| Mutation of tlyA confers capreomycin resistance in Mycobacterium tuberculosis. | |
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MedLine Citation:
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PMID: 15673735 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Capreomycin, an important drug for the treatment of multidrug-resistant tuberculosis, is a macrocyclic peptide antibiotic produced by Saccharothrix mutabolis subspecies capreolus. The basis of resistance to this drug was investigated by isolating and characterizing capreomycin-resistant strains of Mycobacterium smegmatis and Mycobacterium tuberculosis. Colonies resistant to capreomycin were recovered from a library of transposon-mutagenized M. smegmatis. The transposon insertion site of one mutant was mapped to an open reading frame in the unfinished M. smegmatis genome corresponding to the tlyA gene (Rv1694) in the M. tuberculosis H37Rv genome. In M. smegmatis spontaneous capreomycin-resistant mutants, the tlyA gene was disrupted by one of three different naturally occurring insertion elements. Genomic DNAs from pools of transposon mutants of M. tuberculosis H37Rv were screened by PCR by using primers to the tlyA gene and the transposon to detect mutants with an insertion in the tlyA gene. One capreomycin-resistant mutant was recovered that contained the transposon inserted at base 644 of the tlyA gene. Complementation with the wild-type tlyA gene restored susceptibility to capreomycin in the M. smegmatis and M. tuberculosis tlyA transposon mutants. Mutations were found in the tlyA genes of 28 spontaneous capreomycin-resistant mutants generated from three different M. tuberculosis strains and in the tlyA genes of capreomycin-resistant clinical isolates. In in vitro transcription-translation assays, ribosomes from tlyA mutant but not tlyA(+) strains resist capreomycin inhibition of transcription-translation. Therefore, TlyA appears to affect the ribosome, and mutation of tlyA confers capreomycin resistance. |
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Authors:
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Courtney E Maus; Bonnie B Plikaytis; Thomas M Shinnick |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Antimicrobial agents and chemotherapy Volume: 49 ISSN: 0066-4804 ISO Abbreviation: Antimicrob. Agents Chemother. Publication Date: 2005 Feb |
Date Detail:
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Created Date: 2005-01-27 Completed Date: 2005-03-29 Revised Date: 2013-04-18 |
Medline Journal Info:
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Nlm Unique ID: 0315061 Medline TA: Antimicrob Agents Chemother Country: United States |
Other Details:
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Languages: eng Pagination: 571-7 Citation Subset: IM |
Affiliation:
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Program in Microbiology and Molecular Genetics, Emory University, Atlanta, Georgia, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antibiotics, Antitubercular
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pharmacology* Bacterial Proteins / genetics* Blotting, Southern Capreomycin / pharmacology* Cloning, Molecular DNA Transposable Elements / genetics DNA, Bacterial / biosynthesis, genetics Drug Resistance, Bacterial Gene Library Hemolysin Proteins / genetics* Humans Microbial Sensitivity Tests Mutagenesis Mutation / genetics* Mycobacterium smegmatis / drug effects, genetics Mycobacterium tuberculosis / drug effects*, genetics* Plasmids Protein Biosynthesis RNA, Bacterial / genetics RNA, Ribosomal, 16S / genetics Reverse Transcriptase Polymerase Chain Reaction Transcription, Genetic Tuberculosis / microbiology Viomycin / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Antibiotics, Antitubercular; 0/Bacterial Proteins; 0/DNA Transposable Elements; 0/DNA, Bacterial; 0/Hemolysin Proteins; 0/RNA, Bacterial; 0/RNA, Ribosomal, 16S; 0/TlyA protein, Mycobacterium tuberculosis; 11003-38-6/Capreomycin; 32988-50-4/Viomycin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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