Frequency of embB codon 306 mutations in ethambutol-susceptible and -resistant clinical Mycobacterium tuberculosis isolates in Kuwait.
METHODS
Recent reports of embB306 mutations in ethambutol-resistant and ethambutol-susceptible drug-resistant strains of Mycobacterium tuberculosis have questioned the significance of these mutations in conferring resistance to ethambutol (EMB).


OBJECTIVE
To determine the occurrence of embB306 mutations in all EMB-resistant and -susceptible drug-resistant M. tuberculosis strains isolated during a specified period at a single geographical location.


METHODS
Twenty-five pansusceptible, all EMB-resistant and -susceptible M. tuberculosis strains resistant to other first-line drugs isolated in Kuwait during 2000-2003 were analyzed. The embB306 mutations were detected by PCR-restriction fragment length polymorphism and DNA sequencing. The PCR-based methods were also used for determining strain relatedness.


RESULTS
None of the pansusceptible M. tuberculosis strains contained a mutation at embB306. Fifteen of 50 (30%) EMB-resistant strains but only three of 122 (2%) EMB-susceptible isolates resistant to other first-line drugs contained a mutated embB306. The EMB-susceptible isolates with embB306 mutation were resistant to isoniazid plus other drug(s). The isolates carrying similar mutations were genotypically distinct strains.


CONCLUSIONS
The frequency of embB306 mutations in EMB-resistant strains compared to EMB-susceptible M. tuberculosis isolates resistant to other drugs was 15 times higher. Association of embB306 mutations in EMB-susceptible strains with isoniazid resistance and inherent problems associated with phenotypic EMB susceptibility testing suggest that these strains may actually be EMB-resistant.
Ahmad
S
S
Department of Microbiology, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait. suhail_ah@hsc.edu.kw
Jaber
A-A
AA
Mokaddas
E
E
D000995:Antitubercular Agents / Q000494:pharmacology*; D001483:Base Sequence; D003062:Codon / Q000235:genetics*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004977:Ethambutol / Q000494:pharmacology*; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology; D007730:Kuwait / Q000453:epidemiology; D008826:Microbial Sensitivity Tests / Q000379:methods; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D014397:Tuberculosis, Pulmonary / Q000453:epidemiology / Q000382:microbiology
D000995:Antitubercular Agents; D003062:Codon; D004977:Ethambutol; D007538:Isoniazid