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IdeR is required for iron homeostasis and virulence in M ycobacterium tuberculosis
Author(s) -
Pandey Ruchi,
Rodriguez G. Marcela
Publication year - 2014
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12441
Subject(s) - biology , virulence , mycobacterium tuberculosis , tuberculosis , regulator , iron homeostasis , function (biology) , microbiology and biotechnology , virulence factor , bacteria , mutant , siderophore , intracellular , genetics , gene , medicine , pathology
Summary Iron is an essential but potentially harmful nutrient, poorly soluble in aerobic conditions, and not freely available in the human host. To acquire iron, bacteria have evolved high affinity iron acquisition systems that are expressed under iron limitation often in conjunction with virulence determinants. Because excess iron can be dangerous, intracellular iron must be tightly controlled. In mycobacteria, IdeR functions as a global iron dependent transcriptional regulator, but because inactivation of ideR is lethal for M ycobacterium tuberculosis , it has not been possible to use genetics to fully characterize this protein's function or examine the requirement of iron regulation during tuberculosis infection. In this work, a conditional M . tuberculosis ideR mutant was generated and used to study the basis of IdeR 's essentiality. This investigation uncovered positive regulation of iron storage as a critical aspect of IdeR 's function in regular culture and a prominent factor for survival under stresses associated with life in macrophages. Moreover, this study demonstrates that IdeR is indispensable in the mouse model of tuberculosis, thereby linking iron homeostasis to virulence in M . tuberculosis.