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The microaerophilic protozoan parasite  Giardia intestinalis , causative of one of the most common human intestinal diseases worldwide, infects the mucosa of the proximal small intestine, where it has to cope with O 2  and nitric oxide (NO). Elucidating the antioxidant defense system of this pathogen lacking catalase and other conventional antioxidant enzymes is thus important to unveil novel potential drug targets. Enzymes metabolizing O 2 , NO and superoxide anion (O 2   −• ) have been recently reported for  Giardia , but it is yet unknown how the parasite copes with H 2 O 2  and peroxynitrite (ONOO − ).  Giardia  encodes two yet uncharacterized 2-cys peroxiredoxins (Prxs),  Gi Prx1a and  Gi Prx1b. Peroxiredoxins are peroxidases implicated in virulence and drug resistance in several parasitic protozoa, able to protect from nitroxidative stress and repair oxidatively damaged molecules.  Gi Prx1a and a truncated form of  Gi Prx1b (delta Gi Prx1b) were expressed in  Escherichia coli , purified and functionally characterized. Both Prxs effectively metabolize H 2 O 2  and alkyl-hydroperoxides (cumyl- and tert-butyl-hydroperoxide) in the presence of NADPH and  E. coli  thioredoxin reductase/thioredoxin as the reducing system. Stopped-flow experiments show that both proteins in the reduced state react with ONOO −  rapidly ( k  = 4×10 5  M −1  s −1  and 2×10 5  M −1  s −1  at 4°C, for  Gi Prx1a and delta Gi Prx1b, respectively). Consistent with a protective role against oxidative stress, expression of  Gi Prx1a (but not delta Gi Prx1b) is induced in parasitic cells exposed to air O 2  for 24 h. Based on these results,  Gi Prx1a and delta Gi Prx1b are suggested to play an important role in the antioxidant defense of  Giardia , possibly contributing to pathogenesis.

Functional Characterization of Peroxiredoxins from the Human Protozoan Parasite Giardia intestinalis