The rhl quorum-sensing (QS) system plays critical roles in the pathogenesis of P. aeruginosa. However, the regulatory effects that occur directly upstream of the rhl QS system are poorly understood. Here, we show that deletion of gene encoding for the two-component sensor BfmS leads to the activation of its cognate response regulator BfmR, which in turn directly binds to the promoter and decreases the expression of the rhlR gene that encodes the QS regulator RhlR, causing the inhibition of the rhl QS system. In the absence of bfmS, the Acka-Pta pathway can modulate the regulatory activity of BfmR. In addition, BfmS tunes the expression of 202 genes that comprise 3.6% of the P. aeruginosa genome. We further demonstrate that deletion of bfmS causes substantially reduced virulence in lettuce leaf, reduced cytotoxicity, enhanced invasion, and reduced bacterial survival during acute mouse lung infection. Intriguingly, specific missense mutations, which occur naturally in the bfmS gene in P. aeruginosa cystic fibrosis (CF) isolates such as DK2 strains and RP73 strain, can produce BfmS variants (BfmSL181P, BfmSL181P/E376Q, and BfmSR393H) that no longer repress, but instead activate BfmR. As a result, BfmS variants, but not the wild-type BfmS, inhibit the rhl QS system. This study thus uncovers a previously unexplored signal transduction pathway, BfmS/BfmR/RhlR, for the regulation of rhl QS in P. aeruginosa. We propose that BfmRS TCS may have an important role in the regulation and evolution of P. aeruginosa virulence during chronic infection in CF lungs.

Anion-scavenging materials tailored for 99 TcO 4 À trapping are urgently needed for both nuclear-related environmental remediation and management of spent nuclear fuel. For the first time, we report here an ultra-robust imidazolium-decorated covalent organic framework (COF) conjugate fabricated by an ionizing radiation strategy, for efficient capture of 99 TcO 4À . The charged imidazolium moieties are controllably anchored into the channel of the COF by simply adjusting the g-ray dose, thereby leading to tunable ReO 4 À uptake up to 952 mg g À1 with high selectivity and fast kinetics. More importantly, the high porosity and ultra-robust nanofiber structure of the COFs make them ideal packing materials for dynamic column experiments. >99.98% ReO 4 À /TcO 4 À can be efficiently separated and re-collected, even after four adsorptiondesorption cycles, ranking a new record of the elimination rate for ReO 4 À adsorption. The performance of these materials suggests attractive opportunities in practical applications for TcO 4 À removal from the environment and nuclear waste.