Ready, aim, fire! E.coli reprogrammed to target biofilms

Researchers reprogrammed the bacterium to specifically recognize, migrate toward, and eradicate both dispersed and biofilm-encased pathogenic Pseudomonas aeruginosa cells.

Pseudomonas aeruginosa is an environmental bacterium which can be found in food such as vegetables and drinking water, according to the Drinking Water Research Foundation (DWRF).

Matthew Wook Chang et al explained that biofilm infections are difficult to treat because the bacteria hide away under a protective barrier of sugars, DNA and proteins which makes them very resistant to conventional therapies.

Pathogen-seeking E.coli​

They reprogrammed E. coli, which also comes in harmless varieties, to sense Pseudomonas aeruginosa and swim directly towards it and launch an attack with an antimicrobial peptide and an enzyme that breaks down biofilms.

The reprogrammed E. coli degraded the mature biofilm matrix and killed the latent cells by expressing and secreting the antimicrobial peptide microcin S and the nuclease DNaseI upon detection of quorum sensing (QS) molecules naturally secreted by P. aeruginosa.

Engineering of bacterial cells has been gaining interest but limitations include effective antimicrobial activities being dependant on the molecular diffusion of produced therapeutic compounds towards the target pathogen, explained the study.

Biofilm toughness​

Biofilms are hard to remove pathogens that get stuck on machinery and other surfaces in food manufacturing plants.

They form a tough surface skin that resist conventional commercial washing and sanitizing methods and become sources of contamination, resulting in lowered shelf-life of products and potential consumer illness.

Funding came from the National Medical Research Council of Singapore and the US Defense Threat Reduction Agency.

The autonomous ‘Seek and Kill’ system can be applied to other pathogens with sensing of particular signaling molecules, to utilize target-dependent localization to deploy not only toxins but also other enzymes, concluded the study.

Source: ACS Synthetic Biology

Online ahead of print, doi: 10.1021/sb400077j​

“Reprogramming Microbes to Be Pathogen-Seeking Killers​”

Authors: In Young Hwang, Mui Hua Tan, Elvin Koh, Chun Loong Ho, Chueh Loo Poh and Matthew Wook Chang