Dataset Information

Genetically engineered probiotics as catalytic glucose depriver for tumor starvation therapy.

ABSTRACT: Cancer cells predominantly adapt the frequent but less efficient glycolytic process to produce ATPs rather than the highly efficient oxidative phosphorylation pathway. Such a regulated metabolic pattern in cancer cells offers promising therapeutic opportunities to kill tumors by glucose depletion or glycolysis blockade. In addition, to guarantee tumor-specific therapeutic targets, effective tumor-homing, accumulation, and retention strategies toward tumor regions should be elaborately designed. In the present work, genetically engineered tumor-targeting microbes (transgenic microorganism EcM-GDH (Escherichia coli MG1655) expressing exogenous glucose dehydrogenase (GDH) have been constructed to competitively deprive tumors of glucose nutrition for metabolic intervention and starvation therapy. Our results show that the engineered EcM-GDH can effectively deplete glucose and trigger pro-death autophagy and p53-initiated apoptosis in colorectal tumor cells/tissues both in vitro and in vivo. The present design illuminates the promising prospects for genetically engineered microbes in metabolic intervention therapeutics against malignant tumors based on catalytically nutrient deprivation, establishing an attractive probiotic therapeutic strategy with high effectiveness and biocompatibility.

SUBMITTER: Ji P

PROVIDER: S-EPMC9792908 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetically engineered probiotics as catalytic glucose depriver for tumor starvation therapy.

Ji Penghao P An Bolin B Jie Zhongming Z Wang Liping L Qiu Shuwen S Ge Changhao C Wu Qihui Q Shi Jianlin J Huo Minfeng M

Materials today. Bio 20221215

Cancer cells predominantly adapt the frequent but less efficient glycolytic process to produce ATPs rather than the highly efficient oxidative phosphorylation pathway. Such a regulated metabolic pattern in cancer cells offers promising therapeutic opportunities to kill tumors by glucose depletion or glycolysis blockade. In addition, to guarantee tumor-specific therapeutic targets, effective tumor-homing, accumulation, and retention strategies toward tumor regions should be elaborately designed. ...[more]

PMID: 36582449

Similar Datasets

Project description:BackgroundMany preclinical studies have demonstrated the effectiveness of genetically modified probiotics (gm probiotics) in animal models of inflammatory bowel disease (IBD).ObjectiveThis systematic review was performed to investigate the role of gm probiotics in treating IBD and to clarify the involved mechanisms.MethodsPubMed, Web of Science, Cochrane Library, and Medline were searched from their inception to 18 September 2022 to identify preclinical and clinical studies exploring the efficacy of gm probiotics in IBD animal models or IBD patients. Two independent researchers extracted data from the included studies, and the data were pooled by the type of study; that is, preclinical or clinical.ResultsForty-five preclinical studies were included. In these studies, sodium dextran sulfate and trinitrobenzene sulfonic acid were used to induce colitis. Eleven probiotic species have been genetically modified to produce therapeutic substances, including IL-10, antimicrobial peptides, antioxidant enzymes, and short-chain fatty acids, with potential therapeutic properties against colitis. The results showed generally positive effects of gm probiotics in reducing disease activity and ameliorating intestinal damage in IBD models; however, the efficacy of gm probiotics compared to that of wild-type probiotics in many studies was unclear. The main mechanisms identified include modulation of the diversity and composition of the gut microbiota, production of regulatory metabolites by beneficial bacteria, reduction of the pro- to anti-inflammatory cytokine ratio in colonic tissue and plasma, modulation of oxidative stress activity in the colon, and improvement of intestinal barrier integrity. Moreover, only one clinical trial with 10 patients with Crohn's disease was included, which showed that L. lactis producing IL-10 was safe, and a decrease in disease activity was observed in these patients.ConclusionsGm probiotics have a certain efficacy in colitis models through several mechanisms. However, given the scarcity of clinical trials, it is important for researchers to pay more attention to gm probiotics that are more effective and safer than wild-type probiotics to facilitate further clinical translation.

Dataset Information

Genetically engineered probiotics as catalytic glucose depriver for tumor starvation therapy.

Publications

Genetically engineered probiotics as catalytic glucose depriver for tumor starvation therapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets