TABLE 1.

Resistance mutations in the atpE gene and MIC levelsa

Parent strain group and strainSelection concn (multiple of MIC)No. of mutants sequenced (total no. obtained)atpE, F0 operon, or ATP synthase operon mutationNo. of independent mutantsMIC range (mg/liter)
MDR parent strains
    1106 (12)Glu61 → Asp (GAG-GAC)10.48
WT atpE50.12-0.48
302 (2)Ala63 → Pro (GCA-CCA)21.92-3.84
    2103 (5)Asp28 → Val (GAC-GTC)10.48
Glu61 → Asp (GAG-GAC)10.24
WT atpE10.12
300 (0)
    3106 (12)WT atpE20.9
WT atpE and F0 operon10.9
WT atpE and ATP synthase30.9
305 (11)WT atpE30.48-0.9
WT atpE and F0 operon20.9
    5103 (7)WT atpE20.12-0.24
WT atpE and F0 operon10.24
302 (2)Ala63 → Pro (GCA-CCA)10.9
Ile66 → Met (ATC-ATG)10.48
Drug-susceptible parent strains
    4107 (12)Asp28 → Pro (GAC-GGC)10.3
Glu61 → Asp (GAG-GAC)10.96
WT atpE30.12-0.24
WT atpE and F0 operon20.3-0.48
301 (1)Glu61 → Asp (GAG-GAC)10.48
    6105 (10)WT atpE50.24-0.96
305 (5)Glu61 → Asp (GAG-GAC)10.48
Ala63 → Pro (GCA-CCA)10.9
WT atpE30.12-24
    7103 (10)WT atpE10.48
WT atpE and F0 operon20.48
305 (5)Ala63 → Pro (GCA-CCA)33.84
WT atpE20.24-0.48
  • a The atpE genes of 53 mutants (33 selected at 10× MIC [0.3 mg/liter] and 20 selected at 30× MIC [0.9 mg/liter]) were sequenced, and six different classes of mutations were identified. The first five classes represented single point mutations within the atpE gene; and the last group, which consisted of 38 mutant clones, represented mutants in which no mutation within the sequenced gene was identified. Eleven of the mutants exhibited wild-type (WT) F0 operons, and three of these had wild-type ATP synthase (F0 and F1 operons).