A History of Iron Metabolism in the Mycobacteria - Iron Acquisition by the Genus Mycobacterium - page 22

ATCC 19698) by Richard Merkal, could only find mycobactin J as a minor com-
ponent at <10 % of the total mycobactins that they extracted from the same strain
as used by Merkal himself. The major mycobactin of this species, in our hands,
was equivalent to the mycobactin from M. intracellulare M12, which is part of
the avium complex of mycobacteria. It now appears that the original culture of M.
paratuberculosis strain 18 probably had been taxonomically misnamed [ 69 , 70 ]
and should therefore be regarded as a strain of M. avium .
What the reasons were for mycobactin J being the dominant siderophore when
NADC 18 strain was grown in Merkal's laboratory but not in the UK remains
unsolved but clearly there must be some subtle regulatory mechanism that can
cause such a shift. Mycobactin J remains the only commercially available myco-
bactin and, because of its structural similarities to the main mycobactins, is able to
stimulate the growth of both a number of isolates and mutants that are being gen-
erated with defects in their iron metabolic pathways.
Hall and Ratledge [ 71 ] also isolated mycobactin-like materials from three out of
11 species of Rhodococcus : R. bronchialis, R. terreus and R. rubropertinctus and
suggested that the latter two species might be equivalent to each other. Although
no structural determinations were carried out, the similarity of these new materi-
als to the mycobactins was apparent and they should have been, but were not,
named as rhodobactins. Some species of Rhodococcus , including R. rhodochrous ,
did not, however, produce a 'rhodobactin'. Some 20 years later, Dhungana et al.
[ 72 ] isolated a siderophore from R. rhodochrous , albeit from a different strain to
that of Hall and Ratledge, with hexadecane as the sole carbon source. This sidero-
phore was named rhodobactin but it was present in the culture medium and was
not apparently in the cells. It was therefore distinct in structure to the mycobactins
having two catecholate and one hydroxamate moieties for iron chelation instead of
having a salicyloyl and two hydroxamate moieties and without a long alkyl chain
for lipid solubility. Pedantically, the name 'rhodobactin' is therefore incorrect as it
would imply similarity to the mycobactins and nocobactins.
2.4.3 Salicylic Acid
The story of the mycobactins and iron metabolism was then taken up by the author
of this review. I carried out research work, as post-doctoral fellow, with Frank
Winder in Dublin from October 1960 to June 1964 being asked to focus on the
metabolic consequences of iron-deficiency in M. smegmatis being used as a model
organism for the tubercle bacillus. The first significant finding [ 73 ] was the identifi-
cation of salicylic acid that accumulated up to about 17 μ g/ml in the medium of iron
deficiently grown cells whereas in iron replete medium only about 0.6 μ g salicylic
acid/ml was found (see Fig. 2.6 ). However, a mistake was made in the latter part of
this paper when the concentrations of salicylic acid were being given for M. tuber-
culosis and M. phlei . The 'salicylic acid' in the latter species had only been verified
by simple paper chromatography where it ran with the same Rf value as authentic