Biology Reference
In-Depth Information
Chapter 4
Siderocalin Combats Mycobacterial
Infections
Benjamin E. Allred, Allyson K. Sia and Kenneth N. Raymond
Abstract
The human immunoprotein siderocalin (Scn) protects against infections
by binding the siderophores used by a pathogen to steal iron from host iron stores,
thereby limiting bacterial growth and subsequent colonization by restricting the
supply of iron.
Mycobacterium tuberculosis
synthesizes two siderophores, myco-
bactin and carboxymycobactin, with the same core structure. Unlike the alkyl side
chain of mycobactin, the carboxylate chain of carboxymycobactin imparts water
solubility on this siderophore, allowing it to be excreted. The variable length of
the carboxymycobactin chain markedly influences binding by Scn. The structural
differences in the side chains of mycobactin and carboxymycobactin and the intra-
cellular location of
M. tuberculosis
challenge the ability of Scn to recognize and
inactivate siderophore-mediated iron acquisition by this pathogen. We describe the
physical interactions between Scn and carboxymycobactin as well as the effect of
Scn on the growth of
M. tuberculosis
in different cellular environments. The evi-
dence suggests that Scn is part of the defenses that prevent or limit infections of
M. tuberculosis
.
Keywords
Siderocalin • Carboxymycobactin • Mycobactin • Carboxymyc
obactin variable side chain length • Carboxymycobactin-siderocalin binding •
Siderocalin immune defense against mycobacterial infections
B. E. Allred · A. K. Sia · K. N. Raymond (
*
)
University of California, Berkeley, CA, USA
e-mail: raymond@socrates.berkeley.edu
B. E. Allred
e-mail: ballred7@berkeley.edu
A. K. Sia
e-mail: allysonksia@berkeley.edu
Search WWH ::
Custom Search