Resistance to D-cycloserine in the tubercle bacilli: mutation rate and transport of alanine in parental cells and drug-resistant mutants.
A single transport system was found to accumulate l- and d-alanine, glycine and d-serine in Mycobacterium tuberculosis. The results of inhibition experiments suggested that the antibiotics d-cycloserine and O-carbamyl-d-serine were also transported by the alanine-glycine-d-serine system. A d-cycloserine-resistant permease-competent (d-CS(r)/perm(+)) mutant and a d-cycloserine-resistant permease-defective (d-CS(r)/perm(-)) mutant were isolated. The d-CS(r)/perm(-) mutant was not found to be more resistant to the drug than was the d-CS(r)/perm(+) mutant. The data were consistent with the conclusion that resistance to d-cycloserine in the tubercle bacilli is primarily due to mutations in the gene(s) controlling the enzyme d-alanyl-d-alanine synthetase. The mutation rate was calculated to be about 10(-10) mutations per bacterium per generation.
D000409:Alanine / Q000378:metabolism*; D002219:Carbamates / Q000378:metabolism / Q000494:pharmacology; D002247:Carbon Isotopes; D003523:Cycloserine / Q000378:metabolism / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D005827:Genetics, Microbial; D005998:Glycine / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification; D012694:Serine / Q000378:metabolism / Q000494:pharmacology
D002219:Carbamates; D002247:Carbon Isotopes; D026901:Membrane Transport Proteins; D012694:Serine; D003523:Cycloserine; D000409:Alanine; D005998:Glycine