Usefulness of Mycobacterium tuberculosis genomic mutations in the genes katG and inhA for the prediction of isoniazid resistance.
METHODS
Mutations in two genes of Mycobacterium tuberculosis, inhA and katG, are known to correlate with resistance to isoniazid (INH).


OBJECTIVE
To determine which mutation or mutations are the most predictive for INH resistance and the most frequent ones in such isolates. Further, to propose a simple and generally applicable method for their detection.


METHODS
Codons 94 and 95 in the inhA gene and codons 315 and 463 in the katG gene were characterized in 50 INH-resistant and 12 INH-sensitive isolates from Germany and Sierra Leone.


RESULTS
Mutations in codon 315 of the katG gene were detected in 27 of the INH-resistant and none of the INH-sensitive isolates. All mutations in this codon altered an AciI restriction enzyme site. No mutations were found in the investigated codons of the inhA gene.


CONCLUSIONS
We propose that most INH resistances can be rapidly predicted by a simple AciI restriction enzyme digest of a polymerase chain reaction (PCR)-amplified katG fragment.
Dobner
P
P
Department of Infectious Diseases and Tropical Medicine, University of Munich, Germany.
Rüsch-Gerdes
S
S
Bretzel
G
G
Feldmann
K
K
Rifai
M
M
Löscher
T
T
Rinder
H
H
D000995:Antitubercular Agents / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000235:genetics*; D003062:Codon / Q000235:genetics; D003431:Cross-Cultural Comparison; D004252:DNA Mutational Analysis; D005858:Germany; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use*; D016297:Mutagenesis, Site-Directed; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics*; D010088:Oxidoreductases; D010544:Peroxidases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012807:Sierra Leone; D018088:Tuberculosis, Multidrug-Resistant / Q000382:microbiology*
D000995:Antitubercular Agents; D001426:Bacterial Proteins; D003062:Codon; D010088:Oxidoreductases; D010544:Peroxidases; C076136:catalase HPI; C085257:InhA protein, Mycobacterium; D007538:Isoniazid