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Bacterial Anti-Phage Defence Systems
Yeda R&D Co. Ltd Israel flag Israel
Abstract ID: 1690
Optimal growth and metabolic activities of Lactic Acid Bacterial (LAB) starters are critical for assuring high-quality fermentation in the manufacturing process of numerous dairy products. Despite extensive efforts,...
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Introduction/Background

Optimal growth and metabolic activities of Lactic Acid Bacterial (LAB) starters are critical for assuring high-quality fermentation in the manufacturing process of numerous dairy products. Despite extensive efforts, phage infection of starter cultures for dairy processing remains the most common cause of slow or incomplete fermentation and product downgrading. Standard anti-phage measures (sanitation, culture handling) fail to provide sufficient protection, exposing the production process to massive economic setbacks.
Extensive R&D efforts have led to the discovery of phage resistance systems, however many phages can circumvent these systems, and in addition not all LABs can accommodate them.

Aims/Hypothesis

Therefore, there is a strong need for additional defence systems that could naturally protect LABs against phages.

Results

Toxin/antitoxin (TA) modules, composed of a toxic protein and a counteracting antitoxin, are proposed to function in phage defence via abortive infection. The two genes, which reside on the same operon, code for small proteins where inhibition of the toxin is carried out through protein-protein interaction. Upon a specific signal (phage infection) the antitoxin degrades rapidly by one of the housekeeping bacterial proteases, resulting in either bacteriocidic (cell-killing) or bacteriostatic (growth-inhibiting) effects, thus protecting the colony against phage spread. The inventors took advantage of the concept that toxins could only be cloned when the neighbouring antitoxin was present on the same clone to systematically reveal active TA pairs. Following extensive statistical and experimental validations, 8 novel families of TA pairs that are likely to play a role in phage defence were identified. By introducing these systems into new bacteria, the inventors showed that the toxin/antitoxin pairs could protect the engineered bacteria from phage infection.
BREX is a novel cassette of six genes that confers protection against a wide range of phages, including virulent and temperate ones. This cassette is composed of genes not typically found in other defence systems, and hence employs a novel mechanism of anti-phage protection. Scientists at the Sorek lab further uncovered the mode of action of this novel system. It was shown that the system is not an abortive infection system (i.e., does not lead to suicide of the infected cell), and that it allows phage adsorption but blocks phage replication in a DNA degradation independent manner.

Conclusion

The Sorek laboratory at the Weizmann Institute of Science has recently identified hundreds of novel functional toxin/antitoxin systems in bacterial genomes. These systems were discovered using analysis of data from millions of shotgun cloning experiments across 388 bacterial species. Acting as an abortive infection agent to prevent phage spread, some of these systems were already validated as conferring resistance against phage infection upon introduction to E.coli cells. In another novel technology, researchers at Dr. Rotem Sorek's lab identified a novel anti phage gene cassette, termed BREX (Bacteriophage Exclusion), which confers complete or partial resistance against phages spanning a wide phylogeny of phage types, including lytic and temperate ones.

Relevance/Opportunity

Tools for conferring anti-phage traits to bacterial starters. Please enquire quoting reference no. 1690 regarding licensing or codevelopment partnerships.
FEATURED
Last Updated May 2015
Technology Type PLATFORM
Phase of Development CLINICAL TRIALS
CORPORATION