The DNA mimic protein BCAS0292 is involved in the regulation of virulence ofBurkholderia cenocepacia

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 that colonizes environmental niches, is exquisitely adaptable to the hypoxic environment of the cystic fibrosis lung and survives in macrophages. B. cenocepacia possesses a large genome encoding multiple virulence systems, stress response proteins and a large locus that responds to low oxygen. We previously identified BCAS0292, an acidic protein encoded on replicon 3. 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 ΔBCAS0292 mutant showed a range of pleiotropic effects: virulence, host-cell attachment and motility 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 electrostatic surface. Further, the ΔBCAS0292 mutant displayed altered DNA supercoiling, implicated in global regulation of gene expression. We propose that BCAS0292 acts as a DNA-mimic, altering DNA topology and regulating the expression of multiple genes, thereby enabling the adaptation of B. cenocepacia to highly diverse environments.

The Effects of Freeze-Thaw and UVC Radiation on Microbial Survivability in a Selected Mars-like Environment

“…This is due to the presence of the HU protein, which plays a crucial part in the organization and compaction of DNA in D. radiodurans . P. fungorum was also determined to be a highly UV resistant microbe, and while there is no published literature to support the existence of HU protein in P. fungorum , it has been shown that Paraburkholderia cenocepacia (a closely related strain) expresses HU protein [ 40 ]. Therefore, DNA compaction found within the nucleoid of both P. fungorum and D. radiodurans may facilitate a tolerance to DNA degradation caused by freeze-thaw conditions.…”