Article Figures & Data
Tables
- Table 1.
MICs for K. pneumoniae clinical isolates Kp 395 and Kp 377 and E. coli strains producing TEM-18, TEM-2, or TEM-3
Strain or β-lactamase produced MIC (μg/ml)a AMX TIC PIP CFT FOX ATM CTX CAZ K. pneumoniae Kp 395 (TEM-56) >8,192 (1,024) >8,192 (1,024) >2,048 (16) 512 4 (4) 1 (0.25) 0.25 (≤0.06) 4 (2) Kp 377 (TEM-21) >8,192 (32) >8,192 (16) 1,024 (4) 256 4 (4) 16 (0.12) 128 (≤0.06) 32 (1) E. coli TEM-18 8,192 (512) 1,024 (64) 512 (16) 16 8 (8) 2 (1) 0.25 (0.12) 4 (2) TEM-3 8,192 (16) 8,192 (32) 256 (2) 128 4 (4) 8 (0.5) 64 (0.12) 32 (0.5) TEM-2 4,096 (16) 4,096 (32) 512 (2) 32 2 (2) ≤0.06 (≤0.06) ≤0.06 (≤0.06) 0.5 (0.25) ↵a AMX, amoxicillin; TIC, ticarcillin; PIP, piperacillin; CFT, cephalothin; FOX, cefoxitin; ATM, aztreonam; CTX, cefotaxime; CAZ, ceftazidime. The values in parentheses are MICs in the presence of 2 μg/ml of clavulanic acid.
- Table 2.
Nucleotide substitutions inbla TEM-2, bla TEM-21, and bla TEM-56 genes
Region and nucleotide positiona Nucleotide in: blaTEM-2 blaTEM-21 blaTEM-56 Promoter region 32* b T T T 175* A A A Coding region 226* C C C 317* A (Lys-39c) A A 346* G G G 436* T T T 512 G (Glu-104) A (Lysd) A (Lys) 604* G G G 660 A (His-153) G (Arg) G (Arg) 682* C C C 914 G (Gly-238) A (Ser) G 925* A A A ↵a Nucleotide numbering is according to that given by Sutcliffe (23) and amino acid numbering is according to Ambler et al. (1).
↵b Nucleotides marked with an asterisk are involved in the differences between bla TEM-2,bla TEM-1A, and bla TEM-1Bgenes (9, 10, 23).
↵c Gln for TEM-1.
↵d For TEM-21 and TEM-56, there are indicated amino acids differing from TEM-2.
- Table 3.
Comparative kinetic parameters of β-lactamase TEM-2 and its mutants
Drug Kinetic parameters ofa: TEM-2 TEM-18 TEM-56 TEM-3 TEM-21 kcat Km kcat/Km kcat Km kcat/Km kcat Km kcat/Km kcat Km kcat/Km kcat Km kcat/Km Benzylpenicillin 1,500 18 83 1,400 24 58 1,400 22 63 45 6 7.5 50 9 5.5 Amoxicillin 1,200 20 60 1,300 41 31.7 1,330 40 33 31 5 6.2 43 20 2.15 Ticarcillin 195 12 16.2 280 6 47 300 7 43 9 2 4.5 7 3 2.3 Piperacillin 1,275 40 31.8 1,360 40 34 1,350 38 35 72 12 6 46 12 3.8 Cephalothin 300 350 0.86 225 135 1.7 250 140 1.8 48 23 2.1 18 55 0.33 Cephaloridine 825 800 1.0 1,360 1,200 1.1 1,350 1,200 1.1 43 30 1.4 120 120 1.0 Cefoperazone 700 230 3.0 550 170 3.2 550 180 3.0 28 20 1.4 19 30 0.63 Cefuroxime 3 1,000 <0.01 10 480 0.02 8 470 0.02 28 90 0.31 18 85 0.21 Ceftriaxone <1 ND <0.01 21 800 0.03 16 840 0.02 81 80 1 53 210 0.25 Cefotaxime 1.5 ND <0.01 35 1,660 0.02 28 1,700 0.02 202 100 2 120 400 0.3 Ceftazidime <1 ND <0.01 <1 ND <0.01 <1 ND <0.01 18 200 0.1 4 ND <0.01 ↵a kcat values are given in per second units, Km values are given in micromolar units, and kcat/Km values are given in per micromole per second units. The values given forkcat and Km were computed on the basis of at least three independent experiments. ND, not detected (high Km or Ki values).
- Table 4.
50% inhibitory concentrations (IC50s) of β-lactamase inhibitors for β-lactamase TEM-2 and its mutants
β-Lactamase IC50 (μM) of: Clavulanic acid Sulbactam Tazobactam TEM-2 0.16 8 0.1 TEM-18 0.007 4.2 0.1 TEM-56 0.008 4.3 0.1 TEM-3 0.01 0.4 0.01 TEM-21 0.01 2 0.07
