Susceptibility to β-lactams and expression of <i>ampC</i> and <i>creD</i> genes in the studied mutants.

aPAO1, wild-type reference strain; PAΔC, ampC knockout mutant of PAO1; PAΔR, ampR knockout mutant of PAO1; PAΔD, ampD knockout mutant of PAO1; PAΔE, ampE knockout mutant of PAO1; PAΔDE, ampD-ampE knockout mutant of PAO1; PAΔDDh2Dh3, ampD triple (ampD-ampDh2-ampDh3) knockout mutant of PAO1; PAΔDDh2Dh3R, ampR knockout mutant of PAΔDDh2Dh3; PAΔdacB, dacB knockout mutant of PAO1; 1A1 (DacB W273X), DacB W273X in vitro spontaneous mutant of PAO1; 1A1ΔC, ampC knockout mutant of 1A1; 1A1ΔR, ampR knockout mutant of 1A1; 1A1ΔD, ampD knockout mutant of 1A1; 1A1ΔE, ampE knockout mutant of 1A1;2A2 (DacB frameshift), in vivo spontaneous mutant of PAO1 containing a deletion of nts 1074–1078 in dacB; PAΔcreBC, creBC knockout mutant of PAO1; PAΔDDh2Dh3creBC, creBC knockout mutant of PAΔDDh2Dh3creBC; 1A1ΔcreBC, creBC knockout mutant of 1A1; 2A2ΔcreBC, creBC knockout mutant of 2A2; 1A1ΔcreD, creD knockout mutant of 1A1. bCAZ, ceftazidime; CEP, cefepime; PIP, piperacillin; PIP/TZ, piperacillin-tazobactam; ATM, aztreonam; IMP, imipenem. cClinical Laboratory Standards Institute (CLSI) susceptibility breakpoints: CAZ, CEP, and ATM≤8 µg/ml; PIP and PIP/TZ≤64 µg/ml; IMP≤4 µg/ml. dRelative amount of ampC or creD mRNA compared to PAO1 basal level±standard deviation. Induction experiments were carried out with 50 µg/ml cefoxitin. eNA, not applicable; ND, not determined.