Geographical sequence variation in the Leishmania major virulence factor P46

Infect Genet Evol. 2015 Mar:30:195-205. doi: 10.1016/j.meegid.2014.12.029. Epub 2014 Dec 31.

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.

Keywords: Genetics; Host adaption; Infectivity; L. major; P46.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Africa / epidemiology
  • Animals
  • Cells, Cultured
  • Disease Models, Animal
  • Exosomes / parasitology
  • Host-Pathogen Interactions / genetics*
  • Leishmania major / classification
  • Leishmania major / genetics*
  • Leishmania major / pathogenicity*
  • Leishmaniasis, Cutaneous / epidemiology
  • Leishmaniasis, Cutaneous / parasitology*
  • Macrophages / parasitology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Middle East / epidemiology
  • Phylogeography
  • Virulence Factors / genetics*

Substances

  • Virulence Factors