. 2017 Mar 8;30(2):557–596. doi: 10.1128/CMR.00064-16

TABLE 3.

Chromosomal mutations and amino acid deletions responsible for acquired colistin resistance in Klebsiella pneumoniae, Enterobacter aerogenes, Escherichia coli, Salmonella enterica, P. aeruginosa, and A. baumannii isolates

Bacterial group and species	Protein (normal length [aa])	Domain involved (residues)^a^,^b	Amino acid change^d	Reference(s)
Enterobacteriaceae
K. pneumoniae	PmrA (223)	REC (1–112)	S42N	120
			G53C	105, 120
			G53S	105
		Trans_reg_C (145–216)
	PmrB (365)	TM (13–35)	ΔR14	118
			L17Q	105
		HAMP (90–142)	L82R	116
			S85R	120
			T140P	120
		HisKA (143–203)	T157P	117 –119
			S208N	118
			ΔY209	118
		HATPase_c (250–358)	R256G	117
	PhoP (223)	REC (1–112)	V3F	117
			L26Q	120
			S86L	117
		Trans_reg_C (145–220)	D191Y	81
	PhoQ (488)	PhoQ sensor (10–189)	R16C	105
			L26P	117
			L96P	120
			D150G	117
			S174N	118
		HAMP (195–263)	V258F	117
		HisKA (267–330)
			L348Q	120
		HATPase_c (375–482)	G385S	120
			D434N	128
	MgrB (47)		K3*	105
			L9*	120
			I13*	120
			A14S	120
			W20R	105
			L24H	130
			V26*	120
			M27K	105
			C28F	120
			C28Y	117, 120, 128, 130
			C28*	105, 120
			Q30*	105, 120
			D31N	120
			Q33*	105
			F35I	120
			G37S	130
			C39Y	105
			N42Y/K43I	105
			I45T	105
			W47R	105
			W47*	105
			*48Y	117
	CrrB (353)		Q10L	128, 137
		TM (12–34)	Y31H	137
		HAMP (81–135)	L94 M	128
		HisKA (136–200)	W140R	137
			N141I	137
			P151S	137
			S195N	137
E. aerogenes	PmrA		G53S	121
E. coli	PmrA (222)	REC (1–112)	R81S^c	125
		Trans_reg_C (145–216)
	PmrB (363)		Δ7–12^c	124
		TM1 (15–37)
		TM2 (69–91)
		HAMP (92–144)
		HisKA (145–205)	T156K^c	124
			A159V^c	124
			V161G^c	125
		HATPase_c (252–360)
		PhoQ_sensor (10–189)
		HAMP (195–263)
		HisKA (267–330)
	PhoP (223)	REC (1–112)
		Trans_reg_C (145–220)
	PhoQ (486)	PhoQ_sensor (10–189)
		HAMP (195–263)
		HisKA (267–330)
		HATPase_c (374–480)	E375K^c	65
S. enterica	PmrA (222)	REC (1–112)	G15R^c	123
			G53E^c	123
			G53R^c	123
			R81C^c	123
			R81H^c	123
		Trans_reg_C (145–216)
	PmrB (356)	TM (13–35)	Δ11–14^c	122
			L14F^c	123
			L14S^c	123
			M15L^c	122
			L22P^c	123
			S29R^c	123
		HAMP (89–141)	T92A^c	123
			P94Q^c	123
			E121A^c	123
			S124P^c	123
			N130Y^c	123
		HisKA (142–202)	T147P^c	123
			R155P^c	123
			T156M^c	123
			T156P^c	123
			V161G^c	123
			V161L^c	123
			V161M^c	123
			E166K^c	123
			M186I^c	123
		HATPase_c (249–356)	G206R^c	123
			G206W^c	123
			S305R^c	123
Nonfermentative bacilli
P. aeruginosa	PmrA (221)	REC (1–112)
		Trans_reg_C (145–216)	L157Q	166
	PmrB (477)		L14P	167
		TM1 (15–37)
		PD (38–160)	ΔD45	74, 167
			A54V	167
		TM2 (161–183)	L167P	166
		HAMP (186–238)	G188D	167
			F237L	118
		HisKA (239–304)	L243Q	167
			A247T	168
			A248V	167
			S257N	167
			M292I	167
			M292T	169
		HATPase_c (348–459)
	PhoQ (448)		R6C	170
		TM1 (7–29)
			ΔV57–Q332	170
		PD (30–166)	N104I	118
			K123Q	166
			K123E	118
			Q133E	118
			A143V	166
			V152*	168
		TM2 (167–189)	V184G	118
			A207R	118
			R214H	118
			H223R	168
		HisKA (238–300)	V260G	163, 247
		HATPase_c (343–448)	ΔL364–G365	170
			I421*	170
			Fr at I421	170
			D433*	170
			R444C	170
	ParR (235)	REC (7–117)	L18I	118
			N24S	118
			S24N	118
			M59I	171
		Trans_reg_C (152–228)	E156K	171
	ParS (428)	TM1 (5–27)	L14Q	171
		PD (28–131)	V101 M	171
		TM2 (132–154)	L137P	171
		HAMP (155–207)
		HisKA (208–273)	Q232E	118
		HATPase_c (318–428)	G361R	118
			H398R	247
	ColS		A106V	172
	CprS		R241C	172
A. baumannii	PmrA (224)	REC (2–112)	E8D	177, 180
			M12I	174
			P102H	173
			S119T	174
		Trans_reg_C (150–221)
	PmrB (444)	TM1 (10–29)	T13N	173
			S14L	175
			S17R	177
			Fr at F26	176
		PD (30–141)	ΔA32–E35	174
			D64V	174
			A80V	174
			L87F	175
			Y116H	177
			I121F	178
		TM2 (142–164)	M145K	175
			ΔL160	174
			P170L	174, 179
			P170Q	174
			A183T	178
			A184V	178
			P190S	178
			T192I	178
			L208F	174
		HisKA (218–280)	A226V	174
			A227V	173, 175, 176
			Q228P	178
			R231L	174
			T232I	177
			P233S	118, 173 –176, 179
			P233T	173
			T235I	174
			N256I	174
			A262P	173
			R263C	174
			R263L	177
			R263P	174
			Q277H	174
			G315D	174
		HATPase_c (326–437)	N353Y	175
			P377L	174
			F387Y	175
			S403F	175
	LpxA (262)		Fr at I25	109
			G68D	109
			Q72K	109
			Fr at H121	109
			Fr at D130	109
			H159D	109
			Q234*	109
	LpxC (276)		P30L	109
			Fr at D45	109
			Fr at T285	109
	LpxD (356)		Fr at K317	109

Domains predicted in SMART by using protein sequences of Escherichia coli K-12 substrain MG1655, Klebsiella pneumoniae subsp. pneumoniae MGH 78578, Salmonella enterica serovar Typhimurium LT2, P. aeruginosa PAO1, and A. baumannii AB0057. REC, CheY-homologous receiver domain; Trans_reg_C, transcriptional regulatory protein, C-terminal domain; TM, transmembrane domain; TM1, first transmembrane domain; TM2, second transmembrane domain; PD, periplasmic domain; HAMP, histidine kinases, adenylyl cyclases, methyl-binding proteins, and phosphatases; HisKA, histidine kinase A (phosphoacceptor) domain; HATPase_c, histidine kinase-like ATPases; PhoQ sensor, phosphorelay signal transduction system.

A periplasmic domain (PD) was not predicted in SMART but was assumed to be between TM1 and TM2.

The involvement of the mutation in the colistin resistance profile was determined by in silico analysis.

Δ, deletion; Fr, frameshift; *, stop codon.