Combating bacterial infections in an age of increasing resistance to traditional antimicrobial therapies requires the development of new treatments that combat alternative virulence factors of pathogenic bacteria. Bacterial biofilms – surface-associated microbial communities residing within an extracellular matrix – are an important virulence factor that increase resistance/decrease sensitivity to antibiotics and inhibit the normal healing response. Disrupting the structural elements of the biofilm is a viable strategy for re-sensitization of biofilm associated microbes to antimicrobials, an essential step in noninvasive infection clearance. Recent work on alternative wound treatments has shown that topical application of probiotic lactic acid bacteria (LAB) inhibits pathogenic bacterial growth on wounds and promotes wound healing. LAB are also known to produce a variety of antimicrobials, such as type II bacteriocins produced by Lactobacillus sakei and Lactobacillus plantarum and the antimicrobial metabolite reuterin produced by Lactobacillus reuteri. However, LAB activity against mature biofilms has not been characterized. Furthermore, advances in recombineering of LAB provide the opportunity to enhance their innate antimicrobial and anti-biofilm capacities. In this talk, we will describe the design of a synthetic microconsortium of engineered LAB that serve as a topical wound treatment and provide therapeutic benefit through synergistic combination of various biofilm degrading enzymes. This LAB microconsortium is designed to disassemble mature biofilm matrices and inhibit nascent biofilm formation through enzymatic disruption, while also inhibiting microbial growth through production of antimicrobial compounds. We will discuss our recent efforts in development of this system against Pseudomonas aeruginosa and Staphylococcus aureus – two major opportunistic biofilm-forming pathogens frequently found in chronic wound infection sites.

Targeting biofilm-forming pathogens using a microconsortium of engineered lactic acid bacteria (LAB)

2019 Spring National Meeting

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