Deletion of the Trypanosoma brucei superoxide dismutase gene sodb1 increases sensitivity to nifurtimox and benznidazole.
نویسندگان
چکیده
It has been more than 25 years since it was first reported that nifurtimox and benznidazole promote superoxide production in trypanosomes. However, there has been no direct evidence of an association between the drug-induced free radicals and trypanocidal activity. Here, we identify a superoxide dismutase required to protect Trypanosoma brucei from drug-generated superoxide.
منابع مشابه
A mechanism for cross-resistance to nifurtimox and benznidazole in trypanosomes.
Nifurtimox and benznidazole are the front-line drugs used to treat Chagas disease, the most important parasitic infection in the Americas. These agents function as prodrugs and must be activated within the parasite to have trypanocidal effects. Despite >40 years of research, the mechanism(s) of action and resistance have remained elusive. Here, we report that in trypanosomes, both drugs are act...
متن کاملDeletion of the Trypanosoma brucei superoxide dismutase gene
25 It is >25 years since it was first reported that nifurtimox and benznidazole 26 promote superoxide production in trypanosomes. However, there has been no 27 direct evidence of an association between the drug-induced free radicals and 28 trypanocidal activity. Here, we identify a superoxide dismutase required to 29 protect Trypanosoma brucei from drug-generated superoxide. 30 31 32 33 Parasit...
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Nifurtimox (Nfx) and benznidazole (Bz) are the current drugs used for the treatment of Chagas disease. The mechanisms of action and resistance to these drugs in this parasite are poorly known. Prostaglandin F2α synthase or old yellow enzyme (OYE), an NAD(P)H flavin oxidoreductase, has been involved in the activation pathway of other trypanocidal drugs such as Nfx; however, its role in the mecha...
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To be effective, therapeutic compounds must typically enter target cells and, in some cases, must be concentrated or modified. Thus, uptake and activation mechanisms often form the basis of selectivity against infectious agents. Loss-of-function screens can be used to identify proteins involved in drug uptake and metabolism and may also identify clinically relevant potential resistance mechanis...
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عنوان ژورنال:
- Antimicrobial agents and chemotherapy
دوره 51 2 شماره
صفحات -
تاریخ انتشار 2007