TABLE 3.

Effects of efflux and porins on activity of beta-lactam antibiotics against a panel of isogenic strains of Klebsiella pneumoniae with efflux and porin mutations^a

Strain	Genotype	AcrAB-TolC	OmpK35	OmpK36	MIC (μg/mL)
					Tebipenem	Ceftibuten	Cefixime	Cefpodoxime	Cefdinir	Cefditoren	Cefaclor	Mecillinam	Cefuroxime	Cephalexin
KPM1026Ab	WT	WT	WT	WT	≤0.06	0.125	0.125	0.125	0.125	0.5	0.5	0.5	2	4
PAM2696	ΔacrAB	None	WT	WT	≤0.06	≤0.06	≤0.06	≤0.06	≤0.06	≤0.06	1	≤0.06	0.125	4
KPM1027c	ramR f	Up	Down	WT	≤0.06	0.25	0.5	2	1	2	1	2	32	8
KPM2600	ΔompK35	WT	NF	WT	≤0.06	0.125	0.125	0.25	0.125	0.25	0.5	0.5	4	4
KPM2610	ramRf ΔompK35	Up	NF	WT	≤0.06	0.25	0.5	2	2	2	1	2	16	8
KPM2592	ΔompK36	WT	WT	NF	0.125	0.25	0.25	0.5	1	0.5	2	>64	8	16
KPM2040d	ompK36_2067	WT	WT	NF	0.125	0.25	0.25	0.5	2	1	2	16	16	16
KPM2613	ompK36_2067 ΔompK35	WT	NF	NF	0.5	0.25	0.5	1	2	1	4	>64	16	32
KPM2126	ramRe ompK36_2013	Up	Down	NF	1	1	2	4	8	4	16	>64	64	>64
KPM2658	ramRf ΔompK36	Up	Down	NF	2	1	1	4	8	4	16	>64	32	>64

^aAll strains contain chromosomal SHV enzyme, encoded by bla_SHV-24. WT, wild type; NF, nonfunctional; Up, upregulated; Down, downregulated.

^bKPM1026a is a streptomycin-resistant mutant of the wild-type strain KPM1001 (ATCC 43816). It contains a functional acrAB operon and functional genes ompK35 and ompK36.

^cKPM1027 is a derivative of KPM1026a selected on tigecycline. It has an inactivating mutation in the negative regulator gene ramR (frameshift from amino acid 46 in the RamR protein) and as a result has the acrAB operon overexpressed ∼3-fold and the ompK35 gene downregulated ∼10-fold relative to KPM1026a. Expression of ompK36 in KPM1027 is unchanged relative to KPM1026a.

^dInsertion of base A at nucleotide 160 of ompK36, causing a frameshift from amino acid 54 of OmpK36.

^eC364T substitution in ramR created TAG at amino acid 122, resulting in overexpression of acrAB and downregulation of ompK35.

^fInsertion of 8 bp in ramR causing a frameshift from amino acid 46, resulting in overexpression of acrAB and downregulation of ompK35.