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The loss of virulence of histone H 1 overexpressing L eishmania donovani parasites is directly associated with a reduction of HSP 83 rate of translation
Author(s) -
Alexandratos Alexandros,
Clos Joachim,
Samiotaki Martina,
Efstathiou Antonia,
Panayotou George,
Soteriadou Ketty,
Smirlis Despina
Publication year - 2013
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12240
Subject(s) - biology , translation (biology) , virulence , reduction (mathematics) , genetics , gene , messenger rna , geometry , mathematics
Summary Overexpression of L eishmania histone H 1 ( LeishH 1) was previously found to cause a promastigote‐to‐amastigote differentiation handicap, deregulation of cell‐cycle progression, and loss of parasite infectivity. The aim of this study was to identify changes in the proteome of LeishH 1 overexpressing parasites associated with the avirulent phenotype observed. 2 D ‐gel electrophoresis analysis revealed only a small protein subset of differentially expressed proteins in the LeishH1 overexpressing promastigotes. Among these was the chaperone HSP 83, known for its protective role in L eishmania drug‐induced apoptosis, which displayed lower translational rates. To investigate if the lower expression levels of HSP 83 are associated with the differentiation handicap, we assayed the thermostability of parasites by subjecting them to heat‐shock (25°C→37°C), a natural stress‐factor occurring during stage differentiation. Heat‐shock promoted apoptosis to a greater extent in the LeishH 1 overexpressing parasites. Interestingly, these parasites were not only more sensitive to heat‐shock but also to drug‐induced [ Sb ( III )] cell‐death. In addition, the restoration of HSP 83 levels re‐established drug resistance, and restored infectivity to LeishH 1 overexpressing parasites in the murine J 774 macrophage model. Overall, this study suggests that LeishH 1 levels are critical for the parasite's stress‐induced adaptation within the mammalian host, and highlights the cross‐talk between pathways involved in drug resistance, apoptosis and virulence.