The Library
Data for A traceless reversible polymeric colistin prodrug to combat multidrug-resistant (MDR) gram-negative bacteria
Tools
Zhu, Chongyu, Schneider, Elena K., Wang, Jiping, Kempe, Kristian, Wilson, Paul, Velkov, Tony, Li, Jian, Davis, Thomas P., Whittaker, Michael R. and Haddleton, David M. (2017) Data for A traceless reversible polymeric colistin prodrug to combat multidrug-resistant (MDR) gram-negative bacteria. [Dataset]
Archive (ZIP) (Biological, GPC, HPLC, MALDI-ToF, NMR data)
Archived+Zhu-ColPEG-JCR.zip - Unspecified Version Available under License Creative Commons Attribution 4.0. Download (254Mb) |
Official URL: http://wrap.warwick.ac.uk/86868
Abstract
Colistin methanesulfonate (CMS) is the only prodrug of colistin available for clinical use for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria. Owing to its slow and variable release, an alternative is urgently required to improve effectiveness. Herein we describe a PEGylated colistin prodrug whereby the PEG is attached via a cleavable linker (col-aaPEG) introducing an acetic acid terminated poly (ethylene glycol) methyl ether (aaPEG) onto the Thr residue of colistin. Due to the labile ester containing link, this prodrug is converted back into active colistin in vitro within 24 h. Compared to CMS, it showed a similar or better antimicrobial performance against two MDR isolates of Pseudomonas aeruginosa and Acinetobacter baumannii through in vitro disk diffusion, broth dilution and time-kill studies. In a mouse infection model, col-aaPEG displayed acceptable bacterial killing against P. aeruginosa ATCC 27853 and no nephrotoxicity was found after systemic administration, suggesting it to be a potential alternative for CMS.
Item Type: | Dataset | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Subjects: | Q Science > QR Microbiology | |||||||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | |||||||||||||||
Type of Data: | Instrument measurement, Excel, Word, PowerPoint, Bitmap, PNG | |||||||||||||||
Library of Congress Subject Headings (LCSH): | Gram-negative bacteria, Multidrug resistance, Bacterial diseases -- Treatment | |||||||||||||||
Journal or Publication Title: | Journal of Controlled Release | |||||||||||||||
Publisher: | University of Warwick, Department of Chemistry | |||||||||||||||
ISSN: | 01683659 | |||||||||||||||
Official Date: | 10 March 2017 | |||||||||||||||
Dates: |
|
|||||||||||||||
DOI: | 10.1016/j.jconrel.2017.02.005 | |||||||||||||||
Status: | Not Peer Reviewed | |||||||||||||||
Publication Status: | Published | |||||||||||||||
Media of Output (format): | .docx .xlsx .pptx .txt | |||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||
Copyright Holders: | University of Warwick | |||||||||||||||
Description: | PEG Compounds Disk Diffusion Assay – 20150715 HY/JA 3 compounds were supplied by Chongyu on 19/06/2015: Stock solutions of 1 mg/mL were made based on the sheet detailing the weights of compounds. Due to limited amount of PEG-1, PEG-1 was not filter sterilized. A negative control was included for PEG-1. mPEG-AA and Colistin were filter sterilised through 0.2 μm membrane filter. Remaining stock solutions were stored at room temperature. All compounds were dissolved in F/S MQH2O. Added 10 μL and 20 μL of 1 mg/mL stock onto a blank disk (Oxoid). Test concentrations Test isolates were matched to a 0.5 McFarland standard before being swabbed onto nutrient agar. Controls used were: 10μg Colistin and 10μL F/S MQH2O. The sizes of the zones of inhibition are shown in Table 1. The diameter is measured in mm and the zone of inhibition of the disk (6 mm) is included in the ZOI measurement. Table 1. The size of the zone of inhibition (diameter in mm) of 3 different isolates incubated with 10μg and 20μg of test compound. Pictures taken by ProtoCOL 3 P. aeruginosa ATCC 27853 PEG Compounds: Minimum inhibitory concentration by microbroth dilution – 20150715 HY/JA Stock solutions from DDA were used and diluted in CAMHB according to the tables on page 5 and 6. PEG-1 was tested up to 16 mg/L due to the limited amount available. PEG-2, mPEG-AA and Colistin were tested up to 128 mg/L. Plates were incubated at 37oC and read at 20hrs incubation. Preparation of medium containing PEG-1, (Adaptation from SOP0028 for lipopeptide MIC screening). Enough solution for 1x 96 well plates Preparation of medium containing PEG-2, mPEG-AA, Colistin, (Adaptation from SOP0028 for lipopeptide MIC screening). Enough solution for 1x 96 well plates |
|||||||||||||||
Date of first compliant deposit: | 22 February 2017 | |||||||||||||||
Date of first compliant Open Access: | 23 February 2017 | |||||||||||||||
RIOXX Funder/Project Grant: |
|
|||||||||||||||
Related URLs: | ||||||||||||||||
Contributors: |
|
Request changes or add full text files to a record
Repository staff actions (login required)
View Item |
Downloads
Downloads per month over past year