TABLE 2.

Overall performance of functional reporter strains

Type	Class	Gene	Reference compounda	Maximal induction (min)		Induction factorb (fold)		RLUc		Concn (μg/ml)		Z′d
				Arraye	Reporter	Array	Reporter	Basal	Induced	MIC	Inductionf
Generic pathways	Fatty acid biosynthesis	fabHB	Cerulenin	All	200	28.3	3.7	419	1,628	8	1-64	0.36
		glpDg	Cerulenin	All	180	12.6	2.0	74	218	8	1-8	<0
	Protein biosynthesis	yrzIh	Clindamycin	80	360	104.1	2.5	195	610	2	0.25-8	<0
	Cell wall biosynthesis	ypbGi	Vancomycin	40, 80	80	11.4	2.0	216	882	0.25	0.125-0.25	<0
Compound classes	Quinolonesj	dinBk	Ciprofloxacin	80	240	14.8	15.4	1,272	16,928	0.5	0.06-4	0.43
		yneAl	Ciprofloxacin	80	240	19.0	16.1	218	4,487	0.5	0.125-4	0.54
		yorBl	Ciprofloxacin	80	200	14.1	28.1	616	18,181	0.5	0.06-4	0.51
	Glycopeptides	ytrA	Vancomycin	10	40	42.9	3.4	228	1,550	0.25	0.125-2	0.26
		ywoB	Vancomycin	10	60	62.1	1.9	45	101	0.25	0.125-2	<0
Individual compounds	Cycloserine	ydeK	Cycloserine	40	160	56.2	2.2	92	382	32	8-64	0.02
	Rifampicin	yvgS	Rifampicin	80	80	46.2	3.7	86	322	0.125	0.008-0.125	<0
	Clindamycin	expZ	Clindamycin	All	300	76.3	5.1	116	644	2	0.25-2	0.03

^aCompound for which the highest level of upregulation was observed in expression profiling experiments. This compound was also used to determine Z′.

^bInduction factors for the reporter strains were calculated from a set of experiments designed to evaluate the reporter strains in a high-throughput mode.

^cRLU, mean relative light units, as measured in a set of experiments designed to evaluate the functionality of the reporter strains (see Results). Indicated are the values measured without compound treatment (basal) and after treatment with the reference compounds (induced) at the optimal time points and concentrations.

^dThe Z′ factor is a measure of assay robustness in high-throughput applications (35).

^eGene expression profiles were collected after 10, 40, and 80 min of compound treatment.

^fConcentration window in which significant upregulation was observed.

^gglpD was selected as a specific marker gene for triclosan, but the reporter strain was responsive to cerulenin as well.

^hTwo false-negative (puromycin and actinonin) and three compounds that elicited unexpected positive responses (5-fluoruracil, nitrofurantoin, and nalidixic acid) were detected with the yrzI reporter strain.

ⁱOne false-negative (ristocetin) and one compound that elicited an unexpected positive response (polymyxin B) were detected with the ypbG reporter strain.

^jGenes were selected as marker genes for topoisomerases, but not all strains elicited a signal with the coumarins.

^kTwo compounds that elicited unexpected positive responses were detected with the dinB reporter strain, azaserine and 5 fluoruracil.

^lOne compound that elicited an unexpected positive response was detected with the yneA and the yorB reporter strains, azaserine.