TABLE 3.
Characterization and susceptibilities of mutants generated from in vitro spontaneous resistance studies for SMC-3176 in P. aeruginosa
| Parent/mutant (selection concn [×MIC]) | Mutationa | MIC in MHB (mg/liter) |
|||||
|---|---|---|---|---|---|---|---|
| SMC-3176 | MB-1 | MC-8 | Aztreonam | Ceftazidime | Meropenem | ||
| PAO1 | 0.25 | 0.5 | 0.5 | 4 | 2 | 1 | |
| A1-PAO1 (4) | Δ[PiuC(PA4515)…PA4521]b | 4 | 4 | 16 | 4 | 1 | 2 |
| A2-PAO1 (8) | pfecI (−44 T→C)c | 32 | 8 | 16 | 8 | 2 | 2 |
| ARC3483 | 0.25 | 0.5 | 0.5 | 2 | 1 | 0.5 | |
| B1-ARC3483 (2) | PiuC [Q177fs] | 8 | 16 | 16 | 2 | 0.5 | 0.5 |
| ARC3502 | 0.25 | 0.25 | 0.25 | 64 | >64 | >64 | |
| C1-ARC3502 (4) | PiuA [Q186fs] | 8 | 4 | 4 | 32 | >64 | >64 |
| C2-ARC3502 (4) | pfecI (−41 C→A)c | 4 | 4 | 8 | 32 | >64 | >64 |
| C3-ARC3502 (8) | PiuA [Q604fs] | 8 | 8 | 4 | >64 | >64 | >64 |
| ARC3506 | 0.25 | 1 | 0.25 | >64 | >64 | 4 | |
| D2-ARC3506 (8) | pfecI (−45 C→T)c | 32 | 32 | 32 | >64 | >64 | 16 |
| ARC3514 | 0.13 | 0.13 | 0.13 | >64 | >64 | >64 | |
| E1-ARC3514 (4) | PiuC [W175*] | 1 | 8 | 2 | >64 | >64 | >64 |
| E2-ARC3514 (8) | ppvdS (−88 T→A)c | 2 | >64 | 8 | >64 | >64 | >64 |
| E3-ARC3514 (16) | PirR [G132fs] | 1 | 2 | 1 | >64 | >64 | >64 |
a
Mutations noted by amino acid changes in coding regions or base pair changes in gene promoter. fs, frameshift; p, promoter.
b
Indicates a 8,725-bp deletion (5056096..5064820 relative to PAO1) encompassing PiuC (PA4515) through PA4521 and the terminal 14 amino acids of AmpD [W174fs].
c
Point mutation in promoter at predicted Fur binding site.