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PMID: 9733688 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Oxidative stress response and characterization of the oxyR-ahpC and furA-katG loci in Mycobacterium marinum.

Journal of bacteriology ·Vol. 180 ·No. 18 ·1998-09-00 ·Pages 4856-64

Pagán-Ramos E, Song J, McFalone M, Mudd MH, Deretic V

Abstract

Oxidative stress response in pathogenic mycobacteria is believed to be of significance for host-pathogen interactions at various stages of infection. It also plays a role in determining the intrinsic susceptibility to isoniazid in mycobacterial species. In this work, we characterized the oxyR-ahpC and furA-katG loci in the nontuberculous pathogen Mycobacterium marinum. In contrast to Mycobacterium smegmatis and like Mycobacterium tuberculosis and Mycobacterium leprae, M. marinum was shown to possess a closely linked and divergently oriented equivalents of the regulator of peroxide stress response oxyR and its subordinate gene ahpC, encoding a homolog of alkyl hydroperoxide reductase. Purified mycobacterial OxyR was found to bind to the oxyR-ahpC promoter region from M. marinum and additional mycobacterial species. Mobility shift DNA binding analyses using OxyR binding sites from several mycobacteria and a panel of in vitro-generated mutants validated the proposed consensus mycobacterial recognition sequence. M. marinum AhpC levels detected by immunoblotting, were increased upon treatment with H2O2, in keeping with the presence of a functional OxyR and its binding site within the promoter region of ahpC. In contrast, OxyR did not bind to the sequences upstream of the katG structural gene, and katG expression did not follow the pattern seen with ahpC. Instead, a new open reading frame encoding a homolog of the ferric uptake regulator Fur was identified immediately upstream of katG in M. marinum. The furA-katG linkage and arrangement are ubiquitous in mycobacteria, suggesting the presence of additional regulators of oxidative stress response and potentially explaining the observed differences in ahpC and katG expression. Collectively, these findings broaden our understanding of oxidative stress response in mycobacteria. They also suggest that M. marinum will be useful as a model system for studying the role of oxidative stress response in mycobacterial physiology, intracellular survival, and other host-pathogen interactions associated with mycobacterial diseases.

MeSH Terms
Amino Acid Sequence Animals Bacterial Proteins/genetics Cell Line Chromosome Mapping DNA-Binding Proteins Genes, Bacterial Mice Molecular Sequence Data Mycobacterium marinum/genetics,metabolism Oxidative Stress Oxidoreductases/genetics Peroxidases/genetics Peroxiredoxins Rabbits Repressor Proteins/genetics Transcription Factors/genetics
Chemicals
Bacterial Proteins DNA-Binding Proteins Repressor Proteins Transcription Factors ferric uptake regulating proteins, bacterial Oxidoreductases Peroxidases Peroxiredoxins catalase HPI
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Pagán-Ramos E
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0620, USA.
Song J
McFalone M
Mudd M H
Deretic V
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Article Info
Journal
Journal of bacteriology
Abbr.
J Bacteriol
ISSN
0021-9193
DOI
10.1128/JB.180.18.4856-4864.1998
Published
1998-09-00
Pages
4856-64
Language
English
Region
United States
NLM ID
2985120R
PMCID
PMC107510
Subset
IM
Grants
NIAID NIH HHS · AI04299 · United States
NIAID NIH HHS · AI25217 · United States
Databases
GENBANK
AF034861, AF038027, U43810
External Links
PubMed source DOI: 10.1128/JB.180.18.4856-4864.1998 PMC Full Text View journal details
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