Iron Deprivation Affects Drug Susceptibilities of Mycobacteria Targeting Membrane Integrity

Journal of Pathogens
Rahul PalZeeshan Fatima

Abstract

Multidrug resistance (MDR) acquired by Mycobacterium tuberculosis (MTB) through continuous deployment of antitubercular drugs warrants immediate search for novel targets and mechanisms. The ability of MTB to sense and become accustomed to changes in the host is essential for survival and confers the basis of infection. A crucial condition that MTB must surmount is iron limitation, during the establishment of infection, since iron is required by both bacteria and humans. This study focuses on how iron deprivation affects drug susceptibilities of known anti-TB drugs in Mycobacterium smegmatis, a "surrogate of MTB." We showed that iron deprivation leads to enhanced potency of most commonly used first line anti-TB drugs that could be reverted upon iron supplementation. We explored that membrane homeostasis is disrupted upon iron deprivation as revealed by enhanced membrane permeability and hypersensitivity to membrane perturbing agent leading to increased passive diffusion of drug and TEM images showing detectable differences in cell envelope thickness. Furthermore, iron seems to be indispensable to sustain genotoxic stress suggesting its possible role in DNA repair machinery. Taken together, we for the first time established a lin...Continue Reading

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Citations

Oct 19, 2016·The Brazilian Journal of Infectious Diseases : an Official Publication of the Brazilian Society of Infectious Diseases·Rahul PalZeeshan Fatima
Jul 25, 2017·Journal of Global Antimicrobial Resistance·Sandeep HansZeeshan Fatima
Jul 27, 2018·The Journal of Eukaryotic Microbiology·Wendy Argáez-CorreaJulio C Torres-Romero
Sep 19, 2018·Drug Discoveries & Therapeutics·Siddhartha KumarAntresh Kumar
Jun 8, 2018·Current Drug Discovery Technologies·Shrayanee DasZeeshan Fatima
Jun 21, 2018·Frontiers in Cellular and Infection Microbiology·Ruan FourieCarolina H Pohl
Nov 16, 2018·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Rahul PalZeeshan Fatima

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Methods Mentioned

BETA
dissect
environmental stress

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