title: Geographical sequence variation in the Leishmania major virulence factor P46.
abstract: Cutaneous leishmaniasis as caused by Leishmania major is a zoonotic infection with wide epidemiological impact. The L. major P46 virulence gene was shown to boost the parasite's virulence and extends its range of experimental hosts. Here we show that P46 is subject to significant geographical sequence variations that may reflect the adaption to different reservoir hosts. This view is supported by the results of passage experiments using P46 variants in different experimental hosts. Conversely, loss of P46 expression leads to attenuation both in vitro and in BALB/c mice. Although part of the L. major exosomal protein payload, P46 is not required for exosome-mediated immune modulation.
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Bifeld
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Mareike
authors.initials: M
authors.lastname: Chrobak
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Zander
authors.affiliation: Institute for Microbiology, and Hygiene, Charitè University Medicine Berlin, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schleicher
authors.affiliation: Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schönian
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany. Electronic address: clos@bnitm.de.
authors.forename: Joachim
authors.initials: J
authors.lastname: Clos
mesh_terms: D000349:Africa / Q000453:epidemiology; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D055354:Exosomes / Q000469:parasitology; D054884:Host-Pathogen Interactions / Q000235:genetics*; D018320:Leishmania major / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity*; D016773:Leishmaniasis, Cutaneous / Q000453:epidemiology / Q000469:parasitology*; D008264:Macrophages / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008877:Middle East / Q000453:epidemiology; D058974:Phylogeography; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D037521:Virulence Factors
keywords: Genetics; Host adaption; Infectivity; L. major; P46