CONICET | Buscador de Institutos y Recursos Humanos

Biosynthesis and secretion of a complex extracellular matrix (EM) is a hallmark of Salmonella biofilm formation, impacting on its relationship with both the environment and the host. Cellulose is a major component of Salmonella EM and it is considered an antivirulence factor because it interferes with Salmonella proliferation inside macrophages. Its synthesis is stimulated by CsgD, the master regulator of biofilm formation in enterobacteria, which in turn is under the control of MlrA, a MerR-like transcription factor. We identified MlrB, a SPI-2-encoded Salmonella-specific transcription factor homolog to MlrA, that repress transcription of its downstream gene, orf319, and of csgD inside host cells. MlrB is induced in the intracellular environment as well as in a laboratory media mimicking intracellular conditions. In fact, a Salmonella ΔmlrB strain is attenuated in virulence and exhibited high levels of csgD expression compared with the wild type strain. However, the inactivation of either csgD or the CsgD-controlled cellulose synthase-coding gene in this mutant strain restored intramacrophage proliferation to rates comparable to wild-type bacteria. These data indicate that MlrB-directed repression of CsgD inside host cells decreased cellulose synthase activation and production of this EM component. On the other hand, we noticed that although expression of MlrB follows that of T3SS-2 genes, deletion of ssrB, the master regulator of the secretion system-coding genes, had no effect on mlrB transcription. By contrast, MlrB expression requires the activation of PhoP and PmrA, the response regulators of two key regulatory systems required for intracellular survival. Our findings provide a novel link between biofilm formation and Salmonella virulence.