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PMID: 8665467 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S. Review

Antimicrobial agent resistance in mycobacteria: molecular genetic insights.

Clinical microbiology reviews ·Vol. 8 ·No. 4 ·1995-10-00 ·Pages 496-514

Musser JM

Abstract

The primary theme emerging from molecular genetic work conducted with Mycobacterium tuberculosis and several other mycobacterial species is that resistance is commonly associated with simple nucleotide alterations in target chromosomal genes rather than with acquisition of new genetic elements encoding antibiotic-altering enzymes. Mutations in an 81-bp region of the gene (rpoB) encoding the beta subunit of RNA polymerase account for rifampin resistance in 96% of M. tuberculosis and many Mycobacterium leprae isolates. Streptomycin resistance in about one-half of M. tuberculosis isolates is associated with missense mutations in the rpsL gene coding for ribosomal protein S12 or nucleotide substitutions in the 16S rRNA gene (rrs). Mutations in the katG gene resulting in catalase-peroxidase amino acid alterations nad nucleotide substitutions in the presumed regulatory region of the inhA locus are repeatedly associated with isoniazid-resistant M. tuberculosis isolates. A majority of fluoroquinolone-resistant M. tuberculosis isolates have amino acid substitutions in a region of the DNA gyrase A subunit homologous to a conserved fluoroquinolone resistance-determining region. Multidrug-resistant isolates of M. tuberculosis arise as a consequence of sequential accumulation of mutations conferring resistance to single therapeutic agents. Molecular strategies show considerable promise for rapid detection of mutations associated with antimicrobial resistance. These approaches are now amenable to utilization in an appropriately equipped clinical microbiology laboratory.

MeSH Terms
Amino Acid Sequence Anti-Infective Agents/pharmacology Antibiotics, Antitubercular/pharmacology Base Sequence Drug Resistance, Microbial/genetics Fluoroquinolones Genes, Bacterial/genetics Isoniazid/pharmacology Molecular Sequence Data Mutation/genetics Mycobacterium/drug effects,genetics
Chemicals
Anti-Infective Agents Antibiotics, Antitubercular Fluoroquinolones Isoniazid
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Musser J M
Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA.
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Article Info
Journal
Clinical microbiology reviews
Abbr.
Clin Microbiol Rev
ISSN
0893-8512
DOI
10.1128/CMR.8.4.496
Published
1995-10-00
Pages
496-514
Language
English
Region
United States
NLM ID
8807282
PMCID
PMC172873
Subset
IM
Grants
NIAID NIH HHS · AI-37004 · United States
NIDA NIH HHS · DA/AI-09238 · United States
Databases
GENBANK
L05910, L27512, L27989, U02492, X52917, X68081, X70995
External Links
PubMed source DOI: 10.1128/CMR.8.4.496 PMC Full Text View journal details
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