Abstract
ABSTRACTLeishmania 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.
Highlights
The obligate intracellular protozoan parasites of the genus Leishmania are causative for the various forms of Leishmaniasis
We demonstrated that the expression of this newly identified sHSP is induced during stage conversion, is involved in the L. donovani adaption to specific stresses and is essential for the infectivity in a murine macrophage model
Kinetoplastida possess atypical sHSPs Because virtually nothing was known about the roles and functions of a-crystallin-domain-containing proteins (ACDPs) in kinetoplastid protozoa, we first performed a search of the Tritryp database, using the human P23 co-chaperone sequence and the BLAST algorithm
Summary
The obligate intracellular protozoan parasites of the genus Leishmania are causative for the various forms of Leishmaniasis. The clinical manifestations range from selfhealing skin lesions (cutaneous leishmaniasis) to lethal, generalised infections of the reticulo-endothelial system (visceral leishmaniasis). The infections are found on four continents with an estimated annual incidence of between 900,000 and 1.8 million (Alvar et al, 2012). Leishmania spp. undergo two life cycle stages – the extracellular promastigote stage in the insect vector, and the intracellular amastigote form, in the phagosomes of infected macrophages. The parasites colonise two very diverse environments in the course of their life cycle. The transmission of Leishmania spp. from a poikilothermic
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