Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.06.226779v1?rss=1 Authors: Dennehy, R., Dignam, S., McCormack, S., Romano, M., Hou, Y., Ardill, L., Whelan, M. V., Drulis-Kawa, Z., O Croinin, T., Valvano, M. A., Berisio, R., McClean, S. 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 {triangleup}BCAS0292 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 {beta}-structure with a negative electrostatic surface. Further, the {Delta}BCAS0292 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. Copy rights belong to original authors. Visit the link for more info