Table 3.
Cumulative results of amino acid substitutions in various genes contributing to colistin resistance found upon WGS analysis of two non-MCR colistin-resistant XDR K. pneumoniae strains.
| Genes | Isolate-53 | Isolate-62 | ||||
|---|---|---|---|---|---|---|
| Mutation | PROVEAN score | Prediction (cut off = −2.5) | Mutation | PROVEAN score | Prediction (cut off = −2.5) | |
| pmrA (transcriptional regulatory protein PmrA) | G53V | -7.575 | Deleterious | A217V | -0.729 | Neutral |
| A217V | -0.729 | Neutral | ||||
| pmrB (Sensor protein PmrB) | A246T | -1.132 | Neutral | A246T | -1.132 | Neutral |
| M213L | -0.623 | Neutral | T157P | -5.787 | Deleterious | |
| M213L | -0.623 | Neutral | ||||
| pmrC/ eptA (Lipid A phosphoethanolamine transferase) | S25G | -1.726 | Neutral | S25G | -1.726 | Neutral |
| Q319R | -1.735 | Neutral | Q319R | -1.735 | Neutral | |
| F27C | -2.411 | Neutral | F27C | -2.411 | Neutral | |
| pmrE/ugd (UDP-glucose 6-dehydrogenase) | I17V | -0.008 | Neutral | I17V | -0.008 | Neutral |
| mgrB (PhoP/PhoQ regulator) | G37C | -9.000 | Deleterious | G37C | -9.000 | Deleterious |
| arnB (UDP-4-amino-4-deoxy-L-arabinose--oxoglutarate | A112D | 0.683 | Neutral | A112D | 0.683 | Neutral |
| S150P | 1.430 | Neutral | S150P | 1.430 | Neutral | |
| aminotransferase) | V168I | 0.203 | Neutral | V168I | 0.203 | Neutral |
| S280T | -1.149 | Neutral | S280T | -1.149 | Neutral | |
| arnC (Undecaprenyl-phosphate 4-deoxy-4-formamido-L-arabinose transferase) | A32T | -1.050 | Neutral | A32T | -1.050 | Neutral |
| A115E | -1.351 | Neutral | A115E | -1.351 | Neutral | |
| T139S | -1.383 | Neutral | T139S | -1.383 | Neutral | |
| I286V | -0.461 | Neutral | I286V | -0.461 | Neutral | |
| arnT (Undecaprenyl phosphate-alpha-4-amino-4-deoxy-L-arabinose arabinosyl transferase) | L114M I117V | -0.942 | Neutral | L114M I117V | -0.942 | Neutral |
| S164G | 0.037 | Neutral | S164G | 0.037 | Neutral | |
| M177I | 2.646 | Neutral | M177I | 2.646 | Neutral | |
| K372R | -3.810 | Deleterious | K372R | -3.810 | Deleterious | |
| 0.301 | Neutral | 0.301 | Neutral | |||
| arnA_FT (Bifunctional polymyxin resistance protein ArnA) | H363N | -3.981 | Deleterious | H363N | -3.981 | Deleterious |
| T185A | 0.119 | Neutral | T185A | 0.119 | Neutral | |
| pagP (Lipid A palmitoyltransferase PagP) | Addition of 2 amino acid at N-terminal, F to I at C-terminal | Deletion of 17 amino acid at N-terminal, F to I at C-terminal | ||||
| Efflux pump AcrAB | + | + | ||||
| Spermidine export protein MdtI)/KpnF | + | + | ||||
PROVEAN score is a measure of the change in protein structure: if the score is equal or below to the predefined threshold (cut off = −2.5), the variant is predicted to have a ‘deleterious’ effect; if above, the variant is predicted to have a ‘neutral’ effect. In the latter column, there is a prediction of the mutation effect on the protein functionality.