TABLE 1 .

Chromosomal resistance mutations

Gene	Gene functiona	Mutant allele	Fitness cost (%)a,b	Resistance to the followinga:	Resistance mechanism	Reference(s)
gyrAc	Gyrase	S83F	BDL	CIP	Target alteration	51
rpoBc	RNA PM	S531L	23	RIF	Target alteration	52
rpsLc	Ribosomal protein	K42N	22	STM	Target alteration	53
fusAc	EF-G	P413L	52	FUS	Target alteration	54
fmtc	Formyltransferase	T12R	67	ACT	Target bypass	55
gidB	Methyltransferase	Q167*	BDL	STM	Target alteration	56
ompRd	TF	Δ	BDL	MDR	Influx/efflux	57, 58
marRd	TF	Q110*	BDL	MDR	Influx/efflux	59
lond	Protease	Q137*	43	MDR	Influx/efflux	60, 61
mgrBd	Autoregulator	Δ	BDL	Col	Influx/efflux	62
pmrA	TF	G53E	BDL	Col	Influx/efflux	63
acrR	TF	H115Y	BDL	MDR	Influx/efflux	64
cysB	TF	Δ	26	MEC	Unknown	65

^aAbbreviations: BDL, below detection limit (<3%); PM, polymerase; EF, elongation factor; TF, transcription factor; CIP, ciprofloxacin; RIF, rifampin; STM, streptomycin; FUS, fusidic acid; ACT, actinonin; Col, colistin; MEC, amdinocillin; MDR, multidrug resistance.

^bThe value represents the fitness cost of the mutation in S. Typhimurium LT2, expressed as the relative exponential growth rate compared to the growth rate of the wild type.

^cThese mutations were used to construct combinatorial sets of target alteration mutations.

^dThese mutations were used to construct combinatorial sets of regulator mutations.