A History of Iron Metabolism in the Mycobacteria - Iron Acquisition by the Genus Mycobacterium - page 4

2.1 Introduction
In writing this review I have attempted to cover as much as possible of the early
research work of how our understanding of iron metabolism has developed over
the past six or seven decades as this material now receives little, if any, mention in
current research papers or reviews. However, there are many nuggets of valuable
information tucked away in many of these early papers that should not be forgot-
ten as they can help to identify aspects of the topic that still need investigation and
explanation.
Iron metabolism does not, though, have a long history. The real beginnings only
start in the 1950s through the work of Frank Winder. He was the pioneer in this
area as he was the first to appreciate that, in order to study how iron was metabo-
lized, it was necessary to know how much iron was needed by the mycobacteria to
grow. It was then essential to prepare culture medium with as much iron as pos-
sible being removed from it; this then provided the first culture media that were
genuinely, and knowingly, iron deficient. Thus, Winder's research group in Dublin,
Ireland, was then the first group to be engaged on understanding the consequences
of iron deprivation in mycobacteria. This deprivation of iron in the growth medium
was the essential first step in understanding how iron was assimilated into the bac-
teria. Now, many laboratories throughout the world are actively pursuing a variety
of aspects of the subject but these still have a long way to go before the problems
of iron metabolism, both in vitro and in vivo, could be considered as being solved.
The importance of iron in the growth and multiplication of the tubercle bacil-
lus, and other pathogenic mycobacteria has gradually been appreciated over the
past three or four decades as it has been increasingly realized that iron-deficient
growth conditions are the 'natural' state for pathogenic bacteria to be in when they
are causing infections in a host animal. Thus, from the early work of Frank Winder
from the 1950s and into the 1970s has developed a crucial understanding of how
mycobacteria are able to acquire the iron that is essential for their growth and mul-
tiplication when causing tuberculosis and related mycobacterial diseases.
The other pioneer in this field was Alan Snow who was involved in the dis-
covery of the mycobactins that were subsequently to become central to the iron
metabolism story. However, the involvement of the mycobactins with iron only
came in the 1960s, some 20 years after the initial descriptions of the molecule.
By this time, interest in mycobactins, as possible target molecules for the design
of rational anti-tuberculosis agents, had faded and with only one or two groups
then pursing the biochemical puzzles that had been opened up by the discovery of
these unique microbial siderophores. Interestingly, however, these early thoughts
of synthesizing novel mycobactin antagonists are now being re-visited as the need
for novel chemotherapeutic agents for the treatment of tuberculosis becomes ever-
more urgent.
I hope, therefore, that this early history of the subject will be of interest to read-
ers. I have placed much less emphasis on developments over the past 10-15 years
as, although a lot is now happening in many laboratories, these aspects are mainly
focusing on filling in the details of individual parts of the overall picture and are,