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 speciesProtein (normal length [aa])Domain involved (residues)a,bAmino acid changedReference(s)
Enterobacteriaceae
    K. pneumoniaePmrA (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. aerogenesPmrA G53S 121
    E. coliPmrA (222)REC (1–112)R81Sc 125
Trans_reg_C (145–216)
PmrB (363) Δ7–12c 124
TM1 (15–37)
TM2 (69–91)
HAMP (92–144)
HisKA (145–205)T156Kc 124
A159Vc 124
V161Gc 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)E375Kc 65
    S. entericaPmrA (222)REC (1–112)G15Rc 123
G53Ec 123
G53Rc 123
R81Cc 123
R81Hc 123
Trans_reg_C (145–216)
PmrB (356)TM (13–35)Δ11–14c 122
L14Fc 123
L14Sc 123
M15Lc 122
L22Pc 123
S29Rc 123
HAMP (89–141)T92Ac 123
P94Qc 123
E121Ac 123
S124Pc 123
N130Yc 123
HisKA (142–202)T147Pc 123
R155Pc 123
T156Mc 123
T156Pc 123
V161Gc 123
V161Lc 123
V161Mc 123
E166Kc 123
M186Ic 123
HATPase_c (249–356)G206Rc 123
G206Wc 123
S305Rc 123
Nonfermentative bacilli
    P. aeruginosaPmrA (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. baumanniiPmrA (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, 173176, 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
  • a 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.

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

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

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