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

Abstract

<i>Giardia intestinalis </i>is the etiological agent of <i>giardiasis</i>, a common human intestinal disease with 280 million cases per year. <i>G</i><i>iardiasis</i> 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 <i>Giardia</i> to cope with the oxidative/nitrosative environmental stress, encountered by the parasite during colonization of the human intestine. <i>Giardia</i> is particularly sensitive to oxidative stress, as it lacks some of the most common ROS-detoxifying enzymes and it is endowed with O₂-labile key metabolic enzymes. Surprisingly, it colonizes a fairly aerobic (up to 50 <img src='/image/spc_char/micro.gif' border=0> <i>M</i> O₂) 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 O₂-consuming enzymes described in <i>Giardia</i> 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. <i>In vitro</i> NO-stress has been reported to have cytostatic, rather than cytotoxic, effects on <i>Giardia</i>. This effect leads to the suggestion that <i>Giardia</i> is endowed with defense mechanisms against NO and, very recently, the NO-detoxifying flavohemoglobin from it has been characterized.