Deciphering the interplay between the genotoxic and probiotic activities of Escherichia coli Nissle 1917 Original paper
Researched by:
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Divine Aleru
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Divine Aleru
Read MoreI am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.
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Microbes
Microbes
Microbes, short for microorganisms, are tiny living organisms that are ubiquitous in the environment, including on and inside the human body. They play a crucial role in human health and disease, functioning within complex ecosystems in various parts of the body, such as the skin, mouth, gut, and respiratory tract. The human microbiome, which is […]
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Divine Aleru
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Researched by:
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Divine Aleru
ID
Divine Aleru
Read More
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Divine Aleru
What was studied?
This study focused on the interplay between the genotoxic and probiotic activities of Escherichia coli Nissle 1917 (EcN), a well-established probiotic. Researchers investigated the relationship between EcN’s production of colibactin, a genotoxin, and its beneficial effects, particularly its antagonistic activities against other Enterobacteriaceae. The study aimed to distinguish the genotoxic impact of colibactin from the beneficial antibacterial properties of EcN. The researchers investigated the role of the ClbP protein, which is crucial for colibactin activation, and explored how mutations in this protein could decouple genotoxicity from antibacterial activity. They also examined the synthesis of siderophore-microcins (MccH47 and MccM), which contribute to EcN’s antibacterial activity.
Who was studied?
The study focused on Escherichia coli Nissle 1917 (EcN), its mutant strains, and other relevant pathogenic and probiotic E. coli strains. The research used Salmonella enterica and E. coli strains (such as LF82) to assess EcN’s antagonistic activity. Mouse models were employed to study the effect of EcN on pathogen colonization, explicitly focusing on Salmonella in a streptomycin-treated mouse model. The strains used in the study were genetically modified to produce various mutations in the ClbP protein, responsible for the synthesis of colibactin, to test the effects of these changes on both genotoxicity and antibacterial activity.
Most important findings
The study revealed that the ClbP protein is essential for EcN’s antibacterial activity, particularly its production of siderophore-linked microcins (MccH47 and MccM), which inhibit the growth of competing Enterobacteriaceae. However, the study showed that while ClbP is crucial for the antagonistic activity of EcN, it is not necessary for the genotoxic activity associated with colibactin. The researchers were able to decouple these activities by engineering a mutant strain of EcN (clbP-S95R) that retained its antibacterial properties but lost its genotoxic effects. In vivo experiments demonstrated that this mutant still protected mice against Salmonella infections as effectively as the wild-type EcN, offering a pathway to safely use EcN as a probiotic without the risk of genotoxicity.
Key implications
The findings suggest that Escherichia coli Nissle 1917 has a dual nature, with both beneficial probiotic effects and potential risks due to its genotoxic properties. By identifying the specific role of ClbP in both colibactin synthesis and antibacterial activity, the study opens the door for engineering safer strains of EcN. These strains could provide the therapeutic benefits of EcN without the associated risks of genotoxicity. This could have significant implications for the use of probiotics in clinical settings, particularly for treating gastrointestinal infections or inflammatory conditions, where EcN is commonly used.