The OmpR regulator of Burkholderia multivorans controls mucoid-to-nonmucoid transition and other cell envelope properties associated with persistence in the cystic fibrosis lung

Abstract

Bacteria from the Burkholderia cepacia complex grow in different natural and man-made environments and are feared opportunistic pathogens that cause chronic respiratory infections in cystic fibrosis patients. Previous studies showed that Burkholderia mucoid clinical isolates grown under stress conditions give rise to nonmucoid variants devoid of the exopolysaccharide cepacian. Here, we determined that a major cause of the nonmucoid morphotype involves nonsynonymous mutations and small indels in the ompR gene encoding a response regulator of a twocomponent regulatory system. In trans complementation of nonmucoid variants (NMVs) with the native gene restored exopolysaccharide production. The loss of functional Burkholderia multivorans OmpR had positive effects on growth, adhesion to lung epithelial cells, and biofilm formation in high-osmolarity medium, as well as an increase in swimming and swarming motilities. In contrast, phenotypes such as antibiotic resistance, biofilm formation at low osmolarity, and virulence in Galleria mellonella were compromised by the absence of functional OmpR. Transcriptomic studies indicated that loss of the ompR gene affects the expression of 701 genes, many associated with outer membrane composition, motility, stress response, iron acquisition, and the uptake of nutrients, consistent with starvation tolerance. Since the stresses here imposed on B. multivorans may strongly resemble the ones found in the cystic fibrosis (CF) airways and mutations in the ompR gene from longitudinally collected CF isolates have been found, this regulator might be important for the production of NMVs in the CF environment.