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)S42N120
G53C105, 120
G53S105
Trans_reg_C (145–216)
PmrB (365)TM (13–35)ΔR14118
L17Q105
HAMP (90–142)L82R116
S85R120
T140P120
HisKA (143–203)T157P117119
S208N118
ΔY209118
HATPase_c (250–358)R256G117
PhoP (223)REC (1–112)V3F117
L26Q120
S86L117
Trans_reg_C (145–220)D191Y81
PhoQ (488)PhoQ sensor (10–189)R16C105
L26P117
L96P120
D150G117
S174N118
HAMP (195–263)V258F117
HisKA (267–330)
L348Q120
HATPase_c (375–482)G385S120
D434N128
MgrB (47)K3*105
L9*120
I13*120
A14S120
W20R105
L24H130
V26*120
M27K105
C28F120
C28Y117, 120, 128, 130
C28*105, 120
Q30*105, 120
D31N120
Q33*105
F35I120
G37S130
C39Y105
N42Y/K43I105
I45T105
W47R105
W47*105
*48Y117
CrrB (353)Q10L128, 137
TM (12–34)Y31H137
HAMP (81–135)L94 M128
HisKA (136–200)W140R137
N141I137
P151S137
S195N137
    E. aerogenesPmrAG53S121
    E. coliPmrA (222)REC (1–112)R81Sc125
Trans_reg_C (145–216)
PmrB (363)Δ7–12c124
TM1 (15–37)
TM2 (69–91)
HAMP (92–144)
HisKA (145–205)T156Kc124
A159Vc124
V161Gc125
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)E375Kc65
    S. entericaPmrA (222)REC (1–112)G15Rc123
G53Ec123
G53Rc123
R81Cc123
R81Hc123
Trans_reg_C (145–216)
PmrB (356)TM (13–35)Δ11–14c122
L14Fc123
L14Sc123
M15Lc122
L22Pc123
S29Rc123
HAMP (89–141)T92Ac123
P94Qc123
E121Ac123
S124Pc123
N130Yc123
HisKA (142–202)T147Pc123
R155Pc123
T156Mc123
T156Pc123
V161Gc123
V161Lc123
V161Mc123
E166Kc123
M186Ic123
HATPase_c (249–356)G206Rc123
G206Wc123
S305Rc123
Nonfermentative bacilli
    P. aeruginosaPmrA (221)REC (1–112)
Trans_reg_C (145–216)L157Q166
PmrB (477)L14P167
TM1 (15–37)
PD (38–160)ΔD4574, 167
A54V167
TM2 (161–183)L167P166
HAMP (186–238)G188D167
F237L118
HisKA (239–304)L243Q167
A247T168
A248V167
S257N167
M292I167
M292T169
HATPase_c (348–459)
PhoQ (448)R6C170
TM1 (7–29)
ΔV57–Q332170
PD (30–166)N104I118
K123Q166
K123E118
Q133E118
A143V166
V152*168
TM2 (167–189)V184G118
A207R118
R214H118
H223R168
HisKA (238–300)V260G163, 247
HATPase_c (343–448)ΔL364–G365170
I421*170
Fr at I421170
D433*170
R444C170
ParR (235)REC (7–117)L18I118
N24S118
S24N118
M59I171
Trans_reg_C (152–228)E156K171
ParS (428)TM1 (5–27)L14Q171
PD (28–131)V101 M171
TM2 (132–154)L137P171
HAMP (155–207)
HisKA (208–273)Q232E118
HATPase_c (318–428)G361R118
H398R247
ColSA106V172
CprSR241C172
    A. baumanniiPmrA (224)REC (2–112)E8D177, 180
M12I174
P102H173
S119T174
Trans_reg_C (150–221)
PmrB (444)TM1 (10–29)T13N173
S14L175
S17R177
Fr at F26176
PD (30–141)ΔA32–E35174
D64V174
A80V174
L87F175
Y116H177
I121F178
TM2 (142–164)M145K175
ΔL160174
P170L174, 179
P170Q174
A183T178
A184V178
P190S178
T192I178
L208F174
HisKA (218–280)A226V174
A227V173, 175, 176
Q228P178
R231L174
T232I177
P233S118, 173176, 179
P233T173
T235I174
N256I174
A262P173
R263C174
R263L177
R263P174
Q277H174
G315D174
HATPase_c (326–437)N353Y175
P377L174
F387Y175
S403F175
LpxA (262)Fr at I25109
G68D109
Q72K109
Fr at H121109
Fr at D130109
H159D109
Q234*109
LpxC (276)P30L109
Fr at D45109
Fr at T285109
LpxD (356)Fr at K317109
  • 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.