles University. Faculty of Science. Department of Parasitology. Prague, Czech Republic. | |
| Affilliation | Charles University. Faculty of Science. Department of Parasitology. Prague, Czech Republic. | |
| Affilliation | Charles University. Faculty of Science. Department of Parasitology. Prague, Czech Republic. | |
| Affilliation | Charles University. Faculty of Science. Department of Parasitology. Prague, Czech Republic. | |
| Affilliation | Univerisité Paris Cité. Institut Pasteur. Unité de Parasitologie Moléculaire et Signalisation. Paris, France. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Leishmaniose. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Fiocruz Rondônia. Instituto Nacional de Epidemiologia na Amazônia Ocidental. Porto Velho, RO, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Leishmaniose. Rio de Janeiro, RJ, Brasil. | |
| Subject | Parasitic diseases | en_US |
| Subject | Sand flies | en_US |
| Subject | Leishmania infantum | en_US |
| Subject | Parasitic life cycles | en_US |
| Subject | Macrophages | en_US |
| Subject | Leishmania | en_US |
| Subject | Neutrophils | en_US |
| Subject | Purines | en_US |
| e-ISSN | 1553-7374 | |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
| xmlui.metadata.dc.subject.ods | 09 Indústria, inovação e infraestrutura | |
| xmlui.metadata.dc.subject.ods | 17 Parcerias e meios de implementação | |
