3 years ago

Leishmania donovani Tryparedoxin Peroxidases: functional involvement during infection and drug treatment.

Chandrima Shaha, Sanchita Das, Sagnik Giri, Shyam Sundar
The parasite Leishmania donovani causes visceral leishmaniasis, a potentially fatal disease. These parasites survive within mammalian macrophages and express a unique set of enzymes, the tryparedoxin peroxidases for their defense against oxidative stress generated by the host. In this study, we demonstrate a differential role of two distinct enzymes, the mitochondrial (mTXNPx) and the cytosolic tryparedoxin peroxidase (cTXNPx) in defending the parasites against mitochondrial and exogenous oxidative stress during infection and drug treatment. Our findings indicate a comparatively higher increase in cTXNPx expression in response to exogenous oxidative stress and a relatively higher elevation of mTXNPx expression in response to mitochondrial or endogenous stress created by respiratory chain complex inhibitors. Overexpression of cTXNPx in the Leishmania show improved protection to exogenous stress and enhanced protection to mitochondrial stress in parasites overexpressing mTXNPx. Further, parasites overexpressing cTXNPx infect host cells with increased efficiency at early hours of infection as compared to control parasites or parasites overexpressing mTXNPx. The mTXNPx overexpressing parasites sustain higher infection at later hours. Higher mTXNPx expression occurred in wild type parasites on exposure to miltefosine while treatment with antimony elevated cTXNPx expression. Parasites resistant to miltefosine or antimony demonstrated increased expression of mTXNPx as well as cTXNPx. In summary, this study provides evidence of distinct role of the two enzymes defined by virtue of their localization during infection and drug treatment.

Publisher URL: http://doi.org/10.1128/AAC.00806-17

DOI: 10.1128/AAC.00806-17

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.