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Bioengineered Escherichia coli Nissle 1917 for tumour-targeting therapy.

ABSTRACT: Bacterial vectors, as microscopic living 'robotic factories', can be reprogrammed into microscopic living 'robotic factories', using a top-down bioengineering approach to produce and deliver anticancer agents. Most of the current research has focused on bacterial species such as Salmonella typhimurium or Clostridium novyi. However, Escherichia coli Nissle 1917 (EcN) is another promising candidate with probiotic properties. EcN offers increased applicability for cancer treatment with the development of new molecular biology and complete genome sequencing techniques. In this review, we discuss the genetics and physical properties of EcN. We also summarize and analyse recent studies regarding tumour therapy mediated by EcN. Many challenges remain in the development of more promising strategies for combatting cancer with EcN.

SUBMITTER: Yu X

PROVIDER: S-EPMC7111071 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Bioengineered Escherichia coli Nissle 1917 for tumour-targeting therapy.

Yu Xiaoli X Lin Changsen C Yu Jing J Qi Qingsheng Q Wang Qian Q

Microbial biotechnology 20191221 3

Bacterial vectors, as microscopic living 'robotic factories', can be reprogrammed into microscopic living 'robotic factories', using a top-down bioengineering approach to produce and deliver anticancer agents. Most of the current research has focused on bacterial species such as Salmonella typhimurium or Clostridium novyi. However, Escherichia coli Nissle 1917 (EcN) is another promising candidate with probiotic properties. EcN offers increased applicability for cancer treatment with the developm ...[more]

PMID: 31863567

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Emerging strategies for engineering Escherichia coli Nissle 1917-based therapeutics.

Project description:Engineered microbes are rapidly being developed for the delivery of therapeutic modalities to sites of disease. Escherichia coli Nissle 1917 (EcN), a genetically tractable probiotic with a well-established human safety record, is emerging as a favored chassis. Here, we summarize the latest progress in rationally engineered variants of EcN for the treatment of infectious diseases, metabolic disorders, and inflammatory bowel diseases (IBDs) when administered orally, as well as cancers when injected directly into tumors or the systemic circulation. We also discuss emerging studies that raise potential safety concerns regarding these EcN-based strains as therapeutics due to their secretion of a genotoxic colibactin that can promote the formation of DNA double-stranded breaks in mammalian DNA.

| S-EPMC9378478 | biostudies-literature

RNA sequencing of Escherichia coli Nissle 1917 after HOCl stress

Project description:RNA sequencing of Escherichia coli Nissle 1917 before and after HOCl treatment was perfomed to identify pathways that may be important in responding to oxidative stress caused by reachive chlorine species (RCS).

2020-01-23 | GSE144068 | GEO

The Probiotic Escherichia coli Strain Nissle 1917 Combats Lambdoid Bacteriophages stx and ?.

Project description:Shiga toxin (Stx) producing E. coli (STEC) such as Enterohemorrhagic E. coli (EHEC) are the major cause of foodborne illness in humans. In vitro studies showed the probiotic Escherichia coli strain Nissle 1917 (EcN) to efficiently inhibit the production of Stx. Life threatening EHEC strains as for example the serotype O104:H4, responsible for the great outbreak in 2011 in Germany, evolutionary developed from certain E. coli strains which got infected by stx2-encoding lambdoid phages turning the E. coli into lysogenic and subsequently Stx producing strains. Since antibiotics induce stx genes and Stx production, EHEC infected persons are not recommended to be treated with antibiotics. Therefore, EcN might be an alternative medication. However, because even commensal E. coli strains might be converted into Stx-producers after becoming host to a stx encoding prophage, we tested EcN for stx-phage genome integration. Our experiments revealed the resistance of EcN toward not only stx-phages but also against lambda-phages. This resistance was not based on the lack of or by mutated phage receptors. Rather it involved the expression of a phage repressor (pr) gene of a defective prophage in EcN which was able to partially protect E. coli K-12 strain MG1655 against stx and lambda phage infection. Furthermore, we observed EcN to inactivate phages and thereby to protect E. coli K-12 strains against infection by stx- as well as lambda-phages. Inactivation of lambda-phages was due to binding of lambda-phages to LamB of EcN whereas inactivation of stx-phages was caused by a thermostable protein of EcN. These properties together with its ability to inhibit Stx production make EcN a good candidate for the prevention of illness caused by EHEC and probably for the treatment of already infected people.

| S-EPMC5987069 | biostudies-literature

Draft Genome Sequence of Escherichia coli Strain Nissle 1917 (Serovar O6:K5:H1).

Project description:We announce the availability of the 5.023-Mbp high-quality draft assembly of the Escherichia coli strain Nissle 1917 (serovar O6:K5:H1) genome. Short genomic segments from this important probiotic strain have been available in public databases, but the full genome sequence has remained inaccessible. Thus, high-coverage, whole genome sequencing of E. coli Nissle 1917 is presented herein. Reannotation and metabolic reconstruction will enable comparative genomics analysis and model-guided predictions of genetic manipulations leading to increased production of the K5 capsular polysaccharide known as N-acetyl heparosan, a precursor to the anticoagulant pharmaceutical heparin.

| S-EPMC3593317 | biostudies-literature

Transcriptional Profiling of the Probiotic Escherichia coli Nissle 1917 Strain under Simulated Microgravity.

Project description:Long-term space missions affect the gut microbiome of astronauts, especially the viability of some pathogens. Probiotics may be an effective solution for the management of gut microbiomes, but there is a lack of studies regarding the physiology of probiotics in microgravity. Here, we investigated the effects of microgravity on the probiotic Escherichia coli Nissle 1917 (EcN) by comparing transcriptomic data during exponential and stationary growth phases under simulated microgravity and normal gravity. Microgravity conditions affected several physiological features of EcN, including its growth profile, biofilm formation, stress responses, metal ion transport/utilization, and response to carbon starvation. We found that some changes, such as decreased adhesion ability and acid resistance, may be disadvantageous to EcN relative to gut pathogens under microgravity, indicating the need to develop probiotics optimized for space flight.

| S-EPMC7215827 | biostudies-literature

Escherichia coli Nissle 1917

Project description:Escherichia coli Nissle 1917 proteome

| PRJNA71129 | ENA

Escherichia coli Nissle 1917

Project description:Escherichia coli Nissle 1917 Genome sequencing

| PRJNA248167 | ENA

Escherichia coli Nissle 1917

Project description:Draft Genome Sequence of Escherichia coli Strain Nissle 1917 (serovar O6:K5:H1)

| PRJEB1192 | ENA

Escherichia coli Nissle 1917

Project description:Escherichia coli Nissle 1917 Genome sequencing

| PRJNA447975 | ENA

Functional investigation of the chromosomal ccdAB and hipAB operon in Escherichia coli Nissle 1917.

Project description:Toxin-antitoxin systems (TASs) have attracted much attention due to their important physiological functions. These small genetic factors have been widely studied mostly in commensal Escherichia coli strains, whereas the role of TASs in the probiotic E. coli Nissle 1917 (EcN) is still elusive. Here, the physiological role of chromosomally encoded type II TASs in EcN was examined. We showed that gene pair ECOLIN_00240-ECOLIN_00245 and ECOLIN_08365-ECOLIN_08370 were two functional TASs encoding CcdAB and HipAB, respectively. The homologs of CcdAB and HipAB were more conserved in E. coli species belonging to pathogenic groups, suggesting their important roles in EcN. CRISPRi-mediated repression of ccdAB and hipAB significantly reduced the biofilm formation of EcN in the stationary phase. Moreover, ccdAB and hipAB were shown to be responsible for the persister formation in EcN. Biofilm and persister formation of EcN controlled by the ccdAB and hipAB were associated with the expression of genes involved in DNA synthesis, SOS response, and stringent response. Besides, CRISPRi was proposed to be an efficient tool in annotating multiple TASs simultaneously. Collectively, our results advance knowledge and understanding of the role of TASs in EcN, which will enhance the utility of EcN in probiotic therapy.Key points• Two TASs in EcN were identified as hipAB and ccdAB.• Knockdown of HipAB and CcdAB resulted in decreased biofilm formation of EcN.• Transcriptional silencing of hipAB and ccdAB affected the persister formation of EcN.• An attractive link between TASs and stress response was unraveled in EcN.• CRISPRi afforded a fast and in situ annotation of multiple TASs simultaneously.

| S-EPMC7293176 | biostudies-literature

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