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. 2017 Nov 21;8:2278. doi: 10.3389/fmicb.2017.02278

Table 2.

Mutations of the MCR-1, MgrB, PhoP, PhoQ, PmrA, and PmrB amino-acid sequences observed only in the 79 colistin-resistant (CSTR) or the 2 mcr-1-positive colistin-susceptible (CSTS) isolates.

Target (number of full sequences obtained) Amino acid mutations (number of CSTR or mcr-1-positive CSTS isolates) GPR in which the gene or mutation is present (see Table 4) Previously described similar mutations
MCR-1 (72 isolates) GPR 1, 2, 4, 6–11, 14, 15, 17, 18
MgrB (79 CSTR, 2 mcr-1-positive CSTS and 9 mcr-1-negative CSTS isolates&) V8A (1 CSTR)
Q33R (3 CSTR)
GPR 3
GPR 4
L8Y in CSTR K. pneumoniae* (Olaitan et al., 2014a)
D31N in CSTR K. pneumoniae *(Olaitan et al., 2014a)
PhoP (79 CSTR, 2 mcr-1-positive CSTS and 9 mcr-1-negative CSTS isolates&) V108M (28 CSTR)
A182P (1 CSTR)
GPR 2
GPR 5
V108M frequent in GenBank, impact on CSTR unknown
PhoQ (79 CSTR, 2 mcr-1-positive CSTS and 9 mcr-1-negative CSTS isolates&) L87P (1 CSTR)
S138T (8 CSTR)
A166V (1 CSTR)
I175F (3 CSTR)
E464D (29 CSTR and 1 mcr-1-positive CSTS isolates) A482T (29 CSTR and 1 mcr-1-positive CSTS isolates)
GPR 6
GPR 4, 8
GPR 9
GPR 10
GPR 2, 11
GPR 2, 11
Many detected mutations in E. coli, impact on CSTR unknown (Anjum et al., 2016)
L96P, S174N, L348Q and G385S in CSTR K. pneumoniae *(Olaitan et al., 2014b)
PmrA (78 CSTR, 2 mcr-1-positive CSTS and 9 mcr-1-negative CSTS isolates&)
PmrB (79 CSTR, 2 mcr-1-positive CSTS and 9 mcr-1-negative CSTS isolates&) E123D (1 CSTR)
S138N (9 CSTR)
T156A (1 CSTR)
G160E (1 CSTR)
V161G (5 CSTR)
V351I (2 CSTR)
A361V (1 mcr-1-positive CSTS isolate) Truncated protein: 5 amino acids (1 CSTR) or 149 amino acids (1 CSTR)
GPR 3
GPR 4, 7, 8
GPR 2
GPR 12
GPR 13, 14
GPR 3, 7
GPR 15
GPR 16, 17
E121A, S124P in CSTR Salmonella, impact on CSTR unknown (Anjum et al., 2016)
T140P, T157P in K. pneumoniae* (Olaitan et al., 2014b)
V161L/M/G in Salmonella (Anjum et al., 2016) and V161G in E. coli (Quesada et al., 2015), impact on CSTR unknown

GPR, Genetic profiles of resistance, see Table 4 which gives for each GPR the different modifications observed in the sequenced genes (the impact of the mutations detected in this study has not been demonstrated).

*

Shown to contribute to CST-resistance.

&

The genes encoding MgrB, PhoP, PhoQ, PmrA and PmrB were sequenced for all isolates, and the results obtained for the 79 CSTR isolates and the two mcr-1-positive CSTS isolates were compared to those obtained for the nine mcr-1-negative CSTS isolates which had inhibition zone diameter higher than 17 mm (Table S1).