A History of Iron Metabolism in the Mycobacteria - Iron Acquisition by the Genus Mycobacterium - page 18

author of this chapter has been privileged to receive the original letters concern-
ing the mycobactins that had been sent and received by Philip Hart. Hart pub-
lished one paper dealing with the growth of M. johnei in a mycobactin-containing
medium [ 46 ]. Philip died in 2006 aged 106 having remained active in research
until his final 2 years.
The question of how M. paratuberculosis was able to grow in vivo and acquire
iron from the host was not solved until much later although Norman Morrison,
working at the Johns Hopkins University, found that M. paratuberculosis could,
in fact, grow without mycobactin if the pH of the growth medium was dropped
to 5.5, or even to 5.0 as was later reported by Lambrecht and Collins [ 47 ]. This,
it was suggested, might then mimic the conditions of growth in vivo and might
be enough to increase the solubility of free iron to the point where it could now
be acquired without the need for mycobactin. A (partial) resolution of this prob-
lem came, however, by the demonstration by Barclay and Ratledge [ 48 ] that
M. paratuberculosis and other mycobactin-dependent strains of Mycobacterium
could synthesize the extracellular counterpart to mycobactin, that is carboxymy-
cobactin, and this would then be the way in which iron was acquired by the cells.
2.4.2 Other Mycobactins and Related Lipid-Soluble
Siderophores
Once Alan Snow had solved the structure of mycobactin and worked out the main
ways in which it could be extracted and characterized, the way was open for other
workers to build on this work and examine other mycobacteria and genera related
to the Mycobacterium genus for the presence of other iron binding compounds.
The presence of materials similar to mycobactin was noted by Patel and
Ratledge [ 49 ] in species of Nocardia. The genus of Nocardia is taxonomically
closed related to the mycobacteria and both are members of the actinomyces
group of bacteria and have similar cell walls with a high content of lipid. It is
therefore not too surprising that similar iron-binding compounds would then be
found in these species. These were then named nocobactins and the structure of
that from N. asteroides , termed nocobactin NA, was then elucidated by Ratledge
and Snow [ 50 ]. This is shown in Fig. 2.5 where it is labeled as type a . It resembled
the structure of mycobactin M (Fig. 2.4 ) but had a distinctive oxazole ring instead
of an oxazoline ring and with a shorter alkyl chain. This type of nocobactin was
also detected in N. paraffinae, N. sylvodorifera and N uniformis [ 51 ]. Two other
types of nocobactin were found: type b (which is then known as nocobactin NB)
was from N. brasiliensis , and type c , or nocobactin NC, was from N. caviae and
N. phenotolerans . The latter types were similar to mycobactins S and T but had
saturated alkyl chains rather than the unsaturated chains of the latter materials.
Once it was appreciated that iron deficient growth of a mycobacterium would
increase the content of mycobactin by up to a 100-fold, it was then a relative
easy matter to develop simpler methods of producing it. In our own work with