Expression of katG in Mycobacterium tuberculosis is associated with its growth and persistence in mice and guinea pigs.
The molecular mechanisms associated with the pathogenesis of tuberculosis are not well understood. The present study evaluated the role of catalase-peroxidase as a potential virulence factor for Mycobacterium tuberculosis. Growth and persistence of M. tuberculosis H37Rv in intravenously infected BALB/ c mice were compared with katG-deleted, isoniazid-resistant M. tuberculosis H37RVINHR. Transformation of M. tuberculosis H37Rv (TBkatG) or Mycobacterium intracellulare (MACkatG) genes into M. tuberculosis H37RvINHR restored its catalase-peroxidase activities and the ability of the recombinants to persist in spleens of mice and guinea pigs. Transformation with the TBkatG gene with the codon 463 R-->L mutation also restored catalase-peroxidase activity and enhanced persistence. However, transformants with the codon 275 T-->P mutant expressed low levels of enzymatic activity and failed to persist in guinea pig spleen, although they did survive in mouse tissues. These results indicate that KatG contributes to the ability of M. tuberculosis to grow and survive within the infected host tissues.
Li
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Z
Laboratory of Mycobacteria, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA.
Kelley
C
C
Collins
F
F
Rouse
D
D
Morris
S
S
D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology; D001426:Bacterial Proteins; D002908:Chronic Disease; D003062:Codon; D015169:Colony Count, Microbial; D004269:DNA, Bacterial / Q000235:genetics; D004352:Drug Resistance, Microbial / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006168:Guinea Pigs; D007538:Isoniazid / Q000494:pharmacology; D008168:Lung / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D015269:Mycobacterium avium Complex / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D010544:Peroxidases / Q000235:genetics* / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D017384:Sequence Deletion; D013154:Spleen / Q000382:microbiology; D014170:Transformation, Genetic; D014376:Tuberculosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D014774:Virulence / Q000235:genetics
D000995:Antitubercular Agents; D001426:Bacterial Proteins; D003062:Codon; D004269:DNA, Bacterial; D010544:Peroxidases; C076136:catalase HPI; D007538:Isoniazid