Biology Reference
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also grew faster and reached a higher final OD than control cells (
Pathania,
Navani, Rajamohan, et al., 2002
), suggesting a contribution to growth of
the cells, perhaps bymore efficient aerobic respiration. As previously discussed,
trHbO is expressed throughout growth in
M. bovis
as detected by Western
Blotting (
Mukai et al., 2002; Pathania, Navani, Rajamohan, et al., 2002
),
which adds credence to the assumption that trHbO can aid respiration.
Liu
et al. (2004)
additionally comment that trHbO may act as an O
2
collector
or reservoir to support respiration in hypoxic conditions.
However, if trHbO is to be implicated in aerobic metabolism, we must
be able to link this function back to the biochemistry of the protein. The
combination rate for Mtb trHbO and O
2
is
<
1.0
M
1
s
1
and the disso-
ciation rate is
<
0.006 s
1
; coupled with the very high affinity for O
2
(
Ouellet et al., 2003
), these data suggest that once trHbO has trapped O
2
in the haem pocket, it will stay there which is contrary to a role in O
2
capture
and delivery. These authors suggest that trHbO may play a role in sensing
the redox state of the cell. However, as
Liu et al. (2004)
found, trHbO dis-
sociates from a dimer into a monomer during its interaction with membrane
lipids, and this change may alter the affinity of the globin for O
2
. A definitive
answer remains to be found.
As has already been discussed, flavoHbs are traditionally thought of as
NO detoxification proteins, as shown in
E. coli
(
Stevanin et al., 2000
)
and
S. typhimurium
(
Stevanin et al., 2002
). However, the recently discovered
flavoHb of
M. tuberculosis
appears to have a different function. When
expressed in
E. coli
, cells expressing MtbFHb showed NO consumption
of 5.32 nmol NO haem
1
s
1
, in comparison with wild-type values of
1.14 nmol NO haem
1
s
1
, a difference that was not deemed significant
(
Gupta et al., 2011
). The same cells showed slightly improved O
2
uptake
(7.1
m
mol min
1
10
9
cells
1
in wild type). These data suggest that MtbFHb has a different function alto-
gether. A second paper from the same group implicated MtbFHb in the oxi-
dation of
D
-lactate into pyruvate; this was first proposed due to the
similarities between the FAD-binding domain of MtbFHb and
D
-lactate
dehydrogenase (
Gupta et al., 2012
). Indeed, during oxidative stress, as deliv-
ered by sub-lethal concentrations of hydrogen peroxide,
E. coli
and
M. smegmatis
cells carrying MtbFHb showed improved survival; further
investigations showed that there were reduced levels of lipid peroxidation
and the authors suggested that MtbFHb is protecting the cell membrane
from lipid peroxidation during oxidative stress. Additionally, the promoter
of the MtbFHb gene showed increased activity in the presence of hydrogen
mol min
1
10
9
cells
1
compared with 5.3
m
m
