Download Bacterial tumor therapy 최현일 Mailing address: Department of

Bacterial tumor therapy
최현일
Mailing address: Department of Microbiology, Chonnam National University Medical School,
5, Hak 1 dong, Dong-gu, Gwangju 501-746, Republic of Korea
E mail : [email protected]
Certain strains of bacteria, such as E. coli, Salmonella, and Clostridium, selectively
colonize and grow in tumors. We have demonstrated that E. coli and Salmonella spp are
capable of targeting both primary tumors and metastases, a feature that has been exploited for
tumor-selective drug delivery as well detection. To facilitate the monitoring of these strains in
vivo, bacteria have been engineered to express bioluminescence or fluorescence reporter
genes, which enabled investigators to track migration patterns and determine the fate of the
bacteria in a manner that is simple, non-invasive and amenable to repeated observations.
The abnormal vasculature of tumors is an important factor in bacterial targeting of
tumor tissue. Newly formed blood vessels in developing tumors are highly disorganized, with
incomplete endothelial linings and blind loops, resulting in sluggish blood flow and
inefficient delivery of nutrients and oxygen to regions within the tumor tissue. The
combination of poor nutrient delivery and oxygen starvation promotes the establishment of
non-proliferating hypoxic/anoxic cells within tumors, and might promote the growth of
obligatory and facultative anaerobic bacteria. We also observed that facultative anaerobic
bacteria, including E. coli and attenuated strains of S. typhimurium, colonize various types of
tumors, particularly the hypoxic or necrotic areas of the tumor. Based on these observations,
we reasoned that bacteria also have the potential to selectively localize and grow in the
infarcted myocardium. In the current study, we found that an attenuated strain of S.
typhimurium that is defective in ppGpp synthesis (ppGpp strain) selectively localizes to
infarcted myocardium. To exploit this bacterial tropism, we engineered the Salmonella
(ppGpp) to express and secrete a reporter protein specifically in infarcted myocardium
through the use of an inducible gene expression system.
Reference
Engineering and Visualization of Bacteria for Targeting Infarcted Myocardium.
Le, et al., Mol Ther. 2011 Mar 1
Genetically engineered Salmonella typhimurium as an imageable therapeutic probe for
cancer. Nguyen, et al., Cancer Res. 2010 Jan 1;70(1):18-23
Quantitative bioluminescence imaging of tumor-targeting bacteria in living animals.
Min, et al., Nat Protoc. 2008;3(4):629-36