Table 5.
Overview of residues of interest in the DBP area of 19 selected RND-type MDR transporters, and conservation among 135 pumps.
| Position | 136 | 178 | 610 | 615 | 617 | 628 | 46 | 89 | 128 | 130 | 134 | 135 | 139 | 151 | 176 | 177 | 180 | 273 | 274 | 276 | 277 | 279 | 288 | 290 | 292 | 327 | 571 | 573 | 612 | 620 | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Pump | |||||||||||||||||||||||||||||||
| AcrB-Ec | F | F | F | F | F | F | S | Q | S | E | S | S | V | Q | Q | L | S | E | N | D | I | A | G ** | G | K | Y | V | M | V | R | |
| Conservation (%) | 49 | 70 | 50 | 60 | 52 | 74 | 38 | 38 | 18 | 27 | 40 | 32 | 50 | 22 | 59 | 44 | 34 | 55 | 31 | 29 | 10 | 40 | 49 | 43 | 33 | 81 | 29 | 24 | 44 | 19 | |
| AcrB-Sa | F | F | F | F | F | F | S | Q | S | E | S | S | V | Q | Q | L | S | E | N | D | V | A | G *** | G | K | Y | V | M | V | R | |
| AcrF-Sa | F | F | F | F | F | F | S | T | S | E | S | S | V | Q | Q | L | A | E | N | N | V | A | G | G | K | Y | V | L | V | Q | |
| AcrF-Ec | Y | F | F | F | F | F | S | T | S | E | S | S | V | Q | Q | L | A | E | N | N | V | A | G | G | K | Y | V | L | V | Q | |
| MexB-Pa | F | F | F | F | F | F | Q | T | R | T | K | N | V | K | Q | V | S | Q | D | S | I | A | G | A | K | Y | V | F | V | R | |
| AcrD-Ec | N | Y | F | S | P | F | T | S | T | R | D | T | T | K | D | A | S | E | K | D | Y | S | G | G | K | Y | M | T | T | N | |
| AcrD-Sa | N | Y | F | S | P | F | T | T | T | R | D | T | T | K | D | A | S | E | K | D | Y | S | G | G | K | Y | M | T | T | N | |
| MexY-Pa | I | W | Y | F | L | F | S | S | Y | E | D | S | I | A | E | T | A | S | E | G | F | S | G **** | A | K | Y | D | M | V | D | |
| MexD-Pa | F | F | F | F | F | F | T | E | Q | E | A | G | I | T | Q | F | S | E | S | N | I | S | G | A | Q | Y | Y | V | I | Q | |
| AdeB-Ab | F | F | T | W | F | F | S | E | Q | E | S | G | L | E | Q | S | A | Q | A | N | F | I | A | A | Q | Y | W | M | I | A | |
| AdeJ-Ab | F * | F | F | F | F | F | A | S | T | T | A | S | V | D | Q | V | G | D | N | Q | F | S | G * | A | K | Y | V | M | V | V | |
| MtrD-Ng | F | F | I | F | F | F | H | S | T | S | S | N | I | T | R | L | A | E | D | S | S | T | G | A | M | Y | F | M | V | S | |
| MexQ-Pa | I | W | V | L | V | F | T | I | V | Q | P | D | V | P | V | V | A | D | A | A | L | S | A | Q | I | Y | Y | V | F | F | |
| MexF-Pa | L | F | V | L | I | F | R | T | T | D | P | D | V | M | Q | L | L | N | Q | A | L | S | A | P | F | Y | Y | V | F | F | |
| AdeG-Ab | L | F | V | L | I | F | R | T | T | L | P | T | V | M | G | L | S | S | Q | G | L | S | A | P | F | Y | Y | I | F | F | |
| MexI-Pa | A | F | – | W | I | G | T | V | E | S | T | T | Y | I | Q | T | G | A | A | E | T | A | H | G | F | Y | A | L | – | T | |
| LpeB-Lp | G | W | – | L | F | V | S | Q | E | Q | S | N | F | F | E | V | – | D | N | Q | M | V | V | S | N | I | L | G | – | D | |
| AcrB-Hi | G | F | – | M | I | I | S | T | S | S | G | S | Y | S | Q | V | A | E | N | N | S | A | V | A | N | Y | A | I | – | A | |
| MexW-Pa | A | L | – | F | I | G | T | T | Q | E | A | S | Y | N | E | I | N | A | S | D | A | S | Y | G | K | Y | I | F | – | Y | |
Asterisks: * (F→L) and (G→S) found in AdeJ from Acinetobacter baumannii—in experimentally evolved and clinical strains from Australia implicated in meropenem resistance [77,78]; ** (G→C) found in experimentally evolved AcrB from Escherichia coli—increases efflux, especially for erythromycin [79]; *** (G→D) found in AcrB from Salmonella Typhimurium—in experimentally evolved and clinical strains from the UK, implicated in ciprofloxacin resistance [80,81]; **** (G→A/S) found in MexY from Pseudomonas aeruginosa—in clinical strains mainly from the EU and Australia, implicated in tobramycin resistance [82,83,84]. Colors: green background, conserved residues compared to AcrB-Ec; red background, bulky Trp (potentially) inhibiting inhibitor (EPI) effectiveness. The first six separated columns show the Phe residues (as in AcrB-Ec) in the “hydrophobic pit”. Note: Salmonella AcrB, AcrD and AcrF alignments based on Salmonella Typhi str. CT18 genes STY0519 and STY2719 and Salmonella Typhi str. LT2 gene STM3391, respectively. LpeB-Lp alignment based on Legionella pneumophila str. Paris gene lpp2880. Conservation based on 135 pumps, and further details (regarding alternative residues and the conservation percentages) can be found in Table S1.