AI Article Synopsis
- Protozoan parasites like Leishmania switch life stages to adapt to their hosts, with this process influenced by environmental stresses and chaperone proteins.
- The study found that null mutants lacking cyclophilin 40 (cyp40-/-) showed virulence defects but did not struggle with oxidative or hydrolytic stress inside macrophages.
- Further analysis indicated that cyp40-/- mutants have increased stress proteins and vesicle accumulation, suggesting they face significant internal stress that affects their survival during infection.
Article Abstract
Protozoan parasites of the genus Leishmania adapt to their arthropod and vertebrate hosts through the development of defined life cycle stages. Stage differentiation is triggered by environmental stress factors and has been linked to parasite chaperone activities. Using a null mutant approach we previously revealed important, nonredundant functions of the cochaperone cyclophilin 40 in L. donovani-infected macrophages. Here, we characterized in more detail the virulence defect of cyp40-/- null mutants. In vitro viability assays, infection tests using macrophages, and mixed infection experiments ruled out a defect of cyp40-/- parasites in resistance to oxidative and hydrolytic stresses encountered inside the host cell phagolysosome. Investigation of the CyP40-dependent proteome by quantitative 2D-DiGE analysis revealed up regulation of various stress proteins in the null mutant, presumably a response to compensate for the lack of CyP40. Applying transmission electron microscopy we showed accumulation of vesicular structures in the flagellar pocket of cyp40-/- parasites that we related to a significant increase in exosome production, a phenomenon previously linked to the parasite stress response. Together these data suggest that cyp40-/- parasites experience important intrinsic homeostatic stress that likely abrogates parasite viability during intracellular infection.
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| http://dx.doi.org/10.1111/jeu.12329 | DOI Listing |
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