The co-infection cases involving dixenous Leishmania spp. (mostly of the L. donovani complex) and presumably monoxenous trypanosomatids in immunocompromised mammalian hosts including humans are well documented. The main opportunistic parasite has been identified as Leptomonas seymouri of the sub-family Leishmaniinae. The molecular mechanisms allowing a parasite of insects to withstand elevated temperature and substantially different conditions of vertebrate tissues are not understood. Here we demonstrate that L. seymouri is well adapted for the environment of the warm-blooded host. We sequenced the genome and compared the whole transcriptome profiles of this species cultivated at low and high temperatures (mimicking the vector and the vertebrate host, respectively) and identified genes and pathways differentially expressed under these experimental conditions. Moreover, Leptomonas seymouri was found to persist for several days in two species of Phlebotomus spp. implicated in Leishmania donovani transmission. Despite of all these adaptations, L. seymouri remains a predominantly monoxenous species not capable of infecting vertebrate cells under normal conditions.

Biology Centre Institute of Parasitology Czech Academy of Sciences České Budějovice Czech Republic; Canadian Institute for Advanced Research Toronto Ontario Canada

Department of Parasitology Faculty of Science Charles University Prague Czech Republic

Department of Parasitology Faculty of Science Charles University Prague Czech Republic; Biology Centre Institute of Parasitology Czech Academy of Sciences České Budějovice Czech Republic

e Duve Institute and Université catholique de Louvain Brussels Belgium

Life Science Research Centre Faculty of Science University of Ostrava Ostrava Czech Republic

Life Science Research Centre Faculty of Science University of Ostrava Ostrava Czech Republic; Biology Centre Institute of Parasitology Czech Academy of Sciences České Budějovice Czech Republic

Life Science Research Centre Faculty of Science University of Ostrava Ostrava Czech Republic; Biology Centre Institute of Parasitology Czech Academy of Sciences České Budějovice Czech Republic; Department of Pathology Albert Einstein College of Medicine Bronx New York United States of America

Life Science Research Centre Faculty of Science University of Ostrava Ostrava Czech Republic; Zoological Institute of the Russian Academy of Sciences St Petersburg Russia

Zobrazit více v PubMed

Podlipaev SA (2001) The more insect trypanosomatids under study-the more diverse Trypanosomatidae appears. Int J Parasitol 31: 648–652. PubMed

Maslov DA, Votýpka J, Yurchenko V, Lukeš J (2013) Diversity and phylogeny of insect trypanosomatids: all that is hidden shall be revealed. Trends Parasitol 29: 43–52. 10.1016/j.pt.2012.11.001 PubMed DOI

Simpson AG, Stevens JR, Lukeš J (2006) The evolution and diversity of kinetoplastid flagellates. Trends Parasitol 22: 168–174. PubMed

Lukeš J, Skalický T, Týč J, Votýpka J, Yurchenko V (2014) Evolution of parasitism in kinetoplastid flagellates. Mol Biochem Parasitol 195: 115–122. 10.1016/j.molbiopara.2014.05.007 PubMed DOI

Laveran A, Franchini G (1920) Infections experimentales de chiens et de cobayes a l'aide de cultures d

McGhee RB, Cosgrove WB (1980) Biology and physiology of the lower Trypanosomatidae. Microbiol Rev 44: 140–173. PubMed PMC

Pacheco RS, Marzochi MC, Pires MQ, Brito CM, Madeira Md, et al. (1998) Parasite genotypically related to a monoxenous trypanosomatid of dog's flea causing opportunistic infection in an HIV positive patient. Mem Inst Oswaldo Cruz 93: 531–537. PubMed

Morio F, Reynes J, Dollet M, Pratlong F, Dedet JP, et al. (2008) Isolation of a protozoan parasite genetically related to the insect trypanosomatid PubMed DOI PMC

Ferreira MS, Borges AS (2002) Some aspects of protozoan infections in immunocompromised patients- a review. Mem Inst Oswaldo Cruz 97: 443–457. PubMed

Dedet JP, Pratlong F (2000) PubMed

Sundar S, Chakravarty J (2012) Recent advances in the diagnosis and treatment of kala-azar. Natl Med J India 25: 85–89. PubMed

Wallace FG, Hertig M (1968) Ultrastructural comparison of promastigote flagellates (leptomonads) of wild-caught Panamanian PubMed

Bhattarai NR, Das ML, Rijal S, van der Auwera G, Picado A, et al. (2009) Natural infection of PubMed DOI

Ghosh S, Banerjee P, Sarkar A, Datta S, Chatterjee M (2012) Coinfection of PubMed DOI PMC

Jirků M, Yurchenko VY, Lukeš J, Maslov DA (2012) New species of insect trypanosomatids from Costa Rica and the proposal for a new subfamily within the Trypanosomatidae. J Eukaryot Microbiol 59: 537–547. 10.1111/j.1550-7408.2012.00636.x PubMed DOI

Wallace FG (1977) PubMed

Votýpka J, Klepetková H, Yurchenko VY, Horák A, Lukeš J, et al. (2012) Cosmopolitan distribution of a trypanosomatid PubMed DOI

Conchon I, Campaner M, Sbravate C, Camargo EP (1989) Trypanosomatids, other than

Singh N, Chikara S, Sundar S (2013) SOLiD sequencing of genomes of clinical isolates of PubMed DOI PMC

Srivastava P, Prajapati VK, Vanaerschot M, Van der Auwera G, Dujardin JC, et al. (2010) Detection of PubMed DOI PMC

De Sa MF, De Sa CM, Veronese MA, Filho SA, Gander ES (1980) Morphologic and biochemical characterization of PubMed

Roitman I, Mundim MH, De Azevedo HP, Kitajima EW (1977) Growth of

McGhee RB (1959) The infection of avian embryos with PubMed

Kostygov AY, Grybchuk-Ieremenko A, Malysheva MN, Frolov AO, Yurchenko V (2014) Molecular revision of the genus PubMed DOI

Maslov DA, Yurchenko VY, Jirků M, Lukeš J (2010) Two new species of trypanosomatid parasites isolated from Heteroptera in Costa Rica. J Eukaryot Microbiol 57: 177–188. 10.1111/j.1550-7408.2009.00464.x PubMed DOI

Yurchenko V, Lukeš J, Jirků M, Zeledon R, Maslov DA (2006) PubMed

Yurchenko V, Votýpka J, Tesařová M, Klepetková H, Kraeva N, et al. (2014) Ultrastructure and molecular phylogeny of four new species of monoxenous trypanosomatids from flies (Diptera: Brachycera) with redefinition of the genus PubMed

Votýpka J, d'Avila-Levy CM, Grellier P, Maslov DA, Lukeš J, et al. (2015) New approaches to systematics of Trypanosomatidae: criteria for taxonomic (re)description. Trends Parasitol (in press). PubMed

Borghesan TC, Ferreira RC, Takata CS, Campaner M, Borda CC, et al. (2013) Molecular phylogenetic redefinition of PubMed DOI

El-Sayed NM, Myler PJ, Blandin G, Berriman M, Crabtree J, et al. (2005) Comparative genomics of trypanosomatid parasitic protozoa. Science 309: 404–409. PubMed

Porcel BM, Denoeud F, Opperdoes FR, Noel B, Madoui M-A, et al. (2014) The streamlined genome of PubMed DOI PMC

Ivens AC, Peacock CS, Worthey EA, Murphy L, Aggarwal G, et al. (2005) The genome of the kinetoplastid parasite, PubMed PMC

Mair G, Shi H, Li H, Djikeng A, Aviles HO, et al. (2000) A new twist in trypanosome RNA metabolism: cis-splicing of pre-mRNA. RNA 6: 163–169. PubMed PMC

Alves JM, Klein CC, da Silva FM, Costa-Martins AG, Serrano MG, et al. (2013) Endosymbiosis in trypanosomatids: the genomic cooperation between bacterium and host in the synthesis of essential amino acids is heavily influenced by multiple horizontal gene transfers. BMC Evol Biol 13: 190 10.1186/1471-2148-13-190 PubMed DOI PMC

Hannaert V, Bringaud F, Opperdoes FR, Michels PA (2003) Evolution of energy metabolism and its compartmentation in Kinetoplastida. Kinetoplastid Biol Dis 2: 11 PubMed PMC

Opperdoes FR, Coombs GH (2007) Metabolism of PubMed

Opperdoes FR, Szikora JP (2006) PubMed

Alves JM, Voegtly L, Matveyev AV, Lara AM, da Silva FM, et al. (2011) Identification and phylogenetic analysis of heme synthesis genes in trypanosomatids and their bacterial endosymbionts. PLoS One 6: e23518 10.1371/journal.pone.0023518 PubMed DOI PMC

Kořený L, Lukeš J, Oborník M (2010) Evolution of the haem synthetic pathway in kinetoplastid flagellates: an essential pathway that is not essential after all? Int J Parasitol 40: 149–156. 10.1016/j.ijpara.2009.11.007 PubMed DOI

Kořený L, Oborník M, Lukeš J (2013) Make it, take it, or leave it: heme metabolism of parasites. PLoS Pathog 9: e1003088 10.1371/journal.ppat.1003088 PubMed DOI PMC

Bartholomeu DC, de Paiva RM, Mendes TA, DaRocha WD, Teixeira SM (2014) Unveiling the intracellular survival gene kit of trypanosomatid parasites. PLoS Pathog 10: e1004399 10.1371/journal.ppat.1004399 PubMed DOI PMC

Maslov DA, Westenberger SJ, Xu X, Campbell DA, Sturm NR (2007) Discovery and barcoding by analysis of spliced leader RNA gene sequences of new isolates of Trypanosomatidae from Heteroptera in Costa Rica and Ecuador. J Eukaryot Microbiol 54: 57–65. PubMed

Ibrahim EA, Molyneux DH (1987) Pathogenicity of PubMed

Schaub GA (1994) Pathogenicity of trypanosomatids on insects. Parasitol Today 10: 463–468. PubMed

Alcolea PJ, Alonso A, Garcia-Tabares F, Torano A, Larraga V (2014) An insight into the proteome of PubMed DOI PMC

Mizbani A, Taslimi Y, Zahedifard F, Taheri T, Rafati S (2011) Effect of A2 gene on infectivity of the nonpathogenic parasite PubMed DOI

Gabernet-Castello C, Dacks JB, Field MC (2009) The single ENTH-domain protein of trypanosomes; endocytic functions and evolutionary relationship with epsin. Traffic 10: 894–911. 10.1111/j.1600-0854.2009.00910.x PubMed DOI

Bessat M, Knudsen G, Burlingame AL, Wang CC (2013) A minimal anaphase promoting complex/cyclosome (APC/C) in PubMed DOI PMC

Lye LF, Owens K, Shi H, Murta SM, Vieira AC, et al. (2010) Retention and loss of RNA interference pathways in trypanosomatid protozoans. PLoS Pathog 6: e1001161 10.1371/journal.ppat.1001161 PubMed DOI PMC

Zangger H, Ronet C, Desponds C, Kuhlmann FM, Robinson J, et al. (2013) Detection of Leishmania RNA virus in PubMed DOI PMC

Ives A, Ronet C, Prevel F, Ruzzante G, Fuertes-Marraco S, et al. (2011) PubMed DOI PMC

Votýpka J, Suková E, Kraeva N, Ishemgulova A, Duží I, et al. (2013) Diversity of trypanosomatids (Kinetoplastea: Trypanosomatidae) parasitizing fleas (Insecta: Siphonaptera) and description of a new genus PubMed DOI

Weeks R, Aline RF Jr., Myler PJ, Stuart K (1992) LRV1 viral particles in PubMed PMC

Salinas G, Zamora M, Stuart K, Saravia N (1996) Leishmania RNA viruses in PubMed

Evans E, Rawicz W, Smith BA (2013) Back to the future: mechanics and thermodynamics of lipid biomembranes. Faraday Discuss 161: 591–611. PubMed

Xu W, Hsu FF, Baykal E, Huang J, Zhang K (2014) Sterol biosynthesis is required for heat resistance but not extracellular survival in PubMed DOI PMC

Perez-Moreno G, Sealey-Cardona M, Rodrigues-Poveda C, Gelb MH, Ruiz-Perez LM, et al. (2012) Endogenous sterol biosynthesis is important for mitochondrial function and cell morphology in procyclic forms of PubMed DOI

Grant KM, Dunion MH, Yardley V, Skaltsounis AL, Marko D, et al. (2004) Inhibitors of PubMed PMC

Bates PA, Rogers ME (2004) New insights into the developmental biology and transmission mechanisms of PubMed

Lee SH, Stephens JL, Englund PT (2007) A fatty-acid synthesis mechanism specialized for parasitism. Nat Rev Microbiol 5: 287–297. PubMed

Coombs GH, Craft JA, Hart DT (1982) A comparative study of PubMed

Goad LJ, Holz GG Jr., Beach DH (1984) Sterols of PubMed

Coppens I, Courtoy PJ (2000) The adaptative mechanisms of PubMed

Rosenzweig D, Smith D, Opperdoes F, Stern S, Olafson RW, et al. (2008) Retooling PubMed

Saunders EC, Ng WW, Kloehn J, Chambers JM, Ng M, et al. (2014) Induction of a stringent metabolic response in intracellular stages of PubMed DOI PMC

Mottram JC, Coombs GH (1985) PubMed

Zangger H, Hailu A, Desponds C, Lye LF, Akopyants NS, et al. (2014) PubMed DOI PMC

Ronet C, Beverley SM, Fasel N (2011) Muco-cutaneous leishmaniasis in the New World: the ultimate subversion. Virulence 2: 547–552. 10.4161/viru.2.6.17839 PubMed DOI PMC

Hartley MA, Ronet C, Zangger H, Beverley SM, Fasel N (2012) PubMed DOI PMC

Soares MJ, Motta MC, de Souza W (1989) Bacterium-like endosymbiont and virus-like particles in the trypanosomatid

Motta MC, de Souza W, Thiry M (2003) Immunocytochemical detection of DNA and RNA in endosymbiont-bearing trypanosomatids. FEMS Microbiol Lett 221: 17–23. PubMed

Ahuja K, Arora G, Khare P, Selvapandiyan A (2015) Selective elimination of PubMed

Alvar J, Aparicio P, Aseffa A, Den Boer M, Canavate C, et al. (2008) The relationship between leishmaniasis and AIDS: the second 10 years. Clin Microbiol Rev 21: 334–359, table of contents. 10.1128/CMR.00061-07 PubMed DOI PMC

Svobodová M, Volf P, Votýpka J (2006) Experimental transmission of PubMed

Yurchenko V, Lukeš J, Xu X, Maslov DA (2006) An integrated morphological and molecular approach to a new species description in the Trypanosomatidae: the case of PubMed

Yurchenko V, Lukeš J, Jirků M, Maslov DA (2009) Selective recovery of the cultivation-prone components from mixed trypanosomatid infections: a case of several novel species isolated from Neotropical Heteroptera. Int J Syst Evol Microbiol 59: 893–909. 10.1099/ijs.0.001149-0 PubMed DOI

Huang S (2010) Statistical issues in subpopulation analysis of high content imaging data. J Comput Biol 17: 879–894. 10.1089/cmb.2009.0071 PubMed DOI

Dollet M, Sturm NR, Campbell DA (2012) The internal transcribed spacer of ribosomal RNA genes in plant trypanosomes ( PubMed DOI

Yurchenko V, Lukeš J, Tesařová M, Jirků M, Maslov DA (2008) Morphological discordance of the new trypanosomatid species phylogenetically associated with the genus PubMed

Votýpka J, Kostygov AY, Kraeva N, Grybchuk-Ieremenko A, Tesařová M, et al. (2014) PubMed DOI

Stanke M, Keller O, Gunduz I, Hayes A, Waack S, et al. (2006) AUGUSTUS: PubMed PMC

Aslett M, Aurrecoechea C, Berriman M, Brestelli J, Brunk BP, et al. (2010) TriTrypDB: a functional genomic resource for the Trypanosomatidae. Nucleic Acids Res 38: D457–462. 10.1093/nar/gkp851 PubMed DOI PMC

Schattner P, Brooks AN, Lowe TM (2005) The tRNAscan-SE, snoscan and snoGPS web servers for the detection of tRNAs and snoRNAs. Nucleic Acids Res 33: W686–689. PubMed PMC

Aurrecoechea C, Barreto A, Brestelli J, Brunk BP, Cade S, et al. (2013) EuPathDB: the eukaryotic pathogen database. Nucleic Acids Res 41: D684–691. 10.1093/nar/gks1113 PubMed DOI PMC

Li L, Stoeckert CJ Jr., Roos DS (2003) OrthoMCL: identification of ortholog groups for eukaryotic genomes. Genome Res 13: 2178–2189. PubMed PMC

Si Y, Liu P (2013) An optimal test with maximum average power while controlling FDR with application to RNA-seq data. Biometrics 69: 594–605. 10.1111/biom.12036 PubMed DOI

Gotz S, Garcia-Gomez JM, Terol J, Williams TD, Nagaraj SH, et al. (2008) High-throughput functional annotation and data mining with the Blast2GO suite. Nucleic Acids Res 36: 3420–3435. 10.1093/nar/gkn176 PubMed DOI PMC

Beiting DP, Peixoto L, Akopyants NS, Beverley SM, Wherry EJ, et al. (2014) Differential induction of TLR3-dependent innate immune signaling by closely related parasite species. PLoS One 9: e88398 10.1371/journal.pone.0088398 PubMed DOI PMC

Kelly S, Reed J, Kramer S, Ellis L, Webb H, et al. (2007) Functional genomics in PubMed PMC

Kushnir S, Gase K, Breitling R, Alexandrov K (2005) Development of an inducible protein expression system based on the protozoan host PubMed

Kraeva N, Ishemgulova A, Lukeš J, Yurchenko V (2014) Tetracycline-inducible gene expression system in PubMed

Volf P, Volfová V (2011) Establishment and maintenance of sand fly colonies. J Vector Ecol 36 Suppl 1: S1–9. PubMed

Myšková J, Votýpka J, Volf P (2008) PubMed

Rogers M, Kropf P, Choi BS, Dillon R, Podinovskaia M, et al. (2009) Proteophosophoglycans regurgitated by PubMed DOI PMC

The first RNA viruses detected in a trypanosome

Chromosome-level genome assembly of trypanosomatid parasite Lotmaria passim links chromosome duplication and divergence with infection of honey bees

Identification of diverse RNA viruses in Obscuromonas flagellates (Euglenozoa: Trypanosomatidae: Blastocrithidiinae)

Multiple and frequent trypanosomatid co-infections of insects: the Cuban case study

Evolution of RNA viruses in trypanosomatids: new insights from the analysis of Sauroleishmania

Shining the spotlight on the neglected: new high-quality genome assemblies as a gateway to understanding the evolution of Trypanosomatidae

Leishmania guyanensis M4147 as a new LRV1-bearing model parasite: Phosphatidate phosphatase 2-like protein controls cell cycle progression and intracellular lipid content

Catalase impairs Leishmania mexicana development and virulence

Genomics of Trypanosomatidae: Where We Stand and What Needs to Be Done?

Differences in mitochondrial NADH dehydrogenase activities in trypanosomatids

A New Model Trypanosomatid, Novymonas esmeraldas: Genomic Perception of Its "Candidatus Pandoraea novymonadis" Endosymbiont

Complete minicircle genome of Leptomonas pyrrhocoris reveals sources of its non-canonical mitochondrial RNA editing events

Euglenozoa: taxonomy, diversity and ecology, symbioses and viruses

Catalase and Ascorbate Peroxidase in Euglenozoan Protists

Experimental infections and co-infections with Leishmania braziliensis and Leishmania infantum in two sand fly species, Lutzomyia migonei and Lutzomyia longipalpis

The First Non-LRV RNA Virus in Leishmania

Suicidal Leishmania

If host is refractory, insistent parasite goes berserk: Trypanosomatid Blastocrithidia raabei in the dock bug Coreus marginatus

Molecular Characterization of Leishmania RNA virus 2 in Leishmaniamajor from Uzbekistan

Comparative genomics of Leishmania (Mundinia)