A DHA14 drug efflux gene from Xanthomonas albilineans confers high-level albicidin antibiotic resistance in Escherichia coli

Bostock, J. M., Huang, G., Hashimi, S. M., Zhang, L. and Birch, R. G. (2006) A DHA14 drug efflux gene from Xanthomonas albilineans confers high-level albicidin antibiotic resistance in Escherichia coli. Journal of Applied Microbiology, 101 1: 151-160.


Author Bostock, J. M.
Huang, G.
Hashimi, S. M.
Zhang, L.
Birch, R. G.
Title A DHA14 drug efflux gene from Xanthomonas albilineans confers high-level albicidin antibiotic resistance in Escherichia coli
Journal name Journal of Applied Microbiology   Check publisher's open access policy
ISSN 1364-5072
Publication date 2006
Sub-type Article (original research)
DOI 10.1111/j.1365-2672.2006.02899.x
Volume 101
Issue 1
Start page 151
End page 160
Total pages 10
Editor Arthur Gilmore
Place of publication Oxford
Publisher Blackwell Publishing
Collection year 2006
Language eng
Subject C1
270000 Biological Sciences
780105 Biological sciences
Abstract Aims: Identification of a gene for self-protection from the antibiotic-producing plant pathogen Xanthomonas albilineans, and functional testing by heterologous expression. Methods and Results: Albicidin antibiotics and phytotoxins are potent inhibitors of prokaryote DNA replication. A resistance gene (albF) isolated by shotgun cloning from the X. albilineans albicidin-biosynthesis region encodes a protein with typical features of DHA14 drug efflux pumps. Low-level expression of albF in Escherichia coli increased the MIC of albicidin 3000-fold, without affecting tsx-mediated albicidin uptake into the periplasm or resistance to other tested antibiotics. Bioinformatic analysis indicates more similarity to proteins involved in self-protection in polyketide-antibiotic-producing actinomycetes than to multi-drug resistance pumps in other Gram-negative bacteria. A complex promoter region may co-regulate albF with genes for hydrolases likely to be involved in albicidin activation or self-protection. Conclusions: AlbF is the first apparent single-component antibiotic-specific efflux pump from a Gram-negative antibiotic producer. It shows extraordinary efficiency as measured by resistance level conferred upon heterologous expression. Significance and Impact of the Study: Development of the clinical potential of albicidins as potent bactericidial antibiotics against diverse bacteria has been limited because of low yields in culture. Expression of albF with recently described albicidin-biosynthesis genes may enable large-scale production. Because albicidins are X. albilineans pathogenicity factors, interference with AlbF function is also an opportunity for control of the associated plant disease.
Keyword Albicidin
Antibiotic Resistance
Dha14
Drug Efflux Pump
Xanthomonas Albilineans
Biotechnology & Applied Microbiology
Microbiology
Major Facilitator Superfamily
Molecular Characterization
Transcriptional Analysis
Bacillus-subtilis
Biosynthesis
Streptomyces
Sugarcane
Cluster
Protein
Pumps
Q-Index Code C1

 
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