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The Iron Response of Mycobacterium tuberculosis and Its Implications for Tuberculosis Pathogenesis and Novel Therapeutics - PubMed

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The Iron Response of Mycobacterium tuberculosis and Its Implications for Tuberculosis Pathogenesis and Novel Therapeutics

G Marcela Rodriguez et al. Front Cell Infect Microbiol. 2022.

Abstract

Most pathogenic bacteria require iron for growth. However, this metal is not freely available in the mammalian host. Due to its poor solubility and propensity to catalyze the generation of reactive oxygen species, host iron is kept in solution bound to specialized iron binding proteins. Access to iron is an important factor in the outcome of bacterial infections; iron limitation frequently induces virulence and drives pathogenic interactions with host cells. Here, we review the response of Mycobacterium tuberculosis to changes in iron availability, the relevance of this response to TB pathogenesis, and its potential for the design of new therapeutic interventions.

Keywords: IdeR; M. tuberculosis; extracellular vesicles; ferritin; iron-limitation; iron-response.

Copyright © 2022 Rodriguez, Sharma, Biswas and Sharma.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1

Summary diagram of the Mtb response to iron availability. Iron limited Mtb upregulates expression of genes encoding siderophore synthesis (mbt), export (MmpL4/5-MmpS4/5), and import (IrtAB). Assimilated iron is incorporated into metalloproteins and stored in ferritins. Iron deficient Mtb also upregulates pathogenicity factors that facilitate immune evasion and proliferation, modifies its cell surface, and augments EVs secretion. Prolonged iron deprivation induces a strong iron sparing response and metabolic rewiring that enables long term persistence without replication and leads to phenotypic antibiotic resistance. These changes are fully reversible by restoring iron availability. Iron sufficient Mtb engages IdeR to control intracellular iron levels via repression of iron uptake and stimulation of iron storage, thus preventing iron dysregulation and oxidative stress that renders this pathogen highly vulnerable to host antimicrobial factors and antibiotic drugs. The figure was created with BioRender (

BioRender.com

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