Disparate Responses to Oxidative Stress in Saprophytic and Pathogenic Mycobacteria

• Published in: Proceedings of the National Academy of Sciences - PNAS 1995-07, Vol.92 (14), p.6625-6629
• Main Authors: Sherman, D R, Sabo, P J, Hickey, M J, Arain, T M, Mahairas, G G, Yuan, Y, Barry, 3rd, C E, Stover, C K
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Autoradiography; Bacteria; Bacterial Proteins - biosynthesis; Bacterial Proteins - genetics; Base Sequence; Biology; Cattle; Disease; DNA, Bacterial - chemistry; DNA, Bacterial - genetics; DNA-Binding Proteins; Gene Expression; Genes; Genes, Bacterial; Genetic loci; Gram negative bacteria; Granuloma - microbiology; Humans; Hydrogen; Macrophages - microbiology; Methionine - metabolism; Molecular Sequence Data; Mycobacterium - genetics; Mycobacterium - pathogenicity; Mycobacterium - physiology; Mycobacterium avium - genetics; Mycobacterium avium - pathogenicity; Mycobacterium avium - physiology; Mycobacterium bovis - genetics; Mycobacterium bovis - pathogenicity; Mycobacterium bovis - physiology; Mycobacterium smegmatis; Mycobacterium tuberculosis; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - pathogenicity; Mycobacterium tuberculosis - physiology; Oligodeoxyribonucleotides; Open reading frames; Oxidative Stress; Oxidoreductases - biosynthesis; Oxidoreductases - genetics; Oxygen; Peroxidases; Peroxides; Peroxiredoxins; Proteins; Repressor Proteins - genetics; Sequence Homology, Amino Acid; Species Specificity; Sulfur Radioisotopes; Toxicity; Transcription Factors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.14.6625

To persist in macrophages and in granulomatous caseous lesions, pathogenic mycobacteria must be equipped to withstand the action of toxic oxygen metabolites. In Gram-negative bacteria, the OxyR protein is a critical component of the oxidative stress response. OxyR is both a sensor of reactive oxygen species and a transcriptional activator, inducing expression of detoxifying enzymes such as catalase/hydroperoxidase and alkyl hydroperoxidase. We have characterized the responses of various mycobacteria to hydrogen peroxide both phenotypically and at the levels of gene and protein expression. Only the saprophytic Mycobacterium smegmatis induced a protective oxidative stress response analogous to the OxyR response of Gram-negative bacteria. Under similar conditions, the pathogenic mycobacteria exhibited a limited, nonprotective response, which in the case of Mycobacterium tuberculosis was restricted to induction of a single protein, KatG. We have also isolated DNA sequences homologous to oxyR and ahpC from M. tuberculosis and Mycobacterium avium. While the M. avium oxyR appears intact, the oxyR homologue of M. tuberculosis contains numerous deletions and frameshifts and is probably nonfunctional. Apparently the response of pathogenic mycobacteria to oxidative stress differs significantly from the inducible OxyR response of other bacteria.