Metabolic Activation of CsgD in the Regulation of Salmonella Biofilms

Abstract

Among human food-borne pathogens, gastroenteritis-causing <i>Salmonella</i> strains have the most real-world impact. Like all pathogens, their success relies on efficient transmission. Biofilm formation, a specialized physiology characterized by multicellular aggregation and persistence, is proposed to play an important role in the <i>Salmonella</i> transmission cycle. In this manuscript, we used luciferase reporters to examine the expression of <i>csgD</i>, which encodes the master biofilm regulator. We observed that the CsgD-regulated biofilm system responds differently to regulatory inputs once it is activated. Notably, the CsgD system became unresponsive to repression by Cpx and H-NS in high osmolarity conditions and less responsive to the addition of amino acids. Temperature-mediated regulation of <i>csgD</i> on agar was altered by intracellular levels of RpoS and cyclic-di-GMP. In contrast, the addition of glucose repressed CsgD biofilms seemingly independent of other signals. Understanding the fine-tuned regulation of <i>csgD</i> can help us to piece together how regulation occurs in natural environments, knowing that all <i>Salmonella</i> strains face strong selection pressures both within and outside their hosts. Ultimately, we can use this information to better control <i>Salmonella</i> and develop strategies to break the transmission cycle.