Engineered lactobacilli display anti-biofilm and growth suppressing activities againstPseudomonas aeruginosa

Biofilms are an emerging target for new therapeutics in the effort to address the continued increase in resistance and tolerance to traditional antimicrobials. In particular, the distinct nature of the biofilm growth state often means that traditional antimicrobials, developed to combat planktonic cells, are ineffective. Biofilm treatments are designed to both reduce pathogen load at an infection site and decrease the development of resistance by rendering the embedded organisms more susceptible to treatment at lower antimicrobial concentrations. In this work, we developed a new antimicrobial treatment modality by characterizing the natural capacity of two lactobacilli, L. plantarum and L. rhamnosus , to inhibit P. aeruginosa growth, biofilm formation, and biofilm viability. We further engineered these lactic acid bacteria (LAB) to secrete enzymes known to degrade P. aeruginosa biofilms and show that our best performing engineered LAB, secreting a pathogen-derived enzyme (PelA hyd ), degrades up to 85 % of P. aeruginosa biofilm.