Biology Reference
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conditions, as in the macrophagic environment where
M. leprae
is faced
with H
2
O
2
(
Ascenzi, Bolognesi, & Visca, 2007; Ascenzi & Visca, 2008;
Visca, Fabozzi, Milani, et al., 2002
), the rapid formation of 2/2HbO
d
Fe
(IV)
]
O occurs, which in turn facilitates NO scavenging, leading to the
formation of haem-Fe(III) and NO
2
. In turn, NO acts as antioxidant of
2/2HbO
d
Fe(IV)
]
O, which could be responsible for the oxidative dam-
age of the mycobacterium. This reaction does not require partner redox
enzymes, since the haem-protein oscillates between the haem-Fe(III) and
haem-Fe(IV)
]
O forms, being helped by NO in maintaining an efficient
H
2
O
2
reduction rate. In this framework, it can be understood why
M. leprae
2/2HbO
d
Fe(III) does not require a reductase system(s), which
indeed has not been identified yet in this elusive mycobacterium
(
Ascenzi, Bolognesi, & Visca, 2007; Ascenzi & Visca, 2008
). The catalytic
parameters for NO scavenging by haem-Fe(II)
d
O
2
and haem-Fe(IV)
]
O
are similar and high enough, suggesting that both reactions could take place
in vivo
(
Ascenzi et al., 2008; Ascenzi & Visca, 2008
).
The H
2
O
2
-induced
M. leprae
2/2HbO
d
Fe(IV)
]
O formation could be
relevant for
M. leprae
survival
in vivo
in the presence not only of NO and
NO
2
but also of peroxynitrite (
Ascenzi, De Marinis, Visca, Ciaccio, &
Coletta, 2009
). The formation of peroxynitrite can in fact result from a sec-
ondary reaction of NO and the superoxide radical, which is concomitantly
produced by activated macrophages. Then, peroxynitrite could rapidly react
with CO
2
at the site of inflammation leading to the formation of strong oxi-
dant and nitrating species (
Ascenzi, Bocedi, et al., 2006; Goldstein, Lind, &
Mer´nyi, 2005
). Peroxynitrite detoxification by
M. leprae
2/2HbO has been
shown to be rapid; therefore, 2/2HbOmight be an important contributor to
such function (
Ascenzi, Milani, &Visca, 2006
). Furthermore, as reported for
NO and NO
2
(
Ascenzi et al., 2008
), peroxynitrite acts as an antioxidant
preventing the
M. leprae
2/2HbO
d
Fe(IV)
]
O-mediated oxidation of
mycobacterial (macro)molecules such as membrane lipids (i.e. lipid perox-
idation) (
Ascenzi et al., 2009
).
The defence mechanisms against reactive oxygen and nitrogen species
represent important components in the evolutionary adaptations, particu-
larly under extreme environmental conditions. In this framework,
in vivo
and
in vitro
experiments have been performed in order to understand the
roles of group II 2/2HbO from the Antarctic bacterium
Pseudoalteromonas
haloplanktis
TAC125 (encoded by the
PSHAa0030
gene) in NO detoxifica-
tion mechanisms (
Coppola et al., 2013
). The presence of multiple genes
encoding 2/2Hbs and a flavohaemoglobin in this bacterium strongly
