Title
Resistance of the **Burkholderia cepacia** complex to fosmidomycin and fosmidomycin derivatives Resistance of the **Burkholderia cepacia** complex to fosmidomycin and fosmidomycin derivatives
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Amsterdam ,
Subject
Human medicine
Source (journal)
International journal of antimicrobial agents. - Amsterdam
Volume/pages
38(2011) :3 , p. 261-264
ISSN
0924-8579
ISI
000293593400010
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Abstract
The Burkholderia cepacia complex (BCC) is a group of 17 closely related opportunistic pathogens that are able to infect the respiratory tract of cystic fibrosis patients. BCC bacteria are intrinsically resistant to many antibiotics and are therefore difficult to eradicate. Fosmidomycin could be a new therapeutic agent to treat BCC infections as it inhibits 1-deoxy-d-xylulose-5-phosphate reductoisomerase (Dxr), a key enzyme in the non-mevalonate pathway essential in BCC bacteria for isoprenoid synthesis. In this study, the antimicrobial activity of fosmidomycin and eight fosmidomycin derivatives towards 40 BCC strains was investigated. All BCC strains were resistant to fosmidomycin, although addition of glucose-6-phosphate reduced the minimum inhibitory concentration values of FR900098, the fosmidomycin acetyl derivative, from 512 mg/L to 64 mg/L for Burkholderia multivorans and B. cepacia. This enhanced activity was linked to increased expression of the genes involved in glycerol-3-phosphate transport, which appears to be the only route for fosmidomycin import in BCC bacteria. Furthermore, upregulation of a fosmidomycin resistance gene (fsr) encoding an efflux pump was observed during fosmidomycin and FR900098 treatment. These results strongly suggest that the observed resistance in BCC bacteria is due to insufficient uptake accompanied by fosmidomycin and FR900098 efflux.
E-info
https://repository.uantwerpen.be/docman/iruaauth/68c1d7/62a19453c79.pdf
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