Balance between bacterial extracellular matrix production and intramacrophage proliferation by a Salmonella‐specific SPI‐2‐encoded transcription factor

• Published in: Molecular microbiology 2021-10, Vol.116 (4), p.1022-1032
• Main Authors: Echarren, María Laura, Figueroa, Nicolás R., Vitor‐Horen, Luisina, Pucciarelli, M. Graciela, García‐del Portillo, Francisco, Soncini, Fernando C.
• Format: Article
• Language: English
• Subjects: Animals; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biofilms; Biosynthesis; Cellulose; Cellulose - metabolism; Cellulose synthase; cellulose‐production; CsgD; Extracellular matrix; Extracellular Matrix - metabolism; Gene Expression Regulation, Bacterial; Homology; Host Microbial Interactions; Inactivation; macrophage survival; Macrophages; Macrophages - microbiology; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mimicry; MlrA‐homologue; RAW 264.7 Cells; Salmonella; Salmonella Infections - microbiology; Salmonella typhimurium - genetics; Salmonella typhimurium - metabolism; Salmonella typhimurium - pathogenicity; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription factors; Transcription, Genetic; Virulence; Virulence factors; Virulence Factors - metabolism
• ISSN: 0950-382X; 1365-2958
• DOI: 10.1111/mmi.14789

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. It is considered an anti‐virulence factor because it interferes with Salmonella proliferation inside macrophages and virulence in mice. 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. In this work, we identified a SPI‐2‐encoded Salmonella‐specific transcription factor homolog to MlrA, MlrB, that represses transcription of its downstream gene, orf319, and of csgD inside host cells. MlrB is induced in laboratory media mimicking intracellular conditions and inside macrophages, and it is required for intramacrophage proliferation. An increased csgD expression is observed in the absence of MlrB inside host cells. Interestingly, inactivation of the CsgD‐controlled cellulose synthase‐coding gene restored intramacrophage proliferation to rates comparable to wild‐type bacteria in the absence of MlrB. These data indicate that MlrB represses CsgD expression inside host cells and suggest that this repression lowers the activation of the cellulose synthase. Our findings provide a novel link between biofilm formation and Salmonella virulence. Salmonella biofilm extracellular matrix, particularly one of its components, cellulose, interferes with Salmonella survival inside macrophages and virulence in mice. Its synthesis is controlled by the major extracellular matrix regulator, CsgD, which in turn is under MlrA regulation. In this work, A Salmonella‐specific MlrA‐like transcription factor, MlrB, is characterized. MlrB is required for macrophages proliferation. It interferes with CsgD expression inside host cells and synthesis of the extracellular matrix.