BCAS0292 is involved in the adaptation of Burkholderia cenocepacia and shows characteristics of a DNA mimic protein AFFINITY PURIFICATION

ABSTRACT: Adaptation of opportunistic pathogens to their host environment requires reprogramming of a vast array of genes to facilitate host survival in the host. Burkholderia cenocepacia, a Gram-negative bacterium with a large genome of ~ 8Mb in size 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 resulted in altered abundance of >1000 proteins; 46 proteins became undetectable while 556 proteins showed >1.5-fold reduced abundance, suggesting BCAS0292 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. Structural analysis 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. Five proteins were identified in pull-downs with FLAG-tagged BCAS0292, including the Histone H1-like protein, HctB, recognised as a global transcriptional regulator. Taken together, we propose that BCAS0292 which is increased in abundance in response to stress, 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Bacteria Burkholderia Cenocepacia

TISSUE(S): Cell Culture

DISEASE(S): Cystic Fibrosis

SUBMITTER: Eugene Dillon  

LAB HEAD: Siobhán McClean

PROVIDER: PXD030041 | Pride | 2022-01-11

REPOSITORIES: Pride