Protein with negative surface charge distribution, Bnr1, shows characteristics of a DNA‐mimic protein and may be involved in the adaptation of Burkholderia cenocepacia

MicrobiologyOpen

Simon Dignam¹  Ruth Dennehy¹  Siobhán McClean¹  Zuzanna Drulis‐Kawa²  Maria Romano³  Rita Berisio³  Sarah McCormack⁴  Yueran Hou⁴  Niamh Duggan⁴  Laura Ardill⁴  Tadhg Ó'Cróinín⁴  Matthew V. X. Whelan⁴  Jessica Molony⁴  Miguel A. Valvano⁵  Eugene Dillon⁶ 

[1] Centre of Microbial Host Interactions Institute of Technology Tallaght Dublin Ireland;Department of Pathogen Biology and Immunology, Institute of Genetics and Microbiology University of Wroclaw Wroclaw Poland;Institute of Biostructures and Bioimaging National Research Council Naples Italy;School of Biomolecular and Biomedical Science University College Dublin Dublin Ireland;School of Medicine, Dentistry and Biomedical Sciences, Wellcome‐Wolfson Institute for Experimental Medicine Queen's University Belfast Belfast UK;UCD Conway Institute of Biomolecular and Biomedical Research University College Dublin Belfield, Dublin Ireland;

关键词: bacterial adaptation;    Burkholderia cenocepacia;    chronic infection;    cystic fibrosis;    DNA‐mimic protein;    protein–protein interaction;   

DOI  :  10.1002/mbo3.1264

来源: DOAJ

【 摘 要 】

Abstract Adaptation of opportunistic pathogens to their host environment requires reprogramming of a vast array of genes to facilitate survival in the host. Burkholderia cenocepacia, a Gram‐negative bacterium with a large genome of ∼8 Mb that colonizes environmental niches, is exquisitely adaptable to the hypoxic environment of the cystic fibrosis lung and survives in macrophages. We previously identified an immunoreactive acidic protein encoded on replicon 3, BCAS0292. Deletion of the BCAS0292 gene significantly altered the abundance of 979 proteins by 1.5‐fold or more; 19 proteins became undetectable while 545 proteins showed ≥1.5‐fold reduced abundance, suggesting the BCAS0292 protein is a global regulator. Moreover, the ∆BCAS0292 mutant showed a range of pleiotropic effects: virulence and host‐cell attachment were reduced, antibiotic susceptibility was altered, and biofilm formation enhanced. Its growth and survival were impaired in 6% oxygen. In silico prediction of its three‐dimensional structure revealed BCAS0292 presents a dimeric β‐structure with a negative surface charge. The ΔBCAS0292 mutant displayed altered DNA supercoiling, implicated in global regulation of gene expression. Three proteins were identified in pull‐downs with FLAG‐tagged BCAS0292, including the Histone H1‐like protein, HctB, which is recognized as a global transcriptional regulator. We propose that BCAS0292 protein, which we have named Burkholderia negatively surface‐charged regulatory protein 1 (Bnr1), acts as a DNA‐mimic and binds to DNA‐binding proteins, altering DNA topology and regulating the expression of multiple genes, thereby enabling the adaptation of B. cenocepacia to highly diverse environments.

【 授权许可】

Unknown