Dataset Information

Molecular Basis for Environment Sensing by a Nucleoid-Structuring Bacterial Protein Filament.

ABSTRACT: The histone-like nucleoid structuring (H-NS) protein controls the expression of hundreds of genes in Gram-positive bacteria through its capability to coat and condense DNA. This mechanism requires the formation of superhelical H-NS protein filaments that are sensitive to temperature and salinity, allowing H-NS to act as an environment sensor. We use multiscale modeling and simulations to obtain detailed insights into the mechanism of H-NS filament's sensitivity to environmental changes. Through the simulations of the superhelical H-NS filament, we reveal how different environments induce heterogeneity of H-NS monomers. Further, we observe that transient self-association within the H-NS filament creates temperature-inducible strain and might mildly oppose DNA binding. We also probe different H-NS-DNA complex architectures and show that complexation enhances the stability of both DNA and H-NS superhelices. Overall, our results provide unprecedented molecular insights into the environmental sensing and DNA interactions of a prototypical nucleoid-structuring bacterial protein filament.

SUBMITTER: Zhao X

PROVIDER: S-EPMC9346976 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Molecular Basis for Environment Sensing by a Nucleoid-Structuring Bacterial Protein Filament.

Zhao Xiaochuan X Remington Jacob M JM Schneebeli Severin T ST Arold Stefan T ST Li Jianing J

The journal of physical chemistry letters 20210812 32

The histone-like nucleoid structuring (H-NS) protein controls the expression of hundreds of genes in Gram-positive bacteria through its capability to coat and condense DNA. This mechanism requires the formation of superhelical H-NS protein filaments that are sensitive to temperature and salinity, allowing H-NS to act as an environment sensor. We use multiscale modeling and simulations to obtain detailed insights into the mechanism of H-NS filament's sensitivity to environmental changes. Through ...[more]

PMID: 34382809

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Project description:Burkholderia cepacia complex bacteria comprise opportunistic pathogens causing chronic respiratory infections in cystic fibrosis (CF) patients. These microorganisms produce an exopolysaccharide named cepacian, which is considered a virulence determinant. To find genes implicated in the regulation of cepacian biosynthesis, we characterized an evolved nonmucoid variant (17616nmv) derived from the ancestor, Burkholderia multivorans ATCC 17616, after prolonged stationary phase. Lack of cepacian biosynthesis was correlated with downregulation of the expression of bce genes implicated in its biosynthesis. Furthermore, genome sequencing of the variant identified the transposition of the mobile element IS406 upstream of the coding sequence of an hns-like gene (Bmul_0158) encoding a histone-like nucleoid structuring (H-NS) protein, a known global transcriptional repressor. This insertion sequence (IS) element upregulated the expression of Bmul_0158 by 4-fold. Transcriptome analysis identified the global effects of this mutation on gene expression, with major changes in genes implicated in motility, pilus synthesis, type VI secretion, and chromosome-associated functions. Concomitant with these differences, the nonmucoid variant displays reduced adherence to a CF lung bronchial cell line and reduced surface hydrophobicity and forms smaller cellular aggregates but has an increase in swimming and swarming motilities. Finally, analysis of the GC content of the upstream region of differentially expressed genes led to the identification of various genomic regions, possibly acquired by horizontal gene transfer, which were transcriptionally repressed by the increased expression of the Bmul_0158 gene in the 17616nmv strain. Taken together, the results revealed a significant role for this H-NS protein in the regulation of B. multivorans persistence- and virulence-associated genes. IMPORTANCE Members of the histone-like nucleoid structuring (H-NS) family of proteins, present in many bacteria, are important global regulators of gene expression. Many of the regulated genes were acquired horizontally and include pathogenicity islands and prophages, among others. Additionally, H-NS can play a structural role by bridging and compacting DNA, fulfilling a crucial role in cell physiology. Several virulence phenotypes have been frequently identified in several bacteria as dependent on H-NS activity. Here, we describe an H-NS-like protein of the opportunistic pathogen Burkholderia multivorans, a species commonly infecting the respiratory tract of cystic fibrosis patients. Our results indicate that this protein is involved in regulating virulence traits such as exopolysaccharide biosynthesis, adhesion to biotic surfaces, cellular aggregation, and motility. Furthermore, this H-NS-like protein is one out of eight orthologs present in the B. multivorans ATCC 17616 genome, posing relevant questions to be investigated on how these proteins coordinate the expression of virulence traits.

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Dataset Information

Molecular Basis for Environment Sensing by a Nucleoid-Structuring Bacterial Protein Filament.

Publications

Molecular Basis for Environment Sensing by a Nucleoid-Structuring Bacterial Protein Filament.

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