Biofilm Bacteria Use Stress Responses to Detect and Respond to Competitors

• Published in: Current biology 2020-04, Vol.30 (7), p.1231-1244.e4
• Main Authors: Lories, Bram, Roberfroid, Stefanie, Dieltjens, Lise, De Coster, David, Foster, Kevin R., Steenackers, Hans P.
• Format: Article
• Language: English
• Subjects: antibiotic tolerance; biofilm; competition; competition sensing; epithelial invasion; microbial ecology; Salmonella; stress response systems
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2020.01.065

Bacteria use complex regulatory networks to cope with stress, but the function of these networks in natural habitats is poorly understood. The competition sensing hypothesis states that bacterial stress response systems can serve to detect ecological competition, but studying regulatory responses in diverse communities is challenging. Here, we solve this problem by using differential fluorescence induction to screen the Salmonella Typhimurium genome for loci that respond, at the single-cell level, to life in biofilms with competing strains of S. Typhimurium and Escherichia coli. This screening reveals the presence of competing strains drives up the expression of genes associated with biofilm matrix production (CsgD pathway), epithelial invasion (SPI1 invasion system), and, finally, chemical efflux and antibiotic tolerance (TolC efflux pump and AadA aminoglycoside 3-adenyltransferase). We validate that these regulatory changes result in the predicted phenotypic changes in biofilm, mammalian cell invasion, and antibiotic tolerance. We further show that these responses arise via activation of major stress responses, providing direct support for the competition sensing hypothesis. Moreover, inactivation of the type VI secretion system (T6SS) of a competitor annuls the responses to competition, indicating that T6SS-derived cell damage activates these stress response systems. Our work shows that bacteria use stress responses to detect and respond to competition in a manner important for major phenotypes, including biofilm formation, virulence, and antibiotic tolerance. •Salmonella induces biofilm formation, invasion, and efflux in response to competition•Traditional stress response systems regulate this competitive response•These stress responses are activated in response to a T6SS-mediated attack•Together, these data provide direct support for the competition sensing hypothesis Bacteria typically live in dense and diverse communities; however, little is known about how bacteria respond to competing strains on a molecular level. Lories et al. report that Salmonella detects competitors via stress response systems and induces pathways important for biofilm formation, epithelial invasion, and antibiotic tolerance.