TABLE 1.

EPI efficacies detected with mutants derived from serial selection with drug/EPI compared to reference strains

Strain	EPI efficacy witha:
	LVX		CHL		OXA		LZD		MIN		NOV		CLR		RIF
	NMP	PAβN	NMP	PAβN	NMP	PAβN	NMP	PAβN	NMP	PAβN	NMP	PAβN	NMP	PAβN	NMP	PAβN
Reference strains
AG100	2	2 (0.06)	2	2 (2)	4	4 (128)	16	8 (256)	8	4 (1)	4	32 (64)	4	64 (128)	2	64 (8)
3-AG100	8	8 (2)	8	8 (16)	8	8 (512)	32	8 (1,024)	8	16 (4)	8	128 (1,024)	2	32 (256)	4	64 (16)
ΔAcrBb	1	1 (0.06)	2	1 (1)	1	1 (0.5)	1	2 (16)	4	4 (0.25)	8	8 (4)	2	8 (4)	2	128 (8)
Mutantsc
4B/15	4	8 (2)	4	8 (32)	2	4 (128)	8	32 (>2,048)	2	8 (4)	4	16 (1,024)	1	64 (128)	2	128 (16)
C5/1/17	4	1 (0.25)	4	2 (4)	1	2 (128)	16	4 (512)	2	2 (1)	4	16 (128)	1	2 (2,048)	1	8 (2)

^aThe relative EPI efficacy was defined as the ratio of the MICs in the absence and in the presence of the EPI (NMP or PAβN, respectively). MICs in µg/ml (without EPI) are given in parentheses; EPI efficacies and mutant MIC changes of ≥4-fold compared to values for the parental AcrB-overexpressing strain 3-AG100 are in bold. LVX, levofloxacin; CHL, chloramphenicol, OXA, oxacillin, LZD, linezolid, MIN, minocycline, NOV, novobiocin, CLR, clarithromycin; RIF, rifampin. Gentamicin was used in addition as a control drug (no AcrB substrate), showing no changes in relative NMP efficacy and MIC (data not shown) similar to rifampin (poor AcrB substrate).

^bAcrB knockout derived from the AcrB-overexpressing E. coli strain 3-AG100 (AG100 is the wild-type control strain).

^cStrain 4B/15 was from serial selection experiments with LZD/NMP (second-step mutant); C5/1/17 was selected with CLR/PAβN (third-step mutant).