Expression of beta-glucuronidase on the surface of bacteria enhances activation of glucuronide prodrugs

doi:10.1038/cgt.2013.17

CNU IR > Pharmacy and Science > Dept. of Pharmacy > Periodical Articles > Item 310902800/27846

Please use this identifier to cite or link to this item: https://ir.cnu.edu.tw/handle/310902800/27846

Title:	Expression of beta-glucuronidase on the surface of bacteria enhances activation of glucuronide prodrugs
Authors:	Cheng, C-M Chen, F. M. Lu, Y-L Tzou, S-C Wang, J-Y Kao, C-H Liao, K-W Cheng, T-C Chuang, C-H Chen, B-M Roffler, S. Cheng, T-L
Contributors:	藥學系
Keywords:	Beta-Glucuronidase Autotransporter Protein Adhesin Bacteria-Directed Enzyme Prodrug Therapy Extracellular Activation Surface Display
Date:	2013-05
Issue Date:	2014-05-26 10:46:03 (UTC+8)
Publisher:	Nature Publishing Group
Abstract:	Extracellular activation of hydrophilic glucuronide prodrugs by p-glucuronidase (beta G) was examined to increase, the therapeutic, efficacy of bacteria-directed enzyme prodrug therapy (BDEPT). beta G was expressed on the surface of Escherichia coli by fusion to either the bacterial autotransporter protein Adhesin (membrane beta G (m beta G)/AIDA) or the lipoprotein (Ipp) outermembrane protein A (m beta G/Ipp). Both m beta G/AIDA and m beta G/Ipp were expressed on the bacterial surface, but only m beta G/AIDA displayed enzymatic activity. The rate of substrate hydrolysis by m beta G/AIDA-BL21 cells was 2.6-fold greater than by p beta G-BL21 cells, which express periplasmic beta G. Human colon cancer HCT116 cells that were incubated with m beta G/AIDA-BL21 bacteria were sensitive to a glucuronide prodrug (p-hydroxy aniline mustard beta-D-glucuronide, HAMG) with an half maximal inhibitory concentration (IC50) value of 226.53 +/- 45.4 M, similar to the IC50 value of the active drug (p-hydroxy aniline mustard, pHAM; 70.6 +/- 6.75 mu M), indicating that m beta G/AIDA on BL21 bacteria could rapidly and efficiently convert HAMG to an active anticancer agent. These results suggest that surface display of functional beta G on bacteria can enhance the hydrolysis of glucuronide prodrugs and may increase the effectiveness of BDEPT.
Relation:	Cancer Gene therapy, v.20 n.5, pp.276-281
Appears in Collections:	[Dept. of Pharmacy] Periodical Articles

Files in This Item:

File	Description	Size	Format
index.html		0Kb	HTML	1478	View/Open

Loading...