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Construction of protective probiotics for precise prevention and control of drug-resistant biofilm

Abstract

Bacterial biofilm is an environmental adaptation structure formed by microorganisms. After reaching maturity biofilms, intestinal pathogens will develop resistance to antibiotics and host immunity, elicit infection repeatedly, and induce diarrhea or inflammation of the gastrointestinal tract. In mature biofilms, the network structure formed by eDNA is crucial for the maintenance of biofilm stability. The objective of this endeavor was to modify Nissle 1917 so that it could identify Pseudomonas aeruginosa, stimulate the production of recombinant HMGB1 protein and PslG polysaccharide enzyme, degrade the compact structure established by eDNA, and eradicate resistance to biofilm. The use of these engineered bacteria in the prevention and treatment of diseases brought on by enteropathogenic biofilm infections is possible.

Our aim and story

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In an impressive microbiology class, we learned about biofilm. It is known to be formed by bacteria and extracellular polymers (eDNA, proteins and polysaccharides). Mature biofilm forms a dense network that envelopes the bacterial surface and blocks the entry of antibiotics, resulting in highly resistant bacterial colonies.

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Pseudomonas aeruginosa, as a well-known opportunistic pathogen, can attach to the human gut through biofilm and infect patients when they are frail. Therefore, we decided to develop a novel approach to achieve efficient and precise removal of P. aeruginosa biofilm.

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After a thorough reading of the literature, a lot of group discussions, and an exchange of views with the teacher, we had a preliminary idea.

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We engineered E. coli Nissle 1917 (EcN), a probiotic that can colonize the human body, to sense the presence of Pseudomonas aeruginosa around it and release target proteins HMGB1 and PslG to achieve precise clearance of P. aeruginosa biofilm. Thus, removing Pseudomonas aeruginosa that adheres to the gut.

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This is the beginning of our SUSTech-CHINA story.