The intramacrophage extracellular matrix modulator MlrB is under PhoP/PhoQ and PmrA/PmrB transcriptional control Salmonella Biology and Pathogenesis.

CISANA P; FOLMER MP; ECHARREN ML; CHECA SK; SONCINI FC

Lucca (Barga), Italia

Congreso; Salmonella Biology and Pathogenesis. Salmonella: From Basic Biology to Complex Pathogen-Host Interactions; 2023

Gordon Research Conference

Biosynthesis and secretion of a complex extracellular matrix are hallmarks of Salmonella biofilm formation, impacting on its relationship with both the environment and the host. Cellulose is a major component of Salmonella extracellular matrix. 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 recently identified a SPI-2-encoded Salmonella-specific transcription factor homolog to MlrA, MlrB, that represses transcription of csgD inside host cells, lowering the activation of the cellulose synthase and thus allowing Salmonella intramacrophage proliferation. We now show that mlrB transcriptional induction is not under the control of SsrB/SsrA SPI-2 two component system, but depends on PhoP/PhoQ and PmrA/PmrB. We also show that the PhoP/PhoQ control over mlrB transcription is exerted through the PmrA/PmrB system. Furthermore, we identified a PmrA-binding site at the mlrB promoter that is responsible for this regulation. We propose that PhoPQ/PmrAB-directed activation allows the expression of the MerR-like regulator inside the host cells, counteracting MlrA induction of extracellular matrix production and enabling Salmonella intracellular proliferation.