Nejvíce citovaný článek - PubMed ID 3762526
BACKGROUND: Leishmania parasites are transmitted by phlebotomine sand flies and a crucial step in their life-cycle is the binding to the sand fly midgut. Laboratory studies on sand fly competence to Leishmania parasites suggest that the sand flies fall into two groups: several species are termed "specific/restricted" vectors that support the development of one Leishmania species only, while the others belong to so-called "permissive" vectors susceptible to a wide range of Leishmania species. In a previous study we revealed a correlation between specificity vs permissivity of the vector and glycosylation of its midgut proteins. Lutzomyia longipalpis and other four permissive species tested possessed O-linked glycoproteins whereas none were detected in three specific vectors examined. RESULTS: We used a combination of biochemical, molecular and parasitological approaches to characterize biochemical and biological properties of O-linked glycoprotein of Lu. longipalpis. Lectin blotting and mass spectrometry revealed that this molecule with an apparent molecular weight about 45-50 kDa corresponds to a putative 19 kDa protein with unknown function detected in a midgut cDNA library of Lu. longipalpis. We produced a recombinant glycoprotein rLuloG with molecular weight around 45 kDa. Anti-rLuloG antibodies localize the native glycoprotein on epithelial midgut surface of Lu. longipalpis. Although we could not prove involvement of LuloG in Leishmania attachment by blocking the native protein with anti-rLuloG during sand fly infections, we demonstrated strong binding of rLuloG to whole surface of Leishmania promastigotes. CONCLUSIONS: We characterized a novel O-glycoprotein from sand fly Lutzomyia longipalpis. It has mucin-like properties and is localized on the luminal side of the midgut epithelium. Recombinant form of the protein binds to Leishmania parasites in vitro. We propose a role of this molecule in Leishmania attachment to sand fly midgut.
- Klíčová slova
- Glycoprotein, Leishmania, Lipophosphoglycan, Phlebotomine sand flies,
- MeSH
- glykokonjugáty genetika metabolismus MeSH
- hmyz - vektory metabolismus parazitologie MeSH
- hmyzí proteiny genetika metabolismus MeSH
- Leishmania fyziologie MeSH
- muciny genetika metabolismus MeSH
- Psychodidae genetika metabolismus parazitologie MeSH
- trávicí systém metabolismus parazitologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- glykokonjugáty MeSH
- hmyzí proteiny MeSH
- muciny MeSH
Leishmaniases are serious parasitic diseases the etiological organisms of which are transmitted by insect vectors, phlebotominae sand flies. Two sand fly species, Phlebotomus papatasi and P. sergenti, display remarkable specificity for Leishmania parasites they transmit in nature, but many others are broadly permissive to the development of different Leishmania species. Previous studies have suggested that in 'specific' vectors the successful parasite development is mediated by parasite surface glycoconjugates and sand fly lectins, however we show here that interactions involving 'permissive' sand flies utilize another molecules. We did find that the abundant surface glycoconjugate lipophosphoglycan, essential for attachment of Leishmania major in the specific vector P. papatasi, was not required for parasite adherence or survival in the permissive vectors P. arabicus and Lutzomyia longipalpis. Attachment in several permissive sand fly species instead correlated with the presence of midgut glycoproteins bearing terminal N-acetyl-galactosamine and with the occurrence of a lectin-like activity on Leishmania surface. This new binding modality has important implications for parasite transmission and evolution. It may contribute to the successful spreading of Leishmania due to their adaptation into new vectors, namely transmission of L. infantum by Lutzomyia longipalpis; this event led to the establishment of L. infantum/chagasi in Latin America.
- MeSH
- acetylgalaktosamin metabolismus MeSH
- glykoproteiny chemie metabolismus MeSH
- glykosfingolipidy metabolismus MeSH
- hmyz - vektory MeSH
- Leishmania infantum fyziologie MeSH
- Leishmania klasifikace růst a vývoj MeSH
- Phlebotomus klasifikace parazitologie MeSH
- Psychodidae klasifikace parazitologie MeSH
- trávicí systém parazitologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- acetylgalaktosamin MeSH
- glykoproteiny MeSH
- glykosfingolipidy MeSH
- lipophosphonoglycan MeSH Prohlížeč
Transmission of Leishmania tropica was studied in 2 adjacent foci in Israel where vector populations differ. Only Phlebotomus sergenti was found infected with L. tropica in the southern focus; P. arabicus was the main vector in the northern focus. Rock hyraxes (Procavia capensis) were incriminated as reservoir hosts in both foci. L. tropica strains from the northern focus isolated from sand flies, cutaneous leishmaniasis cases, and rock hyraxes were antigenically similar to L. major, and strains from the southern focus were typically L. tropica. Laboratory studies showed that P. arabicus is a competent vector of L. tropica, and P. sergenti is essentially refractory to L. tropica from the northern focus. Susceptibility of P. arabicus may be mediated by O glycoproteins on the luminal surface of its midgut. The 2 foci differ with respect to parasites and vectors, but increasing peridomestic rock hyrax populations are probably responsible for emergence of cutaneous leishmaniasis in both foci.
- MeSH
- damani parazitologie MeSH
- fluorescenční protilátková technika nepřímá MeSH
- hmyz - vektory parazitologie MeSH
- Leishmania tropica genetika izolace a purifikace MeSH
- leishmanióza kožní epidemiologie parazitologie přenos MeSH
- mezerníky ribozomální DNA chemie genetika MeSH
- polymerázová řetězová reakce MeSH
- protozoální DNA chemie genetika MeSH
- Psychodidae parazitologie MeSH
- zdroje nemoci veterinární MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Izrael epidemiologie MeSH
- Názvy látek
- mezerníky ribozomální DNA MeSH
- protozoální DNA MeSH