How does the human parasite Giardia intestinalis cope with nitrosative stress?

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The anaerobic protist Giardia intestinalis, the most common protozoan intestinal parasite worldwide, infects the fairly oxygenated human small intestine, where it has to cope with O2 and NO stress. Based on genomic studies, although lacking common antioxidant enzymes (like superoxide dismutase and catalase), Giardia is the only pathogenic protist as yet identified encoding a flavohemoglobin (flavoHb) and among the very few eukaryotes encoding a superoxide reductase (SOR) and a flavodiiron protein (FDP). While the FDP was suggested to be involved in O2 detoxification, we found that the recombinant Giardia flavoHb aerobically metabolizes NO with high efficacy (Vmax = 116 ± 10 s−1 at 1 μM NO, K M, O 2 = 22 ± 7 μ M , T = 37 °C). The parasitic cells express this microbial globin at low levels and, accordingly, metabolize NO with low efficacy. In response to nitrosative stress, however, flavoHb expression is enhanced and the parasite thereby becomes able to aerobically metabolize NO efficiently. In collaboration with M. Teixeira and L.M. Saraiva (New University of Lisbon, Portugal) and D.E. Cabelli (Brookhaven National Laboratory, New York, USA), more recently the recombinant Giardia SOR was also purified and characterized. The protein, immunodetected in Giardia cells, shows negligible superoxide dismutase activity, but in the reduced state is highly reactive with superoxide anion, as shown by pulse radiolysis and stopped-flow spectrophotometry. It is suggested that flavoHb and SOR in vivo contribute to protect Giardia from nitrosative stress, thus promoting parasite pathogenicity.