A History of Iron Metabolism in the Mycobacteria - Iron Acquisition by the Genus Mycobacterium - page 17

Following the descriptions of the structures of the first two mycobactins, P and
T, [ 35 , 36 ] the structures of other mycobactins were elucidated during the remain-
ing years of the 1960s by Snow who had now been joined by a very able technical
assistant, Mr. A. J. White. Mycobactins S and H types from, respectively, M. smeg-
matis and M. thermoresistible [ 43 ] were described; this was followed by descrip-
tions of the mycobactins from M. aurum , M. terrae , M. fortuitum and M. marinum
that were labeled as types A, R, F and M and N, respectively [ 44 ]. The structures
of all the mycobactins that were determined by Alan Snow are given in Fig. 2.4 .
It is probably worth repeating the observations made in this final paper that the
mycobactins M and N, both from M. marinum , were inhibitory towards M. tuber-
culosis and these two mycobactins were distinctively different from the mycobac-
tins from other mycobacteria in having the characteristic long alkyl chain attached
to a different part of the molecule (Fig. 2.4 ). This observation, however, does not
appear to have been taken up by any other group looking to realize the potential
of designing inhibitors of M. tuberculosis when this work of Snow and colleagues
began 25 years earlier. These papers were, in fact, the last significant publications
arising from the work at ICI Ltd. Alan Snow, himself, wrote a review of the myco-
bactins which remains the definitive account of the chemistry and major properties
of these iron-binding compounds [ 26 ]. It is still quoted in many research papers
today. This review contains many details that are still salient today; this includes
considerable information on the binding of metal ions to the molecule including,
of course, iron. The tenacity of mycobactin for iron is the major feature of the
molecule and Snow, on the basis of desferrimycobactin being able to remove the
iron from ferric-desferrioxamine B [ 45 ], calculated that its stability constant was
well in excess of 10 30 . The mycobactin project at ICI Ltd came to a close at the
end of the 1960s with Snow himself then retiring about a decade later. The orig-
inal objectives of the research, however, had not been fulfilled though consider-
able interest is still evident to-day in looking at aspects of iron metabolism in the
mycobacteria for opportunities to design novel anti-tuberculosis agents. This topic
is then re-visited by other contributors in this monograph.
Alan Snow appears to have received many requests for samples of mycobac-
tin P once it was firmly established that this was the growth factor essential for
the growth of johne's bacillus. I have already commented on some correspond-
ence between Alan and Philip D'Arcy Hart at the MRC Laboratories in London.
Hart was not only wanting to grow M. johnei, as it was still referred to then,
but also the leprosy bacillus, M. leprae , and the rat leprosy bacillus, M. leprae-
murium . Also pursuing the same objectives was John Hanks at Johns Hopkins
University, Baltimore, who also had received samples of mycobactin from Snow.
Unfortunately, in spite of many attempts both in London and Baltimore, the lep-
rosy bacillus in neither location showed any sign of growth in mycobactin-supple-
mented medium.
The correspondence between Hart and Snow began in 1955 and continued up
to 1972 with Snow finally concluding (October 26th, 1972) that “(o)ur own stocks
of mycobactin P are quite low now, because we have given so much away but we
can still help (you) with small quantities when required (in a good cause!)”. The