TABLE 3.

Cross-resistance, increased β-lactamase activity, and expression of efflux pumps in resistant colonies^a

Antibiotic used for selectionb and strain	MIC (μg/ml)c					Fold changed in:
						β-Lactamase activitye		Efflux pump expression
	CAZ	CIP	TOB	CHL	TET	Basal	Induced	mexF	mexD	mexB	mexY
None, PAO1	2	0.19	1.5	32	4
CAZ
PAO1	20	0.125	1.75	ND	ND	4.4	1.07	ND	ND	ND	ND
mutT mutant	18	0.17	2	ND	ND	5.6	0.78	ND	ND	ND	ND
mutY mutant	26	0.13	2	ND	ND	4.9	0.88	ND	ND	ND	ND
mutM mutant	18	0.16	2	ND	ND	5.4	0.87	ND	ND	ND	ND
TOB
PAO1	0.5	0.32	6	28 (+)	10	ND	ND	1.18	1.88	1.29	2.4
mutT mutant	0.69	0.16	3.75	86 (+)	5.5	ND	ND	1.04	0.86	0.89	0.76
mutY mutant	0.63	0.11	3.5	56 (+)	18	ND	ND	2.05	1.57	0.94	2
mutM mutant	0.38	0.08	0.9	20 (+)	4.25	ND	ND	ND	ND	ND	ND
CIP
PAO1	0.44	0.75	1.06	>256	>256	ND	ND	1.25	618.73	5.5	1.77
mutT mutant	0.47	0.75	1.37	>256	>256	ND	ND	0.97	607.77	1.07	1.04
mutY mutant	0.44	0.88	1.19	>256	>256	ND	ND	0.75	437.72	0.59	0.89
mutM mutant	0.44	0.75	1.25	>256	>256	ND	ND	11.3	342.16	0.73	5.7

^aFrom the population analysis of the GO gene (mutT, mutY, and mutM) mutants isolated after selection on ceftazidime, tobramycin, or ciprofloxacin.

^bCAZ, ceftazidime; TOB, tobramycin; CIP, ciprofloxacin.

^cEach MIC is the mean for four colonies (two successive determinations per colony), except for PAO1 after selection on tobramycin, where the MIC is the mean for two colonies. CHL, chloramphenicol; TET, tetracycline; ND, not detected. Plus signs in parentheses indicate that the colonies isolated from LB agar plates containing tobramycin showed a small subpopulation resistant to chloramphenicol.

^dRelative to the respective nonresistant strain.

^eThe induced β-lactamase activity of PAO1 was 26.5-fold higher than its basal β-lactamase activity.