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the majority of Type II flavoHbs of pathogenic bacteria. The flavoHb in the
non-pathogenic species has an aldose epimerase gene down-stream and a
gene encoding a hypothetical protein (proposed to be an integral membrane
protein) upstream of it. Thus, a clear-cut distinction is present in the geno-
mic organisation of flavoHb-encoding genes of pathogenic and non-
pathogenic Mycobacteria.
Genetic regulation studies on the MtbFHb-encoding gene (Rv0385)
indicated that its promoter activity increases gradually up to 24 h post-
infection, showing a three-fold increase in promoter activity, which was
reduced to basal level after 48 h (Pawaria, Lama and Dikshit, unpublished).
This suggests a stage-specific and high level up-regulation of Rv0385 during
intracellular infection of M. tuberculosis .
5. BIOLOGICAL FUNCTIONS OF trHbs AND FlavoHbs
This is not the place for a detailed review of the host response to infec-
tion by Mycobacteria; for more details, see Liu and Modlin (2008) . How-
ever, in order to understand the biological functions of trHbN and trHbO,
we must have an appreciation of the pathogenicity of, in particular,
M. tuberculosis . A 1999 report for WHO documented that in 1997, there
were just under 8 million new cases of TB worldwide, in addition to
16.2 million existing cases of TB; 1.87 million people died of TB in the same
year ( Dye, Scheele, Dolin, Pathania, &Raviglione, 1999 ), emphasising how
important it is to study mechanisms of disease. Upon infection of the host ,
M. tuberculosis can either cause TB or enter into a dormancy mode inside
macrophage phagosomes, where they will encounter hypoxic conditions
and probably NO from the NOS enzymes. It is thought that trHbN and
trHbO are important proteins for M. tuberculosis when inside the macro-
phage; their biological functions will be discussed here.
5.1. Nitric oxide scavenging
Studies into the biological functions of trHbN have been done in
M. tuberculosis , M. bovis and M. smegmatis . The first evidence for function
came in M. bovis . The glbN gene was inactivated via gene insertion of a kana-
mycin cassette; no difference in growth in liquid or in solid media was
observed compared with wild-type cells, suggesting that Mb trHbN is
not essential for growth under normal laboratory conditions ( Ouellet
et al., 2002 ). As other globins, notably flavoHb from E. coli , are implicated
in NO detoxification ( Stevanin et al., 2000 ), NO metabolism was
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