TABLE 1.
PRR values for MCR protein-producing E. coli clones and colistin-resistant and colistin-susceptible clinical E. coli strains used in this studya
| Strain | Colistin MIC (mg/liter) | Resistance mechanism | Additional β-lactamase gene(s) | PRR | PRR1,919 | PRR1,927 |
|---|---|---|---|---|---|---|
| MCR protein-producing E. coli clones | ||||||
| MC1000 pDM1-mcr-1 | 4 | mcr-1 | 6.63 ± 0.68 | 6.63 ± 0.68 | 0.00 ± 0.00 | |
| MC1000 pDM1-mcr-2 | 4 | mcr-2 | 4.80 ± 0.72 | 4.80 ± 0.72 | 0.00 ± 0.00 | |
| MC1000 pDM1-mcr-3 | 4 | mcr-3 | 4.54 ± 0.15 | 4.54 ± 0.15 | 0.00 ± 0.00 | |
| MC1000 pDM1-mcr-4 | 4 | mcr-4 | 4.47 ± 0.78 | 4.47 ± 0.78 | 0.00 ± 0.00 | |
| MC1000 pDM1-mcr-5 | 4 | mcr-5 | 4.00 ± 1.29 | 4.00 ± 1.29 | 0.00 ± 0.00 | |
| MC1000 pDM1-mcr-8 | 4 | mcr-8 | 3.36 ± 1.44 | 3.36 ± 1.44 | 0.00 ± 0.00 | |
| MC1000 pDM1 | 0.5 | 0.00 ± 0.00 | 0.00 ± 0.00 | 0.00 ± 0.00 | ||
| Colistin-resistant strains harboring mcr genes | ||||||
| CNR 20140385 | 4 | mcr-1 | OXA-48 | 0.91 ± 0.18 | 0.91 ± 0.18 | 0.00 ± 0.00 |
| S08-056 | 4 | mcr-1 | OXA-48 | 1.86 ± 0.28 | 1.86 ± 0.28 | 0.00 ± 0.00 |
| CNR 117 G7 | 4 | mcr-1 | NDM-1 | 1.70 ± 0.68 | 1.70 ± 0.68 | 0.00 ± 0.00 |
| CNR 1745 | 4 | mcr-1 | SHV-12 | 1.65 ± 0.02 | 1.65 ± 0.02 | 0.00 ± 0.00 |
| CNR 1604 | 4 | mcr-1 | CTX-M-15 | 1.98 ± 0.30 | 1.98 ± 0.30 | 0.00 ± 0.00 |
| CNR 1790 | 4 | mcr-1 | TEM-15 | 1.37 ± 0.05 | 1.37 ± 0.05 | 0.00 ± 0.00 |
| CNR 1859 | 4 | mcr-1 | CTX-M-15, SHV-12, TEM-1 | 2.95 ± 0.10 | 2.95 ± 0.10 | 0.00 ± 0.00 |
| CNR 1886 | 4 | mcr-1 | CTX-M-1, TEM-1 | 1.05 ± 0.11 | 1.05 ± 0.11 | 0.00 ± 0.00 |
| 4222 | 4 | mcr-1 | CTX-M-2 | 1.75 ± 0.42 | 1.75 ± 0.42 | 0.00 ± 0.00 |
| 4070 | 4 | mcr-1 | TEM-1B | 0.98 ± 0.03 | 0.98 ± 0.03 | 0.00 ± 0.00 |
| 979 | 4 | mcr-1 | CTX-M-2 | 1.75 ± 0.26 | 1.75 ± 0.26 | 0.00 ± 0.00 |
| 1724 | 4 | mcr-1 | 1.28 ± 1.21 | 1.28 ± 1.21 | 0.00 ± 0.00 | |
| CNR 164 A5 | 4 | mcr-1 | 1.56 ± 0.44 | 1.56 ± 0.44 | 0.00 ± 0.00 | |
| 1670 | 4 | mcr-1.5 | CTX-M-2 | 1.21 ± 0.32 | 1.21 ± 0.32 | 0.00 ± 0.00 |
| 6383 | 4 | mcr-1.5 | TEM-1B | 1.75 ± 0.08 | 1.75 ± 0.08 | 0.00 ± 0.00 |
| R12 F5 | 4 | mcr-2 | 0.66 ± 0.08 | 0.66 ± 0.08 | 0.00 ± 0.00 | |
| 37922 | 4 | mcr-3.2 | CTX-M-55 | 1.52 ± 0.18 | 1.52 ± 0.18 | 0.00 ± 0.00 |
| 1144230 | 4 | mcr-5 | CMY-2 | 1.09 ± 0.20 | 1.09 ± 0.20 | 0.00 ± 0.00 |
| J53 pMCR-8 (Kpn) | 4 | mcr-8 | 0.25 ± 0.03 | 0.25 ± 0.03 | 0.00 ± 0.00 | |
| Colistin-resistant strains negative for mcr-1 to mcr-5 | ||||||
| CNR 111 J7 | 8 | PmrB (D14N, S71C, V83A) | 1.20 ± 1.00 | 0.40 ± 0.50 | 0.80 ± 0.50 | |
| CNR 20160039 | 4 | Unknown | Penicillinase | 1.40 ± 0.20 | 0.50 ± 0.10 | 0.90 ± 0.10 |
| CNR 20160235 | 4 | MgrB (V8A) | 0.90 ± 0.31 | 0.00 ± 0.00 | 0.90 ± 0.31 | |
| CNR 1728 | 8 | PmrB (G160E) | 1.20 ± 0.30 | 0.50 ± 0.10 | 0.70 ± 0.20 | |
| CNR 187 G3 | 4 | Unknown | NDM-5 | 0.10 ± 0.00 | 0.00 ± 0.00 | 0.10 ± 0.00 |
| CNR 189 E5 | 4 | Unknown | NDM-5 | 0.10 ± 0.00 | 0.00 ± 0.00 | 0.10 ± 0.00 |
| CNR 169 D6 | 4 | Unknown | OXA-48 | 0.20 ± 0.00 | 0.00 ± 0.00 | 0.20 ± 0.00 |
| CNR 165 J9 | 4 | Unknown | ESBLb | 0.90 ± 0.00 | 0.00 ± 0.00 | 0.90 ± 0.00 |
| CNR 196 G2 | 4 | Unknown | ESBL | 1.01 ± 0.35 | 1.01 ± 0.35 | 0.00 ± 0.00 |
| CNR 169 F2 | 8 | Unknown | 0.60 ± 0.10 | 0.00 ± 0.00 | 0.60 ± 0.10 | |
| CNR 198 E2 | 8 | Unknown | 0.40 ± 0.10 | 0.00 ± 0.00 | 0.40 ± 0.10 | |
| CNR 181 D5 | 16 | Unknown | VIM-1 | 0.70 ± 0.00 | 0.6 ± 0.00 | 0.10 ± 0.00 |
| Colistin-susceptible strains | ||||||
| J53 | 0.5 | 0.00 ± 0.00 | 0.00 ± 0.00 | 0.00 ± 0.00 | ||
| 1608071881 | 0.25 | 0.00 ± 0.00 | 0.00 ± 0.00 | 0.00 ± 0.00 | ||
| 1608075385 | 0.12 | Penicillinase | 0.00 ± 0.00 | 0.00 ± 0.00 | 0.00 ± 0.00 | |
| 1608078105 | 0.25 | Penicillinase | 0.00 ± 0.00 | 0.00 ± 0.00 | 0.00 ± 0.00 | |
| 2H6 | 0.25 | CTX-M-15 | 0.00 ± 0.00 | 0.00 ± 0.00 | 0.00 ± 0.00 | |
| 2E10 | 0.25 | CTX-M-14 | 0.00 ± 0.00 | 0.00 ± 0.00 | 0.00 ± 0.00 | |
| 1A6 | 0.25 | NDM-4, CTX-M-15, OXA-1 | 0.00 ± 0.00 | 0.00 ± 0.00 | 0.00 ± 0.00 | |
| 1C2 | 0.5 | VIM-1 | 0.00 ± 0.00 | 0.00 ± 0.00 | 0.00 ± 0.00 | |
| 2A1 | 0.25 | OXA-48, CTX-M-15 | 0.00 ± 0.00 | 0.00 ± 0.00 | 0.00 ± 0.00 |
Values shown are the mean ± standard deviation of three independent experiments. Where known, the genetic basis of resistance is indicated (resistance mechanism). PRR values were calculated by summing the intensities of the lipid A peaks attributable to the addition of pETN (m/z 1,919.2) and l-Ara4N (m/z 1,927.2) and dividing this number by the intensity of the peak corresponding to native lipid A (m/z 1,796.2) (PRR = [m/z 1,919.2 intensity + m/z 1,927.2 intensity]/m/z 1,796.2 intensity). PRR1,919 and PRR1,927 indicate the contributions of specific lipid A modifications (pETN and/or l-Ara4N) to the overall PRR value. PRR1,919 and PRR1,927 were calculated by dividing the intensity of the peak at the appropriate m/z value (m/z 1,919.2 and m/z 1,927.2 for pETN and l-Ara4N addition, respectively) by the intensity of the peak corresponding to native lipid A (m/z 1,796.2).
ESBL, extended-spectrum β-lactamase.