Nucleoid-associated proteins shape the global protein occupancy and transcriptional landscape of a clinical isolate ofVibrio cholerae

Abstract

Vibrio cholerae, the causative agent of the diarrheal disease cholera, poses an ongoing health threat due to its wide repertoire of horizontally acquired elements (HAEs) and virulence factors. New clinical isolates of the bacterium with improved fitness abilities, often associated with HAEs, frequently emerge. The appropriate control and expression of such genetic elements is critical for the bacteria to thrive in the different environmental niches it occupies. H-NS, the histone-like nucleoid structuring protein, is the best studied xenogeneic silencer of HAEs in gamma-proteobacteria. Although H-NS and other highly abundant nucleoid-associated proteins (NAPs) have been shown to play important roles in regulating HAEs and virulence in model bacteria, we still lack a comprehensive understanding of how different NAPs modulate transcription in V. cholerae. By obtaining genome-wide measurements of protein occupancy and active transcription in a clinical isolate of V. cholerae, harboring recently discovered HAEs encoding for phage defense systems, we show that a lack of H-NS causes a robust increase in the expression of genes found in many HAEs. We further found that TsrA, a protein with partial homology to H-NS, regulates virulence genes primarily through modulation of H-NS activity. We also identified a few sites that are affected by TsrA independently of H-NS, suggesting TsrA may act with diverse regulatory mechanisms. Our results demonstrate how the combinatorial activity of NAPs is employed by a clinical isolate of an important pathogen to regulate recently discovered HAEs.

Multiscale regulation of nutrient stress responses in Escherichia coli from chromatin structure to small regulatory RNAs

“…Globally, nucleoid-associated proteins can bind long segments of the genome to bend and compact the DNA in response to changing environments (8). Like eukaryotic heterochromatin, these elongated protein occupancy domains, referred to as EPODs (9), can condense long sections of the DNA and silence transcription by blocking the accessibility of RNAP to internal promoters (10)(11)(12)(13) or aiding in RNAP stalling and backtracking (14,15). Nucleoid-associated proteins often respond to growth and nutrient variability, typified in E. coli by proteins such as the amino acid regulator Lrp (6), and the growth phase dependent HU and Dps (16).…”