Mycobacterial Iron Acquisition Mechanisms - Iron Acquisition by the Genus Mycobacterium - page 43

Table 3.1 The Iron Fulcrum in Infectious Diseases a
Pathogen
Iron acquisition factors

Host
Iron-withholding defenses

Iron

Ferric siderophores (bind iron from
host iron containing molecules
including transferrin, lactoferrin,
ferritin, except heme)

Iron management system;
Hypoferremic response;
Siderocalin inactivation
of siderophores

Ferrous uptake (surface or excreted
reductases)
Transferrin receptors (possible
reduction with subsequent
ferrous uptake)
Heme receptors and uptake
(digestion of heme-proteins)

Heme and hemoglobin binding
proteins (hemopexin, haptoglobin)

Other? Other?

a Modiied from Ref. [ 14 ]

the iron fulcrum in its favor to gather iron, survive and multiply. The dangerous
but necessary reactivity of iron in metabolism means that inadvertent exposure of
iron must be avoided. This is accomplished with an iron management process that
moves iron throughout the vertebrate host while bound in ferric-transferrin and
which also produces protective iron storage molecules that sequester the metal.
This iron control process creates an iron-poor circumstance that tends to seclude
the metal from the microbial invader. When faced with a microbial infection the
host may mount the so-called hypoferremic response in which the iron concentra-
tion in transferrin is drastically lessened. Some pathogens use their siderophores to
capture iron from the host but recently the host protein siderocalin was shown to
be another player in the iron-withholding defense strategies. Siderocalin inactivates
some siderophores, forcing productive pathogens to synthesize siderophores resist-
ant to siderocalin. However, successful pathogens have overcome the iron-with-
holding restrictive barriers. Reviews on the subject of iron and infection [ 15 - 21 ]
and Chapter Four of the present volume should be consulted for more information.

3.3 The Mycobacterial Siderophores and Iron Acquisition:
Mycobactin, Carboxymycobactin, and Exochelin

An exhaustive review of the literature on iron acquisition in the mycobacteria
will not be made; recent pertinent reviews should be consulted for detailed earlier
information [ 18 , 22 - 24 ], (also see Chap. 2 ) . Evidence from gene expression stud-
ies shows that M. tuberculosis faces iron restriction during growth in lungs and
human macrophages and mutant strains deficient in iron acquisition are attenuated
for growth in macrophages [ 22 , 23 , 25 - 28 ].