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The Physiology and Genetics of Oxidative Stress in Mycobacteria

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  • Authors: Bridgette M. Cumming1, Dirk A. Lamprecht2, Ryan M. Wells3, Vikram Saini5, James H. Mazorodze6, Adrie J. C. Steyn7
  • Editors: Graham F. Hatfull9, William R. Jacobs Jr.10
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Durban, South Africa; 2: KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Durban, South Africa; 3: KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Durban, South Africa; 4: Department of Microbiology, University of Alabama at Birmingham, AL 35294; 5: Department of Microbiology, University of Alabama at Birmingham, AL 35294; 6: KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Durban, South Africa; 7: KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Durban, South Africa; 8: Department of Microbiology, University of Alabama at Birmingham, AL 35294; 9: University of Pittsburgh, Pittsburgh, PA; 10: Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY
  • Source: microbiolspec May 2014 vol. 2 no. 3 doi:10.1128/microbiolspec.MGM2-0019-2013
  • Received 10 June 2013 Accepted 26 July 2013 Published 02 May 2014
  • Adrie JC Steyn, asteyn@uab.edu and adrie.steyn@k-rith.org
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  • Abstract:

    During infection, is exposed to a diverse array of microenvironments in the human host, each with its own unique set of redox conditions. Imbalances in the redox environment of the bacillus or the host environment serve as stimuli, which could regulate virulence. The ability of to evade the host immune response and cause disease is largely owing to the capacity of the mycobacterium to sense changes in its environment, such as host-generated gases, carbon sources, and pathological conditions, and alter its metabolism and redox balance accordingly for survival. In this article we discuss the redox sensors that are, to date, known to be present in , such as the Dos dormancy regulon, WhiB family, anti-σ factors, and MosR, in addition to the strategies present in the bacillus to neutralize free radicals, such as superoxide dismutases, catalase-peroxidase, thioredoxins, and methionine sulfoxide reductases, among others. is peculiar in that it appears to have a hierarchy of redox buffers, namely, mycothiol and ergothioneine. We discuss the current knowledge of their biosynthesis, function, and regulation. Ergothioneine is still an enigma, although it appears to have distinct and overlapping functions with mycothiol, which enable it to protect against a wide range of toxic metabolites and free radicals generated by the host. Developing approaches to quantify the intracellular redox status of the mycobacterium will enable us to determine how the redox balance is altered in response to signals and environments that mimic those encountered in the host.

  • Citation: Cumming B, Lamprecht D, Wells R, Saini V, Mazorodze J, Steyn A. 2014. The Physiology and Genetics of Oxidative Stress in Mycobacteria. Microbiol Spectrum 2(3):MGM2-0019-2013. doi:10.1128/microbiolspec.MGM2-0019-2013.

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/content/journal/microbiolspec/10.1128/microbiolspec.MGM2-0019-2013
2014-05-02
2017-09-25

Abstract:

During infection, is exposed to a diverse array of microenvironments in the human host, each with its own unique set of redox conditions. Imbalances in the redox environment of the bacillus or the host environment serve as stimuli, which could regulate virulence. The ability of to evade the host immune response and cause disease is largely owing to the capacity of the mycobacterium to sense changes in its environment, such as host-generated gases, carbon sources, and pathological conditions, and alter its metabolism and redox balance accordingly for survival. In this article we discuss the redox sensors that are, to date, known to be present in , such as the Dos dormancy regulon, WhiB family, anti-σ factors, and MosR, in addition to the strategies present in the bacillus to neutralize free radicals, such as superoxide dismutases, catalase-peroxidase, thioredoxins, and methionine sulfoxide reductases, among others. is peculiar in that it appears to have a hierarchy of redox buffers, namely, mycothiol and ergothioneine. We discuss the current knowledge of their biosynthesis, function, and regulation. Ergothioneine is still an enigma, although it appears to have distinct and overlapping functions with mycothiol, which enable it to protect against a wide range of toxic metabolites and free radicals generated by the host. Developing approaches to quantify the intracellular redox status of the mycobacterium will enable us to determine how the redox balance is altered in response to signals and environments that mimic those encountered in the host.

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Figures

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FIGURE 1

The RSH/RSSR reductase/NAD(P)H redox pathway for the reduction of cellular oxidants. The oxidation-reduction reaction of a typical flavoprotein disulfide reductase. The commonly found intracellular low-molecular-weight thiols and the organisms in which they are found. doi:10.1128/microbiolspec.MGM2-0019-2013.f1

Source: microbiolspec May 2014 vol. 2 no. 3 doi:10.1128/microbiolspec.MGM2-0019-2013
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FIGURE 2

The biosynthesis pathway of mycothiol (MSH), with the related biosynthesis of I-1-P by tbINO. The enzyme associated with MshA2 activity is yet to be identified. The genomic organization of the MSH biosynthetic genes in H37Rv. See text for definition of abbreviations. doi:10.1128/microbiolspec.MGM2-0019-2013.f2

Source: microbiolspec May 2014 vol. 2 no. 3 doi:10.1128/microbiolspec.MGM2-0019-2013
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FIGURE 3

The intracellular functions of MSH: redox homeostasis, detoxification, source of carbon, and a cofactor in enzyme reactions. doi:10.1128/microbiolspec.MGM2-0019-2013.f3

Source: microbiolspec May 2014 vol. 2 no. 3 doi:10.1128/microbiolspec.MGM2-0019-2013
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FIGURE 4

Biosynthesis of ergothioneine as proposed by Seebeck ( 179 ). Putative five-gene cluster in H37Rv encoding ERG biosynthetic enzymes. doi:10.1128/microbiolspec.MGM2-0019-2013.f4

Source: microbiolspec May 2014 vol. 2 no. 3 doi:10.1128/microbiolspec.MGM2-0019-2013
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Tables

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TABLE 1

Mycothiol biosynthetic enzyme knockouts

Source: microbiolspec May 2014 vol. 2 no. 3 doi:10.1128/microbiolspec.MGM2-0019-2013

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