TABLE 1.
Strain | MexT substitution (304 aaa) | Transcript levelb |
MIC (μg · ml−1)c |
Reference or source | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|
mexEd | oprD | mexB | CIP | CHL | TMP | IMP | MEM | ATM | |||
Clinical strains | |||||||||||
4177 | R166H | 20 | NDe | 0.6 | 0.5 | 1,024 | 1,024 | 16 | 2 | 32 | 6 |
4088 | G257S | 112 | ND | 0.4 | 1 | 2,048 | >2,048 | 8 | 0,25 | 1 | 6 |
10-12 | G257A | 26 | NRf | 9.2 | 2 | 128 | >2,048 | 16 | ND | 32 | 8 |
0810 | G258D | 32 | ND | ND | 8 | 1,024 | 1,024 | 4 | 1 | ND | 7 |
1510 | Y138D plus G258D | 21 | ND | ND | 2 | 256 | 512 | 16 | 8 | ND | 7 |
Complemented PA14 derivatives | |||||||||||
PA14 | WTg | 1 | 1 | 1 | 0.125 | 64 | 64 | 1 | 0.5 | 4 | F. Ausubel |
PA14ΔmexS | WT | 192 ± 9.2 | 0.3 ± 0.1 | 0.4 ± 0.2 | 2 | 2,048 | >2,048 | 4 | 2 | 2 | 7 |
PA14ΔmexT | −h | 0.4 ± 0.1 | 1.7 ± 0.2 | 2.2 ± 0.2 | 0.125 | 32 | 32 | 1 | 0.5 | 4 | This study |
PA14ΔmexTPA14 | WT | 2.2 ± 0.7 | 1.1 ± 0.1 | 1.4 ± 0.2 | 0.125 | 64 | 64 | 1 | 0.5 | 4 | This study |
PA14ΔmexT4177 | R166H | 3.2 ± 0.3 | 2.0 ± 0.2 | 2.6 ± 0.1 | 0.125 | 64 | 64 | 1 | 0.5 | 4 | This study |
PA14ΔmexT4088 | G257S | 189 ± 5.9 | 0.4 ± 0.1 | 0.9 ± 0.1 | 2 | 2,048 | >2,048 | 2 | 1 | 2 | This study |
PA14ΔmexT10-12 | G257A | 110 ± 3.6 | 0.4 ± 0.1 | 0.9 ± 0.1 | 1 | 1,024 | 1,024 | 2 | 1 | 2 | This study |
PA14ΔmexT0810 | G258D | 1.9 ± 0.4 | 0.9 ± 0.1 | 1.4 ± 0.1 | 0.125 | 64 | 64 | 1 | 0.5 | 4 | This study |
PA14ΔmexT1510 | Y138D plus G258D | 6.3 ± 0.2 | 0.9 ± 0.1 | 1.4 ± 0.1 | 0.25 | 64 | 64 | 1 | 0.5 | 4 | This study |
aa, amino acids.
Mean gene expression values were calculated from two independent bacterial cultures, each of which was assayed in duplicates. They are expressed as a ratio to the gene transcription level in wild-type reference strain PA14.
CIP (ciprofloxacin), CHL (chloramphenicol), and TMP (trimethoprim) are substrates of MexEF-OprN. IMP (imipenem) and MEM (meropenem) are substrates of porin OprD (corepressed with mexEF-oprN overexpression). ATM (aztreonam) is a substrate of MexAB-OprM.
Significant overexpression of mexE (threshold fixed at 20-fold) and increase in resistance to MexEF-OprN substrates is indicated in boldface type.
ND, not determined.
NR, not relevant because of a codon stop in the oprD gene.
WT, wild type.
−, deleted gene.