Leishmania major glycosylation mutants require phosphoglycans (lpg2-) but not lipophosphoglycan (lpg1-) for survival in permissive sand fly vectors

. 2010 Jan 12 ; 4 (1) : e580. [epub] 20100112

Jazyk angličtina Země Spojené státy americké Médium electronic

Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid20084096

Grantová podpora
Wellcome Trust - United Kingdom
078937 Wellcome Trust - United Kingdom
R01 AI031078 NIAID NIH HHS - United States
AI31078 NIAID NIH HHS - United States

BACKGROUND: Sand fly species able to support the survival of the protozoan parasite Leishmania have been classified as permissive or specific, based upon their ability to support a wide or limited range of strains and/or species. Studies of a limited number of fly/parasite species combinations have implicated parasite surface molecules in this process and here we provide further evidence in support of this proposal. We investigated the role of lipophosphoglycan (LPG) and other phosphoglycans (PGs) in sand fly survival, using Leishmania major mutants deficient in LPG (lpg1(-)), and the phosphoglycan (PG)-deficient mutant lpg2(-). The sand fly species used were the permissive species Phlebotomus perniciosus and P. argentipes, and the specific vector P. duboscqi, a species resistant to L. infantum development. PRINCIPAL FINDINGS: The lpg2(-) mutants did not survive well in any of the three sand fly species, suggesting that phosphoglycans and/or other LPG2-dependent molecules are required for parasite development. In vitro, all three L. major lines were equally resistant to proteolytic activity of bovine trypsin, suggesting that sand fly-specific hydrolytic proteases or other factors are the reason for the early lpg2(-) parasite killing. The lpg1(-) mutants developed late-stage infections in two permissive species, P. perniciosus and P. argentipes, where their infection rates and intensities of infections were comparable to the wild type (WT) parasites. In contrast, in P. duboscqi the lpg1(-) mutants developed significantly worse than the WT parasites. CONCLUSIONS: In combination with previous studies, the data establish clearly that LPG is not required for Leishmania survival in permissive species P. perniciosus and P. argentipes but plays an important role in the specific vector P. duboscqi. With regard to PGs other than LPG, the data prove the importance of LPG2-related molecules for survival of L. major in the three sand fly species tested.

Zobrazit více v PubMed

Volf P, Myskova J. Sand flies and Leishmania: specific versus permissive vectors. Trends Parasitol. 2007;23:91–92. PubMed PMC

Kamhawi S. Phlebotomine sand flies and Leishmania parasites: friends or foes? Trends Parasitol. 2006;22:439–445. PubMed

Ilg T. Proteophosphoglycans of Leishmania. Parasitol Today. 2000;16:489–497. PubMed

Sacks DL, Modi G, Rowton E, Spath G, Epstein L, et al. The role of phosphoglycans in Leishmania-sand fly interactions. Proc Natl Acad Sci USA. 2000;97:406–411. PubMed PMC

Turco SJ, Spath GF, Beverley SM. Is lipophosphoglycan a virulence factor? A surprising diversity between Leishmania species. Trends Parasitol. 2001;17:223–226. PubMed

Beverley SM, Turco SJ. Lipophosphoglycan (LPG) and the identification of virulence genes in the protozoan parasite Leishmania. Trends Microbiol. 1998;6:35–40. PubMed

Spath GF, Epstein L, Leader B, Singer SM, Avila HA, et al. Lipophosphoglycan is a virulence factor distinct from related glycoconjugates in the protozoan parasite leishmania major. Proc Natl Acad Sci USA. 2000;97:9258–9263. PubMed PMC

Descoteaux A, Luo Y, Turco SJ, Beverley SM. A specialized pathway affecting virulence glycoconjugates of Leishmania. Science. 1995;269:1869–1872. PubMed

Spath GF, Lye LF, Segawa H, Sacks DL, Turco SJ, et al. Persistence without pathology in phosphoglycan-deficient Leishmania major. Science. 2003;301:1241–1243. PubMed

Capul AA, Hickerson S, Barron T, Turco SJ, Beverley SM. Comparisons of mutants lacking the Golgi UDP-galactose or GDP-mannose transporters establish that phosphoglycans are important for promastigote but not amastigote virulence in Leishmania major. Infect Immun. 2007;75:4629–4637. PubMed PMC

Uzonna JE, Spath GF, Beverley SM, Scott P. Vaccination with phosphoglycan-deficient Leishmania major protects highly susceptible mice from virulent challenge without inducing a strong Th1 response. J Immunol. 2004;172:3793–3797. PubMed

Capul AA, Barron T, Dobson DE, Turco SJ, Beverley SM. Two functionally divergent UDP-Gal nucleotide sugar transporters participate in phosphoglycan synthesis in Leishmania major. J Biol Chem. 2007;282:14006–14017. PubMed PMC

Spath GF, Garraway LA, Turco SJ, Beverley SM. The role(s) of lipophosphoglycan (LPG) in the establishment of Leishmania major infections in mammalian hosts. Proc Natl Acad Sci USA. 2003;100:9536–9541. PubMed PMC

Ilg T. Lipophosphoglycan of the protozoan parasite Leishmania: stage- and species-specific importance for colonization of the sandfly vector, transmission and virulence to mammals. Med Microbiol Immunol. 2001;190:13–17. PubMed

Kamhawi S, Ramalho-Ortigao M, Pham VM, Kumar S, Lawyer PG, et al. A role for insect galectins in parasite survival. Cell. 2004;119:329–341. PubMed

Killick-Kendrick R, Killick-Kendrick M, Tang Y. Anthroponotic cutaneous leishmaniasis in Kabul, Afghanistan: The low susceptibility of Phlebotomus papatasi Leishmania tropica. Trans R Soc Trop Med Hyg. 1994;88:252–253. PubMed

Heyneman D. 12. Comparison of experimental Leishmania donovani infection. Am J Trop Med Hyg. 1963;12:725–740.

Walters LI, Irons KP, Modi GB, Tesh RB. Refractory barriers in the sandfly Phlebotomus papatasi (Diptera: Psychodidae) to infection with Leishmania panamensis. Am J Trop Med Hyg. 1992;46:211–228. PubMed

Pimenta PFP, Saraiva EMB, Rowton E, Modi GB, Garraway LA, et al. Evidence that the vectorial competence of phlebotomine sand flies for different species of Leishmania is controlled by structural polymorphisms in the surface lipophosphoglycan. Proc Natl Acad Sci USA. 1994;91:9155–9159. PubMed PMC

Myskova J, Svobodova M, Beverley SM, Volf P. A lipophosphoglycan-independent development of Leishmania in permissive sand flies. Microbes Infect. 2007;9:317–324. PubMed PMC

Lawyer PG, Githure JI, Anjili CO, Olobo JO, Koech DK, et al. Experimental transmission of Leishmania major vervet monkeys (Cercopithecus aethiops) by bites of Phlebotomus duboscqi (Diptera: Psychodidae). Trans R Soc Trop Med Hyg. 1990;84:229–232. PubMed

Beach R, Kiilu G, Hendricks L, Oster C, Leeuwenburg J. Cutaneous leishmaniasis in Kenya - transmission of Leishmania major to man by the bite of a naturally infected Phlebotomus duboscqi. Trans R Soc Trop Med Hyg. 1984;78:747–751. PubMed

Lane RP, Pile MM, Amerasinghe FP. Anthropophagy and Aggregation Behavior of the Sandfly Phlebotomus-Argentipes in Sri-Lanka. Med Vet Entomol. 1990;4:79–88. PubMed

Shortt HE, Smith ROA, Swaminath CS, Krishnan KV. Transmission of kala-azar by the bite of Phlebotomus argentipes. Ind J Med Res. 1931;18:1373–1375.

Marchand M, Daoud S, Titus RG, Louis J, Boon T. Variants with reduced virulence derived from Leishmania major after mutagen treatment. Parasite Immunol. 1987;9:81–92. PubMed

Benkova I, Volf P. Effect of temperature on metabolism of Phlebotomus papatasi (Diptera : Psychodidae). Journal Med Entomol. 2007;44:150–154. PubMed

Cihakova J, Volf P. Development of different Leishmania major strains in the vector sandflies Phlebotomus papatasi and P-duboscqi. Ann Trop Med Parasitol. 1997;91:267–279. PubMed

Volf P, Killick-Kendrick R. Post-engorgement dynamics of haemagglutination activity in the midgut of phlebotomine sandflies. Med Vet Entomol. 1996;10:247–250. PubMed

Rogers ME, Ilg T, Nikolaev AV, Ferguson MAJ, Bates PA. Transmission of cutaneous leishmaniasis by sand flies is enhanced by regurgitation of fPPG. Nature. 2004;430:463–467. PubMed PMC

Ryan KA, Garraway LA, Descoteaux A, Turco SJ, Beverley SM. Isolation of virulence genes directing surface glycosyl-phosphatidylinositol synthesis by functional complementation of Leishmania. Proc Natl Acad Sci USA. 1993;90:8609–8613. PubMed PMC

King DL, Turco SJ. A ricin agglutinin-resistant clone of Leishmania donovani deficient in lipophosphoglycan. Mol Biochem Parasitol. 1988;28:285–294. PubMed

Boulanger N, Lowenberger C, Volf P, Ursic R, Sigutova L, et al. Characterization of a defensin from the sand fly Phlebotomus duboscqi induced by challenge with bacteria or the protozoan parasite Leishmania major. Infect Immun. 2004;72:7140–7146. PubMed PMC

Pimenta PFP, Modi GB, Pereira ST, Shahabuddin M, Sacks DL. A novel role for the peritrophic matrix in protecting Leishmania from the hydrolytic activities of the sand fly midgut. Parasitology. 1997;115:359–369. PubMed

Shakarian AM, Dwyer DM. Structurally conserved soluble acid phosphatases are synthesized and released by Leishmania major promastigotes. Exp Parasitol. 2000;95:79–84. PubMed

Ramalho-Ortigao M, Jochim RC, Anderson JM, Lawyer PG, Pham VM, et al. Exploring the midgut transcriptome of Phlebotomus papatasi: comparative analysis of expression profiles of sugar-fed, blood-fed and Leishmania major-infected sandflies. BMC Genomics. 2007;8:300. PubMed PMC

Jochim RC, Teixeira CR, Laughinghouse A, Mu JB, Oliveira F, et al. The midgut transcriptome of Lutzomyia longipalpis: comparative analysis of cDNA libraries from sugar-fed, blood-fed, post-digested and Leishmania infantum chagasi-infected sand flies. BMC Genomics. 2008;9:15. PubMed PMC

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