Enzymatic detoxification of O2 and NO in the human parasite, Giardia intestinalis: A mini review

Giardia intestinalis is the etiological agent of giardiasis, a common human intestinal disease with 280 million cases per year. Giardiasis is typically treated with the broad-range antibiotic metronidazole; however, the emergence of drug-resistant strains calls for the development of new anti-parasitic drugs. Very little is known regarding the molecular mechanisms adopted by Giardia to cope with the oxidative/nitrosative environmental stress, encountered by the parasite during colonization of the human intestine. Giardia is particularly sensitive to oxidative stress, as it lacks some of the most common ROS-detoxifying enzymes and it is endowed with O-2-labile key metabolic enzymes. Surprisingly, it colonizes a fairly aerobic (up to 50 mu M O-2) tract of the human gut (the upper part of the small intestine). Accordingly, survival of the parasite relies on antioxidant systems, though, as yet, the only two H2O-forming and O-2-consuming enzymes described in Giardia are NADH oxidase and flavodiiron protein (FDP). Nitric oxide (NO) is an antimicrobial agent produced, together with ROS, by the host immune system to fight pathogens. In vitro NO-stress has been reported to have cytostatic, rather than cytotoxic, effects on Giardia. This effect leads to the suggestion that Giardia is endowed with defense mechanisms against NO and, very recently, the NO-detoxifying flavohemoglobin from it has been characterized.