Table 2. Characterization of laboratory-evolved tigecycline-resistant K. pneumoniae and single-step selection of K. pneumoniae mutants.
| Strain | Parental strain | Putative mutation(s) causing reduced susceptibility to TGC | Other genetic changes | TGC MIC (mg/L) | TGC MIC (mg/L) +PaβN (50 mg/L) | Relative growth rate | Lag time (min) | TET | CHL | AK | CTX | CIP | IPM | NI |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| XH209 | NA | NA | NA | 2 | 2 | 1 | 120 | >256 | >256 | 2 | >256 | 0.75 | 4 | 64 |
| XH210 | XH209 | ramR Q122* | NA | 16 | 8 | 0.98 | 113.44 | >256 | >256 | 2 | >256 | 4 | 4 | 192 |
| XH211 | XH209 | ramA Q72L, lon Q317* ramR Δ190 bp (322–511) | cspE N57K | 128 | 8 | 0.42 | 232 | >256 | >256 | 1 | 1.5 | 3 | 0.125 | 3 |
| XH212 | XH209 | PramR +G, lon D445V, rpsJ V57L | tetA I235F, 300 kb dup | >256 | 256 | 0.59 | 183.75 | >256 | >256 | 1.5 | >256 | 6 | 4 | 16 |
| XH213 | XH209 | ramR A40T, lon R33W, rpoC Δ18 bp (634–651) | eutL E95Q | >256 | 64 | 0.46 | 223.44 | >256 | >256 | 0.5 | 128 | 3 | 4 | 8 |
| XH214 | XH209 | ramR L58P, rpoC G336A | 64 | 32 | 0.74 | 189.06 | >256 | >256 | 0.75 | >256 | 2 | 1 | 128 | |
| XH215 | XH209 | ramR Q135*, lon Δ9 bp (791–799), rpoC S263Y | yfiR C89Y hypo K302T | 256 | 64 | 0.56 | 187.19 | >256 | >256 | 0.75 | 64 | 3 | 2 | 4 |
| XH216 | XH209 | ramR S29*, lon N417K | Mobile element protein G12E | 64 | 16 | 0.55 | 241.25 | >256 | >256 | 0.75 | 128 | 2 | 6 | 4 |
| XH490 | XH209 | ramR Q122* | ND | 16 | ND | 0.98 | 123.75 | >256 | >256 | 1.5 | >256 | 3 | 8 | 128 |
| XH491 | XH209 | ramR T42Ins (8 bp) | ND | 8 | ND | 0.98 | 120 | >256 | >256 | 1 | >256 | 3 | 6 | 128 |
| XH492 | XH209 | ramR S137* | ND | 16 | ND | 0.98 | 113.44 | >256 | >256 | 1 | >256 | 3 | 3 | 192 |
| XH493 | XH209 | ramR A49Ins (8 bp) | ND | 16 | ND | 0.97 | 232 | >256 | 64 | 1 | >256 | 3 | 3 | >512 |
| XH494 | XH209 | ramR M1V | ND | 16 | ND | 0.99 | 183.75 | >256 | >256 | 1 | >256 | 2 | 4 | 96 |
| XH495 | XH209 | ramR W185* | ND | 16 | ND | 0.97 | 223.44 | >256 | 32 | 1.5 | >256 | 4 | 6 | 128 |
| XH496 | XH209 | ramR F45Del (8 bp) | ND | 16 | ND | 0.88 | 189.06 | >256 | >256 | 1.5 | >256 | 2 | 1 | 32 |
| XH497 | XH209 | ramR A2FS | ND | 8 | ND | 0.98 | 187.19 | >256 | >256 | 1.5 | >256 | 2 | 6 | 64 |
| XH498 | XH209 | ramR F45Ins (8 bp) | ND | 16 | ND | 0.99 | 241.25 | >256 | >256 | 1.5 | >256 | 2 | 3 | 128 |
| XH499 | XH209 | ramR R107H | ND | 16 | ND | 0.99 | 123.75 | >256 | >256 | 1.5 | >256 | 2 | 3 | 64 |
| XH500 | XH209 | ramR W89L | ND | 16 | ND | 0.98 | 123.75 | >256 | >256 | 2 | >256 | 3 | 2 | 96 |
| XH501 | XH209 | ramR A37V | ND | 8 | ND | 0.99 | 122.5 | >256 | >256 | 1.5 | >256 | 3 | 4 | 128 |
| XH502 | XH209 | ramR W89* | ND | 8 | ND | 0.97 | 115.31 | >256 | >256 | 1.5 | >256 | 3 | 6 | 128 |
| XH503 | XH209 | ramR T119P | ND | 8 | ND | 0.97 | 114.38 | >256 | >256 | 1.5 | >256 | 3 | 4 | 192 |
| XH504 | XH209 | ramR K5FS | ND | 8 | ND | 0.98 | 123.44 | >256 | >256 | 1.5 | >256 | 3 | 4 | 128 |
| XH505 | XH209 | ramR A105G | ND | 8 | ND | 0.97 | 124.06 | >256 | >256 | 1.5 | >256 | 3 | 4 | 128 |
TGC: tigecycline; TET: tetracycline; CHL: chloramphenicol; AK: amikacin; CTX: cefotaxime; CIP: ciprofloxacin; IPM: imipenem;NI: nitrofurantoin. Note: NA: not found;ND: not detect;
*: Stop codon;
Δ: Deletion; Ins: Insertion; Del: Deletion; FS: Frameshift;