Overproduction of mycobacterial ribosomal protein S13 induces catalase/peroxidase activity and hypersensitivity to isoniazid in Mycobacterium smegmatis.
A Bacillus Calmette Guerlin (BCG) DNA fragment was identified which conferred hypersensitivity to isoniazid (INH) upon Mycobacterium smegmatis (Ms) when present on a multicopy plasmid. The gene cluster present on this fragment contains the genes encoding ribosomal proteins L36 (rpmJ), S13 (rpsM), S11 (rpsK) and S4 (rpsD), as well as the gene encoding initiation factor-1 (infA), an open reading frame of unknown function (ORFX) and a putative promoter region. The rpsM gene, from either BCG or Ms is necessary and sufficient to produce the INH-hypersensitive phenotype in Ms, but the gene cluster has no effect on INH sensitivity when introduced into BCG on a multicopy plasmid. The presence of rpsM on a multicopy plasmid also causes an increase in catalase/peroxidase (Kat/Prx) activity in Ms. The overproduction of S13 may induce a stress response, resulting in increased expression of katG (encoding Kat/Prx) in Ms, thereby causing hypersensitivity to INH.
Dubnau
E
E
Public Health Research Institute, Tuberculosis Center, New York, NY 10016, USA.
Soares
S
S
Huang
T J
TJ
Jacobs
W R
WR
D000595:Amino Acid Sequence; D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins; D002374:Catalase / Q000096:biosynthesis* / Q000235:genetics; D004352:Drug Resistance, Microbial / Q000235:genetics; D004790:Enzyme Induction; D015964:Gene Expression Regulation, Bacterial; D007538:Isoniazid / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009161:Mycobacterium / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009163:Mycobacterium bovis / Q000235:genetics*; D010544:Peroxidases / Q000096:biosynthesis* / Q000235:genetics; D010641:Phenotype; D010957:Plasmids / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis; D012269:Ribosomal Proteins / Q000096:biosynthesis* / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D000995:Antitubercular Agents; D001426:Bacterial Proteins; D011994:Recombinant Proteins; D012269:Ribosomal Proteins; D010544:Peroxidases; D002374:Catalase; C076136:catalase HPI; D007538:Isoniazid