Biol. Pharm. Bull. 29(3) 550—553 (2006)

نویسندگان

  • S. Alberti
  • L. Martinez-Martinez
  • A. Pascual
چکیده

ratory infection. It causes nosocomial infections in immunocompromised hosts. Recent studies indicate that an increasing percentage of Klebsiella strains are becoming resistant to multiple antimicrobial agents. In particular, infection with K. pneumoniae that are resistant against the b-lactams and fluoroquinolones are especially severe clinical problems. Furthermore, such resistant K. pneumoniae are often resistant against other multiple antimicrobial agents of unrelated structures. Multidrug efflux pumps are often involved in such multiple resistances. Multidrug efflux pumps in Escherichia coli, a bacterium closely related to K. pneumoniae, are well analyzed and characterized. It has been reported that 38 genes or operons for multidrug efflux pumps would be present in the chromosome of E. coli. In fact, 19 of them have been reported to be involved in drug resistance. Thirtyfour genes or operons that code for multidrug efflux pumps have been suggested in the chromosome of Pseudomonas aeruginosa. Disruption of genes for multidrug efflux pumps resulted in a great decrease in the resistance against multiple antimicrobial agents in E. coli 12,13) and P. aeruginosa. These results support the idea that multidrug efflux pumps are very important for the bacterial escape from the toxicity of many antimicrobial agents. So far, multidrug efflux pumps have not been well investigated for K. pneumoniae. Only two multidrug efflux pumps, AcrAB and QacE (including DQacE), have been reported with K. pneumoniae (A. Domenech-Sanchez, S. Alberti, L. Martinez-Martinez, A. Pascual, I. Gar-cia, and V. J. Benedi, Abstr. 41st Intersci. Conf. Antimicrob. Agents Chemother. abstr. C1-2018, p. 104, 2001). Recently, the sequencing of the whole genome of K. pneumoniae strain MGH78578 was completed (http://genomeold.wustl.edu/projects/bacterial/kpneumoniae/). Based on the sequences, we estimated that there would be more than 30 genes or operons for multidrug efflux pumps in the chromosome of K. pneumoniae. We have been trying to clone many of such genes or operons, and in fact cloned more than 10 genes or operons responsible for multidrug resistance. We found that one of the genes, designated kmrA, coded for a multidrug efflux pump. Here we characterized the KmrA pump. We also cloned a gene for its homologue from Salmonella enterica, and characterized the pump.

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تاریخ انتشار 2006