Food-Grade Bacteria Combat Pathogens by Blocking AHL-Mediated Quorum Sensing and Biofilm Formation
Kirsi Savijoki, Paola San-Martin-Galindo, Katriina Pitkänen, Minnamari Edelmann, Annika Sillanpää, Cim van der Velde, Ilkka Miettinen, Jayendra Z. Patel, Jari Yli‐Kauhaluoma, Mataleena Parikka, Adyary Fallarero, Pekka Varmanen
Abstract
Disrupting bacterial quorum sensing (QS) signaling is a promising strategy to combat pathogenic biofilms without the development of antibiotic resistance. Here, we report that food-associated bacteria can interfere with the biofilm formation of a Gram-negative pathogenic bacterium by targeting its AHL (acyl-homoserine lactone) QS system. This was demonstrated by screening metabolic end-products of different lactobacilli and propionibacteria using Gram-negative and biofilm-forming Chromobacterium violaceum as the QS reporter and our anti-QS microscale screening platform with necessary modifications. The method was optimized in terms of the inoculation technique and the concentrations of D-glucose and L-tryptophan, two key factors controlling the synthesis of violacein, a purple pigment indicating the activation of the QS system in C. violaceum. These improvements resulted in ca. 16-times higher violacein yields and enabled revealing anti-QS effects of Lactobacillus acidophilus, Lentilactobacillus kefiri, Lacticaseibacillus rhamnosus and Propionibacterium freudenreichii, including new cheese-associated strains. Our findings also suggest that acetate and propionate excreted by these species are the main factors that interrupt the QS-mediated signaling and subsequent biofilm growth without affecting the cell viability of the C. violaceum reporter. Thus, the present study reports a revised anti-QS screening method to accurately define new bacteria with an ability to combat pathogens in a safe and sustainable way.