A History of Iron Metabolism in the Mycobacteria - Iron Acquisition by the Genus Mycobacterium - page 6

principal form of iron storage in animal cells. A similar form of it, bacterioferritin,
exists in bacteria, including mycobacteria, for the same function.
In haemoglobin and other haem containing molecules iron is tightly bound as
the ferrous ion and therefore, for metal release, the molecule must be degraded.
This occurs principally with haemolytic bacteria which therefore excludes most
pathogenic mycobacteria.
To achieve release of iron from transferrin and ferritin requires that pathogenic
bacteria, including mycobacteria, must either attack the protein itself by secret-
ing various proteases, use a ferric reductase that would generate ferrous ions that
might then be directly assimilated, or, alternatively, use molecules of very high
iron binding strength that can then, literally, strip the iron out of the molecules.
The materials that can do this are known as siderophores and those relevant to the
mycobacteria will be covered in this review and also elsewhere in this monograph.
Thus, we can conclude that all mycobacteria, whether pathogenic or sapro-
phytic, require iron and that the acquisition of iron from whatever source requires
specific mechanisms for achieving this.
2.3 Iron as an Essential Nutrient for Mycobacteria
In the early days of mycobacteriology, iron was 'guessed' to be an essential minor
trace element and workers, such as Sauton [ 3 ], in devising appropriate growth
medium for the cultivation of mycobacteria, recommended that iron be added to
the culture medium at 10 μ g/ml. Obviously, this was an empirical amount but
later workers [ 4 - 6 ] were able to confirm that iron was indeed required to achieve
full growth of various mycobacteria. Edson and Hunter [ 4 ] indicated that, for
M. phlei , 3.75 μ g Fe/ml was needed for full growth but Turian [ 6 ] revised this to
just 1 μ g/ml. Clearly, the amount of iron added to the medium would depend on
the amounts of iron which were adventitiously included by other ingredients of the
medium. Nor should the presence of iron in the water or in the glassware being
used for cultivation be ignored. Thus, to establish what amounts of iron might be
necessary for growth it was first necessary to prepare culture medium that with as
little iron as possible. This was first appreciated by Frank Winder who then pio-
neered a series of in-depth studies on the role of iron in the metabolism of the
mycobacteria.
Frank Winder (Fig. 2.1 ) carried out all his work on the mycobacteria at Trinity
College, Dublin, Republic of Ireland, starting from about 1953 and continuing
to his death in 2007 at the age of 79. Initially, Winder's work was done in the
Laboratories of the Medical Research Council of Ireland and then later in the
Department of Biochemistry also within the College. In a seminal paper in which
the conditions of iron deficient (and also zinc deficient) growth of a mycobacte-
rium ( Mycobacterium smegmatis ) were first described, Winder and Denneny [ 7 ]
observed that when some, but not all, cultures of the bacterium were grown in
modified Proskauer and Beck medium to which no iron or other trace elements