title: A small heat shock protein is essential for thermotolerance and intracellular survival of Leishmania donovani.
abstract: Leishmania parasites must survive and proliferate in two vastly different environments - the guts of poikilothermic sandflies and the antigen-presenting cells of homeothermic mammals. The change of temperature during the transmission from sandflies to mammals is both a key trigger for the progression of their life cycle and for elevated synthesis of heat shock proteins, which have been implicated in their survival at higher temperatures. Although the functions of the main heat shock protein families in the Leishmania life cycle have been studied, nothing is known about the roles played by small heat shock proteins. Here, we present the first evidence for the pivotal role played by the Leishmania donovani 23-kDa heat shock protein (which we called HSP23), which is expressed preferentially during the mammalian stage where it assumes a perinuclear localisation. Loss of HSP23 causes increased sensitivity to chemical stressors and renders L. donovani non-viable at 37°C. Consequently, HSP23-null mutants are non-infectious to primary macrophages in vitro. All phenotypic effects could be abrogated by the introduction of a functional HSP23 transgene into the null mutant, confirming the specificity of the mutant phenotype. Thus, HSP23 expression is a prerequisite for L. donovani survival at mammalian host temperatures and a crucial virulence factor.
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, 20259 Hamburg, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Hombach
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, 20259 Hamburg, Germany.
authors.forename: Gabi
authors.initials: G
authors.lastname: Ommen
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, 20259 Hamburg, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: MacDonald
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, 20259 Hamburg, Germany clos@bnitm.de.
authors.forename: Joachim
authors.initials: J
authors.lastname: Clos
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D050888:Heat-Shock Proteins, Small / Q000235:genetics / Q000378:metabolism*; D007893:Leishmania donovani / Q000378:metabolism* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D013696:Temperature
chemical_list: D050888:Heat-Shock Proteins, Small; D015800:Protozoan Proteins
keywords: Alpha-crystallin; HSP23; Infectivity; Leishmania; Small heat shock protein; Stress tolerance