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endoplasmic reticulum. Under nitrosative stress conditions, E. histolytica
expresses a number of genes related to membrane traffic, extreme stress
responses, anaerobic energy production and cysteine metabolism ( Santi-
Rocca et al., 2012 ). Nevertheless, NO detoxification mechanisms in this
parasite have not been identified. The genome of this parasite lacks
globin-like sequences; this might be related to the high susceptibility of
the protozoan to NO. Interestingly, E. histolytica trophozoites produce
NO in culture, and the activity of NO synthase together with recognition
of proteins by specific antibodies against NOS leads to the suggestion that
NO is produced as a pathogenicity factor during invasive amebiasis
( Hernandez-Campos et al., 2003 ). The absence of NO detoxification mech-
anisms such as globins in an organism that produces NO may appear logical
and consistent with the picture emerging for certain fungi, as discussed
above. However, how this organism copes with the toxicity of exogenous
and endogenous NO during invasion and pathogenesis is a challenging ques-
tion. Genomic analyses of E. histolytica and Giardia intestinalis have revealed
the existence of orthologues of the flavorubredoxin system ( nor genes)
( Andersson et al., 2003 )of E. coli , which represents the main NO detoxifi-
cation mechanism under anaerobic conditions ( Gardner & Gardner, 2002 ).
However, the expression and function of these parasitic putative proteins
have not been investigated.
T. vaginalis (Supplementary Table S1 at http://www.elsevierdirect.com/
companions/9780124076938 ) is a flagellated microaerophilic parasite that
causes a range of clinical manifestations from asymptomatic infection to
severe and extensive damage of the vaginal epithelium. An increased risk
of developing invasive cervical cancer is associated with Trichomoniasis
( Yap et al., 1995 ). Chronic infection by T. vaginalis is common and implies
the survival of the parasite despite the host's defence mechanisms. Even
though this parasite lacks haemoglobins, consumption of NO in oxygen-
limited conditions has been reported and a flavorubredoxin (NorV) homo-
logue has been identified by immunoblotting using E. coli anti-NorV anti-
bodies. This suggests that the reduction of NO to N 2 O may act as a
detoxification mechanism, independently of any globin ( Sarti et al., 2004 ).
Interestingly, in T. vaginalis , the arginine deaminase produces ammonia from
the conversion of arginine to citrulline in anaerobic conditions ( Yarlett,
Martinez, Goldberg, Kramer, & Porter, 2000 ), but in aerobic conditions,
NO rather than ammonia is produced in an NOS-dependent reaction
( Harris, Goldberg, Biagini, & Lloyd, 2006 ).
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