Introduction to the Topic - Iron Acquisition by the Genus Mycobacterium - page 2

human iron management process secludes iron from an invading pathogen, creat-
ing an iron-poor situation for the pathogen. Some pathogens use their siderophores
to interrupt their host's iron circuit.
1.2 Scope of the Book
Our subject is the mechanism of iron acquisition by the genus Mycobacterium ,
a ubiquitous group that is composed of both saprophytic and pathogenic types,
including the devastating pathogen M. tuberculosis . Almost all mycobacteria pro-
duce both a cell associated water-insoluble siderophore mycobactin and a modi-
fied mycobactin termed carboxymycobactin that is water soluble and excreted
from the cells. The saprophytic mycobacteria elaborate and excrete yet another
siderophore exochelin not found in the pathogenic types.
Siderophore discovery and isolation in the mycobacteria have an interesting
history and Colin Ratledge, the authority on this subject, first will trace the histori-
cal aspects of siderophores in the mycobacteria from a unique personal viewpoint.
His handiwork and that of other pioneer scientists interested in mycobacterial
iron uptake launched the current studies, forming the platform on which these are
based. It is unlikely that a unique work similar to Chap. 2 on the history of myco-
bacterial iron acquisition is, or will become, available.
Mycobacterial iron uptake is complex and excellent recent reviews on M.
tuberculosis iron acquisition systems are available. In Chap. 3 , I will attempt to
summarize recent research on iron uptake in both pathogenic and saprophytic
mycobacteria with special interest on the genetics of these processes.
Not only does the human iron handling system tend to withhold iron from
microbial pathogens, other iron related host defenses are quickly mounted. Host
production of siderocalin has been added as another player because siderocalin
can bind and inactivate some siderophores, requiring a pathogen to either modify
its siderophore or produce another siderophore that resists siderocalin inactivation.
In Chap. 4 , Benjamin Allred, Allyson Sia and Kenneth Raymond will detail the
potential role of siderocalin in a mycobacterial infection.
The rise of multiple drug resistant strains of M. tuberculosis brings us to the
crucial question for humanity: because iron is critical for mycobacterial growth,
can what we know of the mycobacterial iron acquisition mechanisms be used to
develop effective treatments for tuberculosis? Approaches to this question include
synthesis of siderophore analogs and conjugation of siderophores with toxic
agents. In Chap. 5 , Raul Jaurez-Hernandez, Helen Zhu and Marvin Miller will
describe the important recent developments in the use of the mycobacterial iron
uptake processes in the potential development of anti-tuberculosis drugs.