A History of Iron Metabolism in the Mycobacteria - Iron Acquisition by the Genus Mycobacterium - page 11

Such is the need to scavenge whatever iron might be available from the envi-
ronment, so as to rescue the cells from their 'anaemia', that it is therefore not sur-
prising to observe that much metabolic effort is expended by the iron-deficient
mycobacterium to acquire iron from its environment. Iron deficiency, however,
is not just a man-made artificial construct for laboratory cultivation experiments.
There is good reason now to consider that iron deficiency is the normal sta-
tus of pathogenic mycobacterium within the animal tissue which it is infecting.
Pathogenic mycobacteria therefore must overcome the natural defenses of the
infected host animal that seeks to withhold iron from the invading bacteria. Unless
a pathogen, and not just a mycobacterium, can acquire iron from its host, it will
not be able to grow and thus become pathogenic. Gaining iron is therefore pos-
sibly the first step for an invading bacterium to achieve in order to grow in vivo.
Thus, the mechanisms of iron acquisition by mycobacteria are of prime concern if
we are to understand anything about the pathogenicity of these bacilli.
2.4 Early Discoveries of the Major Components of Iron
Acquisition by Mycobacteria
2.4.1 The Mycobactins
The first clues about how iron might assimilated by mycobacteria came very indi-
rectly from the initial observations by Twort and Ingram [ 22 - 24 ] when they were
attempting to cultivate the mycobacterium that was the causative agent of Johne's
disease in cattle. However, it would be more than 50 years before it would be
appreciated how these early observations, and the subsequent discoveries arising
from them, fitted in with iron metabolism to unravel a major and unique feature of
mycobacterial metabolism.
Johne's disease in cattle causes chronic enteritis and was found to be caused by
a mycobacterium that was then called M. johnei [ 25 ] but was re-named as M. para-
tuberculosis . This name is therefore used in the remainder of this review although
more recent taxonomic work has re-classified the bacillus yet again, as mentioned
below. The organism, very importantly for the iron assimilation story, could not be
cultivated in ordinary laboratory medium but Twort and Ingram [ 22 - 24 ] found that
by supplementing the egg-based medium they were using with dry, killed human
tubercle bacilli they could then achieve good growth of this previously uncultivat-
able Mycobacterium species. Animal tissues and extracts were ineffective. They
subsequently found that other killed mycobacteria could also support growth:
these included M. phlei , M. smegmatis , and M. butryicum as well as other less-
well defined mycobacteria. Also extracts from the killed mycobacteria prepared
using organic solvents were equally successful in promoting growth. The conclu-
sion was reached that M. paratuberculosis lacked the ability to synthesize some
essential growth factor but that this material was synthesized by several competent