Salmonella expresses foreign genes during infection by degrading their silencer.
Jeongjoon ChoiEduardo A GroismanPublished in: Proceedings of the National Academy of Sciences of the United States of America (2020)
The heat-stable nucleoid structuring (H-NS, also referred to as histone-like nucleoid structuring) protein silences transcription of foreign genes in a variety of Gram-negative bacterial species. To take advantage of the products encoded in foreign genes, bacteria must overcome the silencing effects of H-NS. Because H-NS amounts are believed to remain constant, overcoming gene silencing has largely been ascribed to proteins that outcompete H-NS for binding to AT-rich foreign DNA. However, we report here that the facultative intracellular pathogen Salmonella enterica serovar Typhimurium decreases H-NS amounts 16-fold when inside macrophages. This decrease requires both the protease Lon and the DNA-binding virulence regulator PhoP. The decrease in H-NS abundance reduces H-NS binding to foreign DNA, allowing transcription of foreign genes, including those required for intramacrophage survival. The purified Lon protease degraded free H-NS but not DNA-bound H-NS. By displacing H-NS from DNA, the PhoP protein promoted H-NS proteolysis, thereby de-repressing foreign genes-even those whose regulatory sequences are not bound by PhoP. The uncovered mechanism enables a pathogen to express foreign virulence genes during infection without the need to evolve binding sites for antisilencing proteins at each foreign gene.
Keyphrases
- dengue virus
- genome wide
- genome wide identification
- zika virus
- transcription factor
- escherichia coli
- circulating tumor
- bioinformatics analysis
- gram negative
- dna binding
- multidrug resistant
- cell free
- pseudomonas aeruginosa
- staphylococcus aureus
- single molecule
- dna methylation
- genome wide analysis
- biofilm formation
- cystic fibrosis
- copy number
- protein protein
- small molecule
- reactive oxygen species
- binding protein
- nucleic acid
- circulating tumor cells
- antibiotic resistance genes