Anti-genotoxic and anti-mutagenic activity of Escherichia coli Nissle 1917 as assessed by in vitro tests

2019 ◽  
Vol 10 (4) ◽  
pp. 449-461 ◽  
Author(s):  
D. Janosch ◽  
S. Dubbert ◽  
K. Eiteljörge ◽  
B.W.K. Diehl ◽  
U. Sonnenborn ◽  
...  

Anti-genotoxic or anti-mutagenic activity has been described for a number of Gram-positive probiotic bacterial species. Here we present evidence that Gram-negative Escherichia coli Nissle 1917 (EcN) also displays anti-genotoxic/anti-mutagenic activity, as assessed in vitro by the Comet Assay and the Ames Test, respectively. This activity was demonstrated by use of the mutagens 4-nitroquinoline-1-oxide (NQO), hydrogen peroxide (H2O2) and benzo(a) pyrene (B[a]P). For both assays and all three test agents the anti-genotoxic/anti-mutagenic activity of EcN was shown to be concentration dependent. By the use of extracts of bacteria that were inactivated by various procedures (heat treatment, ultrasound sonication or ultraviolet light irradiation), mechanistic explanations could be put forward. The proposed mechanisms were enforced by treating the bacterial material with proteinase K prior to testing. The mutagen H2O2 is most likely inactivated by enzymic activity, with catalase a likely candidate, while several explanations can be put forward for inactivation of B[a]P. NQO is most likely inactivated by metabolising enzymes, since the formation of the metabolite 4-aminoquinoline could be demonstrated. In conclusion, the in vitro results presented here make a strong case for antimutagenic properties of EcN.

2020 ◽  
Author(s):  
Binghua Lu ◽  
Huijun Yang ◽  
Fei Liu ◽  
Yunjun Sun ◽  
Haocheng He ◽  
...  

Abstract Escherichia coli Nissle 1917 (EcN) is a non-pathogenic probiotic. Previous studies have indicated that EcN can accumulate and proliferate selectively in solid tumours in BALB/c mouse models. In this study, EcN was engineered to express human interleukin 2 (hIL-2), which is known to enhance immune responses to tumours by activating a variety of immune cells. IL-2 expressed by EcN was proven to activate PBMCs in vitro. Compared to control EcN, intraperitoneally injected EcN expressing hIL-2 (EcN(hIL-2)) was selectively distributed in the tumour microenvironment and inhibited the growth of CT26 tumours in a tumour-bearing mouse model. Antitumour activity was achieved without toxicity to key normal organs and tissues, such as liver, spleen and kidneys. The antitumour mechanism was associated with the infiltration of inflammatory cells, such as T cells, neutrophils and macrophages. These findings provide evidence that the combination of tumour-targeting EcN bacteria and delivery of the immunostimulatory factor IL-2 can be exploited as a promising tumour immunotherapy.


2011 ◽  
Vol 186 (4S) ◽  
pp. 1678-1683 ◽  
Author(s):  
Douglas W. Storm ◽  
Stephen A. Koff ◽  
Dennis J. Horvath ◽  
Birong Li ◽  
Sheryl S. Justice

2020 ◽  
Author(s):  
Binghua Lu ◽  
Huijun Yang ◽  
Fei Liu ◽  
Yunjun Sun ◽  
Haocheng He ◽  
...  

Abstract Escherichia coli Nissle 1917 (EcN) is non-pathogenic probiotic bacteria. Previous studies have indicated that EcN can accumulate and proliferate selectively in solid tumours in BALB/c mouse models. In this study, EcN was engineered to express human interleukin 2 (hIL-2), which is known to enhance immune responses to tumours by activating a variety of immune cells. IL-2 expressed by EcN was proven to activate PBMCs in vitro. Compared to control EcN, intraperitoneally injected EcN expressing hIL-2 (EcN(hIL-2)) was selectively distributed in the tumour microenvironment and inhibited the growth of CT26 tumours in a tumour-bearing mouse model. Antitumour activity was achieved without toxicity to key normal organs and tissues, such as liver, spleen and kidneys. The antitumour mechanism was associated with the infiltration of inflammatory cells, such as T cells, neutrophils and macrophages. These findings provide evidence that the combination of tumour-targeting EcN bacteria and delivery of the immunostimulatory factor IL-2 can be exploited as a promising tumour immunotherapy.


2020 ◽  
Author(s):  
Binghua Lu ◽  
Huijun Yang ◽  
Fei Liu ◽  
Yunjun Sun ◽  
Haocheng He ◽  
...  

Abstract Escherichia coli Nissle 1917 (EcN) is non-pathogenic probiotic bacteria. Previous studies have indicated that EcN can accumulate and proliferate selectively in solid tumours in BALB/c mouse models. In this study, EcN was engineered to express human interleukin 2 (hIL-2), which is known to enhance immune responses to tumours by activating a variety of immune cells. IL-2 expressed by EcN was proven to activate PBMCs in vitro. Compared to control EcN, intraperitoneally injected EcN expressing hIL-2 (EcN(hIL-2)) was selectively distributed in the tumour microenvironment and inhibited the growth of CT26 tumours in a tumour-bearing mouse model. Antitumour activity was achieved without toxicity to key normal organs and tissues, such as liver, spleen and kidneys. The antitumour mechanism was associated with the infiltration of inflammatory cells, such as T cells, neutrophils and macrophages. These findings provide evidence that the combination of tumour-targeting EcN bacteria and delivery of the immunostimulatory factor IL-2 can be exploited as a promising tumour immunotherapy.


mSphere ◽  
2021 ◽  
Author(s):  
Jean-Philippe Nougayrède ◽  
Camille V. Chagneau ◽  
Jean-Paul Motta ◽  
Nadège Bossuet-Greif ◽  
Marcy Belloy ◽  
...  

Nissle 1917 is sold as a probiotic and considered safe even though it has been known since 2006 that it harbors the genes for colibactin synthesis. Colibactin is a potent genotoxin that is now linked to causative mutations found in human colorectal cancer.


2020 ◽  
Author(s):  
Binghua Lu ◽  
Huijun Yang ◽  
Fei Liu ◽  
Yunjun Sun ◽  
Haocheng He ◽  
...  

Abstract Escherichia coli Nissle 1917 (EcN) is non-pathogenic probiotic bacteria. Previous studies have indicated that EcN can accumulate and proliferate selectively in solid tumours in BALB/c mouse models. In this study, EcN was engineered to express human interleukin 2 (hIL-2), which is known to enhance immune responses to tumours by activating a variety of immune cells. IL-2 expressed by EcN was proven to activate PBMCs in vitro. Compared to control EcN, intraperitoneally injected EcN expressing hIL-2 (EcN(hIL-2)) was selectively distributed in the tumour microenvironment and inhibited the growth of CT26 tumours in a tumour-bearing mouse model. Antitumour activity was achieved without toxicity to key normal organs and tissues, such as liver, spleen and kidneys. The antitumour mechanism was associated with the infiltration of inflammatory cells, such as T cells, neutrophils and macrophages. These findings provide evidence that the combination of tumour-targeting EcN bacteria and delivery of the immunostimulatory factor IL-2 can be exploited as a promising tumour immunotherapy.


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