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Chapter 5
Siderophore-Mediated Iron Acquisition:
Target for the Development of Selective
Antibiotics Towards Mycobacterium
tuberculosis
Raúl E. Juárez-Hernández, Helen Zhu and Marvin J. Miller
Abstract This chapter reviews recent pertinent literature on the Mycobacterium
tuberculosis siderophore mycobactin and its excreted counterpart carboxymy-
cobactin. Emphasis is placed on the design of antibiotics to specifically interfere
with the biosynthesis of these siderophores and the use of siderophore analogs
or conjugates to achieve inhibition of M . tuberculosis . Although the discussion is
focused on biological activity of potential anti-tuberculosis agents, a brief descrip-
tion of the synthetic routes for compounds of interest is given.
Keywords Mycobacterium tuberculosis  • TB • Mycobactins • Siderophore •  
Siderophore-antibiotic conjugates • Antibiotics • Sideromycins • MDR (multi-drug 
resistant) • XDR (extensively-drug resistant) • Biosynthesis inhibitors
5.1 Introduction
Approximately one out of every three people living on this planet is infected with
M . tuberculosis, the causative agent of the contagious disease tuberculosis (TB). It
is estimated that in 2009, close to 1.7 million of people died because of this infec-
tion [ 1 ]. Similar to the emergence of other antibiotic-resistant bacteria, the diagno-
sis of multi-drug resistant (MDR) and extensively-drug resistant (XDR) strains of
M. tuberculosis [ 2 ] has sparked interest around the world to develop new agents
that can be used to eradicate disease caused by this deadly microorganism [ 3 - 11 ].
R. E. Juárez-Hernández ( * ) · H. Zhu · M. J. Miller
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN,
USA
e-mail: rxj159@case.edu
M. J. Miller
e-mail: mmiller1@nd.edu
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