Disparate responses to oxidative stress in saprophytic and pathogenic mycobacteria.
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.
Sherman
D R
DR
Laboratory of Tuberculosis and Molecular Microbiology, PathoGenesis Corporation, Seattle, WA 98119, USA.
Sabo
P J
PJ
Hickey
M J
MJ
Arain
T M
TM
Mahairas
G G
GG
Yuan
Y
Y
Barry
C E
CE
Stover
C K
CK
D000595:Amino Acid Sequence; D000818:Animals; D001345:Autoradiography; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D001483:Base Sequence; D002417:Cattle; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics*; D004268:DNA-Binding Proteins; D015870:Gene Expression; D005798:Genes, Bacterial; D006099:Granuloma / Q000382:microbiology; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D008715:Methionine / Q000378:metabolism; D008969:Molecular Sequence Data; D009161:Mycobacterium / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D009162:Mycobacterium avium / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D009163:Mycobacterium bovis / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D009838:Oligodeoxyribonucleotides; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000096:biosynthesis / Q000235:genetics; D010544:Peroxidases; D054464:Peroxiredoxins; D011506:Proteins; D012097:Repressor Proteins / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013462:Sulfur Radioisotopes; D014157:Transcription Factors
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D011506:Proteins; D012097:Repressor Proteins; D013462:Sulfur Radioisotopes; D014157:Transcription Factors; D008715:Methionine; D010088:Oxidoreductases; D010544:Peroxidases; D054464:Peroxiredoxins