Characterization of an ATP-binding cassette from Clostridium perfringens with homology to an ABC transporter from Clostridium hathewayi.
A ciprofloxacin-resistant mutant of Clostridium perfringens, strain VPI-C, which had stable mutations in the topoisomerase genes, accumulated less norfloxacin and ethidium bromide than the wild type, strain VPI. Efflux pump inhibitors both increased the accumulation of ethidium bromide by cells of the mutant and enhanced their sensitivity to this toxic dye. Cloning a gene, which codes for a putative ABC transporter protein (NP_562422) of 527 amino acids, from the mutant strain VPI-C into the wild-type strain VPI not only reduced the accumulation of ethidium bromide by the recombinant strain but also reduced its sensitivity to norfloxacin and ciprofloxacin. Efflux pump inhibitors decreased the rate at which ethidium bromide was removed from the cells of the recombinant strain. It appears that the putative ABC transporter protein (NP_562422) may contribute to extrusion of drugs from C. perfringens.
Rafii
Fatemeh
F
Division of Microbiology, National Center for Toxicological Research, FDA, Jefferson, AR 72079, USA. fatemeh.rafii@fda.hhs.gov
Park
Miseon
M
Carman
Robert J
RJ
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D003013:Clostridium / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D003016:Clostridium perfringens / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D024901:Drug Resistance, Multiple, Bacterial; D004996:Ethidium / Q000378:metabolism / Q000494:pharmacology; D024841:Fluoroquinolones / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009643:Norfloxacin / Q000378:metabolism / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid
D018528:ATP-Binding Cassette Transporters; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D024841:Fluoroquinolones; D004996:Ethidium; D009643:Norfloxacin