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Vitamin C: A Natural Inhibitor of Cell Wall Functions and Stress Response in Mycobacteria

  • Kirtimaan Syal
  • Dipankar ChatterjiEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1112)

Abstract

Tuberculosis, caused by Mycobacterium tuberculosis, has re-emerged as a threat to human race. Conventional antibiotic treatments are failing due to different stress response strategies adopted by bacterial pathogens. Since time immemorial, Vitamin C is known to protect against pathogens by boosting immunity in humans. Recently, Vitamin C has been shown to directly kill M. tuberculosis including multiple drug-resistant strains by generation of oxidative radicals through Fenton’s reaction. Concurrently, it inhibits (p)ppGpp-mediated stringent response thus effectively shutting down long-term survival and persistence in mycobacteria. Here, we have discussed historical perspective and recent evidences on Vitamin C-mediated inhibition of several key pathways of M. tuberculosis such as (p)ppGpp synthesis and mycobacterial cell wall function. Several cell wall components including mycolic acids are critical for mycobacterial virulence. We observed downregulation of various mycolic acids in M. smegmatis upon treatment with Vitamin C, and data have been presented here. Vitamin C has been shown to inhibit the biofilm growth as well as disrupt the formed biofilm in mycobacteria. Additionally, Vitamin C role in cell-mediated and humoral immunity has been elucidated. Vitamin C is toxic at high concentration; therefore we have proposed the idea of derivatizing Vitamin C in order to lower the minimal inhibition concentration (MIC) necessary to target M. tuberculosis.

Keywords

Vitamin C (p)ppGpp Biofilm formation Immune response Oxidative radicals Mycobacteria Mycolic acid 

Abbreviations

(p)ppGpp

Guanosine tetraphosphate or guanosine pentaphosphate

C1q

Complement component 1, q subcomponent

MDR

Multidrug resistant

NK cells

Natural killer cells

RF3

Release factor 3

RNAP or RNA Pol

RNA polymerase

RNS

Reactive nitrogen species

ROS

Reactive oxygen species

TLC

Thin-layer chromatography

XDR

Extensively drug resistant

Notes

Acknowledgement

Authors acknowledge the Department of Science and Technology, Government of India, and Department of Biotechnology, Government of India, for funding the laboratory.

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© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Molecular Biophysics UnitIndian Institute of ScienceBangaloreIndia

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