Antibiotic susceptibility profiles of Escherichia coli strains lacking multidrug efflux pump genes.
The contribution of seven known and nine predicted genes or operons associated with multidrug resistance to the susceptibility of Escherichia coli W3110 was assessed for 20 different classes of antimicrobial compounds that include antibiotics, antiseptics, detergents, and dyes. Strains were constructed with deletions for genes in the major facilitator superfamily, the resistance nodulation-cell division family, the small multidrug resistance family, the ATP-binding cassette family, and outer membrane factors. The agar dilution MICs of 35 compounds were determined for strains with deletions for multidrug resistance (MDR) pumps. Deletions in acrAB or tolC resulted in increased susceptibilities to the majority of compounds tested. The remaining MDR pump gene deletions resulted in increased susceptibilities to far fewer compounds. The results identify which MDR pumps contribute to intrinsic resistance under the conditions tested and supply practical information useful for designing sensitive assay strains for cell-based screening of antibacterial compounds.
Genome Therapeutics Corporation, Waltham, Massachusetts, USA.
M C
MC
Sulavik
C
C
Houseweart
C
C
Cramer
N
N
Jiwani
N
N
Murgolo
J
J
Greene
B
B
DiDomenico
K J
KJ
Shaw
G H
GH
Miller
R
R
Hare
G
G
Shimer
D000891:Anti-Infective Agents, Local / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D004396:Coloring Agents / Q000494:pharmacology; D003902:Detergents / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D029968:Escherichia coli Proteins; D019450:Genes, MDR; D026901:Membrane Transport Proteins; D008826:Microbial Sensitivity Tests; D017384:Sequence Deletion
D000891:Anti-Infective Agents, Local; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D004396:Coloring Agents; D003902:Detergents; D029968:Escherichia coli Proteins; D026901:Membrane Transport Proteins; C073126:tolC protein, E coli