Leishmania infantum chagasi is the causative agent and Lutzomyia longipalpis is the main vector of visceral leishmaniasis in the Americas. We investigated the expression of Leishmania genes within L. longipalpis after artificial infection. mRNAs from genes involved in sugar and amino acid metabolism were upregulated at times of high parasite proliferation inside the insect. mRNAs from genes involved in metacyclogenesis had higher expression in late stages of infection. Other modulated genes of interest were involved in immunomodulation, purine salvage pathway and protein recycling. These data reveal aspects of the adaptation of the parasite to the microenvironment of the vector gut and reflect the preparation for infection in the vertebrate.

Charles University Faculty of Science Department of Parasitology Prague Czech Republic

Fundação Oswaldo Cruz Fiocruz Instituto Oswaldo Cruz Laboratório de Biologia Molecular de Parasitas e Vetores Rio de Janeiro RJ Brasil

Zobrazit více v PubMed

Telleria EL, Martins-da-Silva A, Tempone AJ, Traub-Cseko YM. Leishmania, microbiota and sand fly immunity. Parasitology. 2018;145(10):1336–1353. PubMed PMC

Alcolea PJ, Alonso A, Molina R, Jimenez M, Myler PJ, Larraga V. Functional genomics in sand fly-derived Leishmania promastigotes. PLoS Negl Trop Dis. 2019;13(5):e0007288. PubMed PMC

Inbar E, Hughitt VK, Dillon LA, Ghosh K, El-Sayed NM, Sacks DL. The Transcriptome of. Leishmania major developmental stages in their natural sand fly vector. mBio. 2017;8(2):e00029–e00017. PubMed PMC

Coutinho-Abreu IV, Serafim TD, Meneses C, Kamhawi S, Oliveira F, Valenzuela JG. Distinct gene expression patterns in vector-residing Leishmania infantum identify parasite stage-enriched markers. PLoS Negl Trop Dis. 2020;14(3):e0008014. PubMed PMC

Di-Blasi T, Telleria EL, Marques C, Couto RM, da Silva-Neves M, Jancarova M. Lutzomyia longipalpis TGF-beta has a role in Leishmania infantum chagasi survival in the vector. Front Cell Infect Microbiol. 2019;9:71–71. PubMed PMC

Rogers ME, Hajmova M, Joshi MB, Sadlova J, Dwyer DM, Volf P. Leishmania chitinase facilitates colonization of sand fly vectors and enhances transmission to mice. Cell Microbiol. 2008;10(6):1363–1372. PubMed PMC

Joshi MB, Rogers ME, Shakarian AM, Yamage M, Al-Harthi SA, Bates PA. Molecular characterization, expression, and in vivo analysis of LmexCht1 the chitinase of the human pathogen, Leishmania mexicana. J Biol Chem. 2005;280(5):3847–3861. PubMed PMC

Killick-Kendrick R, Molyneux DH, Ashford RW. Leishmania in phlebotomid sandflies I. Modifications of the flagellum associated with attachment to the mid-gut and oesophageal valve of the sandfly. Proc R Soc Lond B Biol Sci. 1974;187(1089):409–419. PubMed

Di-Blasi T, Lobo AR, Nascimento LM, Cordova-Rojas JL, Pestana K, Marin-Villa M. The flagellar protein FLAG1/SMP1 is a candidate for Leishmania-sand fly interaction. Vector Borne Zoonotic Dis. 2015;15(3):202–209. PubMed PMC

Salles BCS, Dias DS, Steiner BT, Lage DP, Ramos FF, Ribeiro PAF. Potential application of small myristoylated protein-3 evaluated as recombinant antigen and a synthetic peptide containing its linear B-cell epitope for the serodiagnosis of canine visceral and human tegumentary leishmaniasis. Immunobiology. 2019;224(1):163–171. PubMed

Dostalova A, Volf P. Leishmania development in sand flies parasite-vector interactions overview. Parasit Vectors. 2012;5:276–276. PubMed PMC

Schlein Y, Jacobson RL, Messer G. Leishmania infections damage the feeding mechanism of the sandfly vector and implement parasite transmission by bite. Proc Natl Acad Sci USA. 1992;89(20):9944–9948. PubMed PMC

Rodriguez-Contreras D, Aslan H, Feng X, Tran K, Yates PA, Kamhawi S. Regulation and biological function of a flagellar glucose transporter in Leishmania mexicana a potential glucose sensor. FASEB J. 2015;29(1):11–24. PubMed PMC

Gossage SM, Rogers ME, Bates PA. Two separate growth phases during the development of Leishmania in sand flies implications for understanding the life cycle. Int J Parasitol. 2003;33(10):1027–1034. PubMed PMC

Munoz C, San Francisco J, Gutierrez B, Gonzalez J. Role of the ubiquitin-proteasome systems in the biology and virulence of protozoan parasites. Biomed Res Int. 2015;2015:141526–141526. PubMed PMC

Silva-Jardim I, Horta MF, Ramalho-Pinto FJ. The Leishmania chagasi proteasome role in promastigotes growth and amastigotes survival within murine macrophages. Acta Trop. 2004;91(2):121–130. PubMed

Sadlova J, Price HP, Smith BA, Votypka J, Volf P, Smith DF. The stage-regulated HASPB and SHERP proteins are essential for differentiation of the protozoan parasite Leishmania major in its sand fly vector, Phlebotomus papatasi. Cell Microbiol. 2010;12(12):1765–1779. PubMed PMC

Doehl JS, Sadlova J, Aslan H, Pruzinova K, Metangmo S, Votypka J. Leishmania HASP and SHERP genes are required for in vivo differentiation, parasite transmission and virulence attenuation in the host. PLoS Pathog. 2017;13(1):e1006130. PubMed PMC

Moore B, Miles AJ, Guerra-Giraldez C, Simpson P, Iwata M, Wallace BA. Structural basis of molecular recognition of the Leishmania small hydrophilic endoplasmic reticulum-associated protein (SHERP) at membrane surfaces. J Biol Chem. 2011;286(11):9246–9256. PubMed PMC

Boitz JM, Ullman B. A conditional mutant deficient in hypoxanthine-guanine phosphoribosyltransferase and xanthine phosphoribosyltransferase validates the purine salvage pathway of Leishmania donovani. J Biol Chem. 2006;281(23):16084–16089. PubMed

Carter NS, Yates PA, Gessford SK, Galagan SR, Landfear SM, Ullman B. Adaptive responses to purine starvation in Leishmania donovani. Mol Microbiol. 2010;78(1):92–107. PubMed PMC

Serafim TD, Figueiredo AB, Costa PA, Marques-da-Silva EA, Goncalves R, de Moura SA. Leishmania metacyclogenesis is promoted in the absence of purines. PLoS Negl Trop Dis. 2012;6(9):e1833. PubMed PMC

Goldman-Pinkovich A, Balno C, Strasser R, Zeituni-Molad M, Bendelak K, Rentsch D. An arginine deprivation response pathway is induced in Leishmania during macrophage invasion. PLoS Pathog. 2016;12(4):e1005494. PubMed PMC

Aoki JI, Muxel SM, Zampieri RA, Acuna SM, Fernandes JCR, Vanderlinde RH. L-arginine availability and arginase activity characterization of amino acid permease 3 in Leishmania amazonensis. PLoS Negl Trop Dis. 2017;11(10):e0006025. PubMed PMC

Telleria EL, de Araujo AP, Secundino NF. d'Avila-Levy CM.Traub-Cseko YM Trypsin-like serine proteases in Lutzomyia longipalpis - expression, activity and possible modulation by Leishmania infantum chagasi. PLoS One. 2010;5(5):e10697. PubMed PMC

Diaz-Albiter H. Sant'Anna MR.Genta FA.Dillon RJ Reactive oxygen species-mediated immunity against Leishmania mexicana and Serratia marcescens in the sand phlebotomine fly Lutzomyia longipalpis. J Biol Chem. 2012;287(28):23995–24003. PubMed PMC

Alcolea PJ, Alonso A, Garcia-Tabares F, Mena MC, Ciordia S, Larraga V. Increased abundance of proteins involved in resistance to oxidative and nitrosative stress at the last stages of growth and development of Leishmania amazonensis promastigotes revealed by proteome analysis. PLoS One. 2016;11(10):e0164344. PubMed PMC

Matos DCS, Faccioli LAP, Cysne-Finkelstein L, De Luca PM, Corte-Real S, Armôa GRG. Kinetoplastid membrane protein-11 is present in promastigotes and amastigotes of Leishmania amazonensis and its surface expression increases during metacyclogenesis. Mem Inst Oswaldo Cruz. 2010;105(3):341–347. PubMed

Lacerda DI, Cysne-Finkelstein L, Nunes MP, De-Luca PM, Genestra MS, Leon LLP. Kinetoplastid membrane protein-11 exacerbates infection with Leishmania amazonensis in murine macrophages. Mem Inst Oswaldo Cruz. 2012;107(2):238–245. PubMed

Nandan D, Yi T, Lopez M, Lai C, Reiner NE. Leishmania EF-1alpha activates the Src homology 2 domain containing tyrosine phosphatase SHP-1 leading to macrophage deactivation. J Biol Chem. 2002;277(51):50190–50197. PubMed

Forrest DM, Batista M, Marchini FK, Tempone AJ, Traub-Cseko YM. Proteomic analysis of exosomes derived from procyclic and metacyclic-like cultured Leishmania infantum chagasi. J Proteomics. 2020;227:103902–103902. PubMed

Joshi PB, Kelly BL, Kamhawi S, Sacks DL, McMaster WR. Targeted gene deletion in Leishmania major identifies leishmanolysin (GP63) as a virulence factor. Mol Biochem Parasitol. 2002;120(1):33–40. PubMed

Hajmova M, Chang KP, Kolli B, Volf P. Down-regulation of gp63 in Leishmania amazonensis reduces its early development in Lutzomyia longipalpis. Microbes Infect. 2004;6(7):646–649. PubMed

Soares RP, Altoe ECF, Ennes-Vidal V, da Costa SM, Rangel EF, de Souza NA. In vitro inhibition of Leishmania attachment to sandfly midguts and LL-5 cells by divalent metal chelators, anti-gp63 and phosphoglycans. Protist. 2017;168(3):326–334. PubMed