TABLE 1.
Susceptibility testing of recombinant E. coli MG1655 strains according to the PBP3 modification statusa
| Strain (β-lactamase produced) | β-Lactamase spectrum | Ambler class | Minimal inhibitory concentrations (µg/mL)b,c | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Ceftazidime | Ceftazidime-avibactam | Aztreonam | Aztreonam-avibactam | Cefepime | Cefepime-taniborbactam | |||||||||||||||
| E. coli ATCC25922 | – | – | 0.125 | 0.125 | ≤0.06 | ≤0.06 | ≤0.06 | ≤0.06 | ||||||||||||
| E. coli NCTC13353 | ESBL | A | >64 | 0.25 | >64 | ≤0.06 | >64 | 0.5 | ||||||||||||
| WT | YRIN | YRIK | WT | YRIN | YRIK | WT | YRIN | YRIK | WT | YRIN | YRIK | WT | YRIN | YRIK | WT | YRIN | YRIK | |||
| E. coli MG1655 | – | – | 0.125 | 0.5 | 0.5 | 0.125 | 0.5 | 0.5 | ≤0.06 | 1 | 1 | ≤0.06 | 1 | 1 | ≤0.06 | 0.5 | 0.5 | ≤0.06 | 0.25 | 0.25 |
| E. coli TEM-1 | Narrow | A | 0.125 | 0.5 | 0.5 | 0.125 | 0.5 | 0.5 | ≤0.06 | 1 | 1 | ≤0.06 | 1 | 1 | ≤0.06 | 0.5 | 0.5 | ≤0.06 | 0.25 | 0.25 |
| E. coli CTX-M-2 | ESBL | A | 0.5 | 2 | 2 | 0.125 | 0.5 | 0.5 | 0.25 | 4 | 4 | ≤0.06 | 1 | 1 | 0.5 | 1 | 1 | ≤0.06 | 0.25 | 0.25 |
| E. coli CTX-M-3 | ESBL | A | 4 | 32 | 32 | 0.125 | 1 | 1 | 4 | 64 | 64 | ≤0.06 | 1 | 1 | 4 | 64 | 64 | ≤0.06 | 0.25 | 0.25 |
| E. coli CTX-M-14 | ESBL | A | 1 | 4 | 4 | 0.125 | 0.5 | 0.5 | 4 | 64 | 64 | ≤0.06 | 1 | 1 | 4 | 32 | 32 | ≤0.06 | 0.25 | 0.25 |
| E. coli CTX-M-15 | ESBL | A | 256 | 2,048 | 2,048 | 0.5 | 8 | 8 | 1024 | >2,048 | >2,048 | ≤0.06 | 1 | 1 | 512 | >1,024 | >1,024 | 0.125 | 2 | 2 |
| E. coli CTX-M-33 | Carba | A | 16 | 64 | 64 | 0.25 | 2 | 2 | 64 | 1,024 | 1,024 | ≤0.06 | 1 | 1 | 128 | >1,024 | >1,024 | 0.125 | 1 | 1 |
| E. coli GES-1 | ESBL | A | 16 | 32 | 32 | 0.25 | 2 | 2 | 0.25 | 2 | 2 | ≤0.06 | 1 | 1 | 0.125 | 2 | 2 | ≤0.06 | 0.25 | 0.25 |
| E. coli GES-2 | Carba | A | 8 | 8 | 8 | 0.125 | 0.5 | 1 | 0.125 | 4 | 4 | ≤0.06 | 1 | 1 | 0.125 | 2 | 2 | ≤0.06 | 0.25 | 0.25 |
| E. coli GES-5 | Carba | A | 1 | 2 | 2 | 0.125 | 0.5 | 1 | ≤0.06 | 1 | 1 | ≤0.06 | 1 | 1 | ≤0.06 | 0.5 | 0.5 | ≤0.06 | 0.25 | 0.25 |
| E. coli GES-6 | Carba | A | 16 | 64 | 64 | 1 | 16 | 16 | 0.25 | 8 | 8 | ≤0.06 | 1 | 1 | ≤0.06 | 0.5 | 0.5 | ≤0.06 | 0.25 | 0.25 |
| E. coli BEL-1 | ESBL | A | 8 | 16 | 16 | 0.5 | 1 | 1 | 8 | 128 | 128 | 0.25 | 1 | 1 | 0.5 | 4 | 4 | ≤0.06 | 0.25 | 0.25 |
| E. coli SHV-1 | Narrow | A | 32 | 1,024 | 1,024 | 0.25 | 2 | 2 | 256 | >2,048 | >2,048 | ≤0.06 | 2 | 2 | 1 | 64 | 64 | ≤0.06 | 0.25 | 0.25 |
| E. coli SHV-2a | ESBL | A | 4 | 16 | 16 | 0.25 | 1 | 2 | 4 | 32 | 32 | ≤0.06 | 2 | 2 | 2 | 64 | 64 | ≤0.06 | 0.25 | 0.25 |
| E. coli SHV-12 | ESBL | A | 128 | 2,048 | 2,048 | 0.125 | 1 | 1 | 128 | >2,048 | >2,048 | 0.25 | 4 | 4 | 8 | 128 | 128 | ≤0.06 | 0.25 | 0.25 |
| E. coli VEB-1 | ESBL | A | 128 | 512 | 512 | 0.5 | 2 | 2 | 8 | 512 | 512 | ≤0.06 | 2 | 2 | 2 | 32 | 64 | ≤0.06 | 0.25 | 0.25 |
| E. coli FRI-1 | Carba | A | 1 | 4 | 4 | 0.25 | 1 | 1 | 512 | 2,048 | 2,048 | 0.5 | 8 | 8 | 0.125 | 1 | 1 | ≤0.06 | 0.25 | 0.25 |
| E. coli PER-1 | ESBL | A | 128 | 512 | 256 | 1 | 8 | 8 | 32 | 512 | 512 | 0.25 | 4 | 4 | 8 | 64 | 64 | ≤0.06 | 0.25 | 0.25 |
| E. coli PER-2 | ESBL | A | 256 | 1,024 | 1,024 | 2 | 16 | 16 | 128 | 2,048 | 2,048 | 2 | 16 | 16 | 8 | 64 | 64 | ≤0.06 | 0.25 | 0.25 |
| E. coli PER-6 | ESBL | A | >2,048 | >2,048 | >2,048 | 16 | 256 | 256 | 2,048 | >2,048 | >2,048 | 16 | 256 | 256 | 64 | 256 | 256 | 0.125 | 2 | 2 |
| E. coli PER-7 | ESBL | A | >2,048 | >2,048 | >2,048 | 16 | 256 | 256 | 1,024 | >2,048 | >2,048 | 16 | 256 | 256 | 64 | 256 | 256 | 0.125 | 2 | 2 |
| E. coli KPC-2 | Carba | A | 16 | 64 | 64 | 0.125 | 1 | 1 | 32 | 1024 | 1024 | ≤0.06 | 1 | 1 | 4 | 64 | 64 | ≤0.06 | 0.5 | 0.5 |
| E. coli KPC-3 | Carba | A | 32 | 256 | 256 | 0.125 | 2 | 2 | 64 | 2,048 | 2,048 | ≤0.06 | 1 | 1 | 4 | 256 | 256 | ≤0.06 | 0.5 | 0.5 |
| E. coli KPC-41 | Carba | A | 128 | 256 | 256 | 16 | 64 | 64 | 16 | 1,024 | 1,024 | ≤0.06 | 1 | 1 | 4 | 64 | 64 | 0.125 | 1 | 1 |
| E. coli KPC-46 | Carba | A | 64 | 256 | 256 | 0.25 | 4 | 4 | 128 | 2,048 | 2,048 | ≤0.06 | 1 | 1 | 8 | 256 | 256 | ≤0.06 | 0.5 | 0.5 |
| E. coli KPC-50 | Carba | A | 64 | 512 | 512 | 16 | 128 | 128 | 16 | 256 | 256 | ≤0.06 | 1 | 1 | 4 | 64 | 64 | 0.125 | 1 | 1 |
| E. coli IMI-1 | Carba | A | 1 | 4 | 4 | 0.25 | 1 | 1 | 128 | 2,048 | 2,048 | 0.5 | 4 | 4 | 0.125 | 2 | 2 | ≤0.06 | 0.25 | 0.25 |
| E. coli VIM-1 | Carba | B | 128 | 2,048 | 2,048 | 128 | >1,024 | >1,024 | ≤0.06 | 1 | 1 | ≤0.06 | 1 | 1 | 8 | 64 | 64 | 0.25 | 4 | 4 |
| E. coli VIM-2 | Carba | B | 32 | 256 | 256 | 32 | 256 | 256 | ≤0.06 | 1 | 1 | ≤0.06 | 1 | 1 | 0.125 | 1 | 1 | ≤0.06 | 0.25 | 0.25 |
| E. coli VIM-53 | Carba | B | 4 | 32 | 32 | 4 | 32 | 32 | ≤0.06 | 1 | 1 | ≤0.06 | 1 | 1 | 0.125 | 1 | 1 | ≤0.06 | 0.25 | 0.25 |
| E. coli VIM-83 | Carba | B | 512 | >2,048 | >2,048 | 512 | >1,024 | >1,024 | ≤0.06 | 1 | 1 | ≤0.06 | 1 | 1 | 16 | 512 | 512 | 16 | 512 | 512 |
| E. coli NDM-1 | Carba | B | 1,024 | >2,048 | >2,048 | 1,024 | >1,024 | >1,024 | ≤0.06 | 1 | 1 | ≤0.06 | 1 | 1 | 4 | 64 | 64 | 0.125 | 4 | 4 |
| E. coli NDM-5 | Carba | B | 1,024 | >2,048 | >2,048 | 1,024 | >1,024 | >1,024 | ≤0.06 | 1 | 1 | ≤0.06 | 1 | 1 | 2 | 64 | 64 | 0.125 | 4 | 4 |
| E. coli NDM-9 | Carba | B | 1,024 | >2,048 | >2,048 | 1,024 | >1,024 | >1,024 | ≤0.06 | 1 | 1 | ≤0.06 | 1 | 1 | 8 | 64 | 64 | 8 | 64 | 64 |
| E. coli IMP-1 | Carba | B | 512 | >2,048 | >2,048 | 512 | >1,024 | >1,024 | ≤0.06 | 1 | 1 | ≤0.06 | 1 | 1 | 8 | 128 | 128 | 8 | 128 | 128 |
| E. coli CMY-2 | Case | C | 64 | 512 | 512 | 0.5 | 2 | 2 | 32 | 256 | 256 | 0.5 | 4 | 4 | 0.5 | 16 | 8 | ≤0.06 | 0.25 | 0.25 |
| E. coli CMY-42 | Case | C | 128 | 512 | 512 | 1 | 4 | 4 | 64 | 256 | 256 | 1 | 8 | 8 | 2 | 8 | 8 | ≤0.06 | 0.25 | 0.25 |
| E. coli OXA-1 | Narrow | D | 0.125 | 0.5 | 1 | 0.125 | 0.5 | 1 | ≤0.06 | 1 | 1 | ≤0.06 | 1 | 1 | 0.5 | 16 | 16 | 0.125 | 2 | 2 |
| E. coli OXA-23 | Carba | D | 0.125 | 0.5 | 1 | 0.125 | 0.5 | 1 | ≤0.06 | 1 | 1 | ≤0.06 | 1 | 1 | ≤0.06 | 2 | 2 | ≤0.06 | 2 | 2 |
| E. coli OXA-48 | Carba | D | 0.125 | 0.5 | 0.5 | 0.125 | 0.5 | 1 | ≤0.06 | 1 | 1 | ≤0.06 | 1 | 1 | ≤0.06 | 1 | 1 | ≤0.06 | 0.25 | 0.25 |
| E. coli OXA-181 | Carba | D | 0.125 | 0.5 | 1 | 0.125 | 0.5 | 1 | ≤0.06 | 1 | 1 | ≤0.06 | 1 | 1 | ≤0.06 | 1 | 1 | ≤0.06 | 0.25 | 0.25 |
| E. coli OXA-427 | Carba | D | 32 | 128 | 128 | 1 | 8 | 8 | 1 | 32 | 32 | 0.25 | 2 | 2 | ≤0.06 | 2 | 2 | ≤0.06 | 0.25 | 0.25 |
a
WT: E. coli MG1655 wild type; YRIN: E. coli MG1655 with an amino-acid insertion (Tyr-Arg-Ile-Asn) in the PBP3 sequence; and YRIK: E. coli MG1655 with an amino-acid insertion (Tyr-Arg-Ile-Lys) in the PBP3 sequence. Narrow, narrow-spectrum; Case, cephalosporinase; ESBL, extended-spectrum β-lactamase; and Carba, carbapenemase.
b
MIC values shown in bold are those corresponding to at least a 64-fold change from the wild-type E. coli MG1655 MIC value of the corresponding antibiotic tested.
c
Shaded MIC values are those corresponding to a significantly elevated MIC value compared to wild-type E. coli MG1655, defined as an MIC value higher than eightfold compared to wild-type E. coli MG1655.