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have been reported not only in eukaryotes and multicellular organisms but in
many bacteria too. Since there is little evidence that the
Vitreoscilla
globin is
important in NO biochemistry, the tacit assumption is that VHb functions
in these numerous examples as an oxygen transport protein (
Khosla &
Bailey, 1989
). This conclusion should be borne in mind when considering
the roles of globins of all classes in eukaryotic microbes.
Nevertheless, within unicellular organisms, there are plausible alterna-
tives to oxygen storage and transport for the functions of globins. One is
the protective role of globins, demonstrated most convincingly for FHbs,
against nitrosative stress (
Angelo, Hausladen, Singel, & Stamler, 2008;
Forrester & Foster, 2012a; Gardner, 2005, 2012
). The other, suggested
by E. van Holde (Oregon State University), is the sensing of changes in oxy-
gen concentration, leading to a role in regulating chemotaxis, providing the
means for the host microorganism to migrate towards optimal oxygen con-
centrations (
Vinogradov, Hoogewijs, Vanfleteren, et al., 2011
).
Numerous studies over the last decade have demonstrated that FHbs play a
role in the response of pathogenic microorganisms to the nitric oxide gener-
ated by the innate immune system (
Angelo et al., 2008; Brown, Haynes, &
Quinn, 2009; Forrester & Foster, 2012a
). The FHbs protect against the toxic
effects of nitric oxide via their catalysis of the conversion of NO and oxygen to
nitrate anion. The overall reaction discovered by Gardner and his collabora-
tors (
Gardner, 2005, 2012; Gardner, Gardner, Martin, & Salzman, 1998
)has
been the subject of heated debate regarding the mechanism, with advocates
for both the dioxygenase route first proposed by Gardner and the denitrosylase
mechanism, championed by Stamler and colleagues (see
Forrester & Foster,
2012a, 2012b; Hausladen & Stamler, 2012
). Whatever the mechanism,
the robust abilities of FHbs to remove and detoxify NO is one of the most
important defences against reactive nitrogen intermediates in the repertoire
of microbial pathogens. Without this protein, the virulence of many patho-
gens is attenuated, and FHbs have been demonstrated to be important for
survival in human macrophages (e.g. in
Salmonella
,
Gilberthorpe, Lee,
Stevanin, Read, & Poole, 2007; Laver et al., 2010; Stevanin, Poole,
Demoncheaux, & Read, 2002
). There are extensive reviews of this topic
(
Bowman, McLean, Poole, & Fukuto, 2011; Laver et al., 2013
).
6.2. Yeasts
Before the advent of molecular cloning or sequencing approaches, studies of
microbial globins were fragmentary. Nevertheless, two landmark studies
