Heat Shock Proteins in Leishmania Parasites
Parasites of the genus Leishmania (Class Kinetoplastea, Order Trypanosomatida, Family Trypanosomatidae) cause a variety of clinical syndromes from localised, self-healing skin lesions to generalised, progressive and lethal systemic infections. They are ea
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Abstract Introduction Parasites of the genus Leishmania (Class Kinetoplastea, Order Trypanosomatida, Family Trypanosomatidae) cause a variety of clinical syndromes from localised, self-healing skin lesions to generalised, progressive and lethal systemic infections. They are early branching eukaryotes that lack gene-specific transcription regulation, RNA polymerase II promoters and trans acting transcription factors, and rely instead mostly on regulated translation and gene copy number variations for short- and long-term gene expression control. Methods The authors reviewed the literature about the roles and functions of heat shock proteins in Leishmania spp. Results Leishmania spp. possess a full complement of molecular chaperones, which play crucial roles in both parts of the biphasic, parasitic life cycle, having an impact on the temperature-induced differentiation from the insect stage to the mammalian stage, but also on the intracellular survival within mammalian hosts. They are part of the signal transduction pathways regulating life cycle stage conversion and subject to modulation by protein kinases. Heat shock proteins are also implicated in the immune response to Leishmania infections, the modulation of the host’s immune system and in the resistance of the parasites against chemotherapy. Conclusions Heat shock proteins play pivotal roles in the control of the parasitic life cycle and in the survival within the mammalian hosts.
Constanze Kröber-Boncardo, Janne Grünebast and Joachim Clos contributed equally with all other contributors. C. Kröber-Boncardo · J. Grünebast · J. Clos (*) Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany e-mail: [email protected] © Springer Nature Switzerland AG 2020 A. A. A. Asea, P. Kaur (eds.), Heat Shock Proteins, https://doi.org/10.1007/7515_2020_27
C. Kröber-Boncardo et al.
Keywords Amastigote · Exosomes · HSP100 · HSP23 · HSP90 · Leishmania
1 Introduction 1.1
Gene Regulation in Leishmania spp.: A Farewell to Promoters
The genus Leishmania is part of the family Trypanosomatidae, Order Trypanosomatida, and part of the early branching, eukaryotic phylum Euglenozoa. Due to some peculiar biochemical features, they garnered the attention of molecular biologists early on. Processes such as trans-splicing and RNA editing were first described in Trypanosoma brucei and are found in all the kinetoplastida [1]. Also common to the members of this order is a lack of gene-specific transcription regulation [2]. There are no gene promoters in the strict sense in Leishmania, and the genome projects of numerous Trypanosomatida species (e.g. L. major, L. infantum, L. braziliensis, Trypanosoma brucei, and Trypanosoma cruzi) did not yield any genes for common trans-regulatory factors of transcription. Rather, large chromosomal regions are transcribed as multicistronic precursor RNA which is subject to trans-splicing coupled to polyadenylation to create mature, monocistronic mRNA [3]. This mode of transcription alone effectively precludes gene-specific transcription control. Recent wor
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