Title

Analysis of the Pseudomonas aeruginosa regulon controlled by the sensor kinase KinB and sigma factor RpoN

Document Type

Article

Publication Date

12-2011

Abstract

Alginate overproduction by P. aeruginosa, also known as mucoidy, is associated with chronic endobronchial infections in cystic fibrosis (CF). Alginate biosynthesis is initiated by the extracytoplasmic function sigma factor (σ(22), AlgU/T). In the wild type (wt) nonmucoid strains, such as PAO1, AlgU is sequestered to the cytoplasmic membrane by the anti-sigma factor MucA that inhibits alginate production. The mucA mutation that relieves AlgU from this sequestration is one mechanism underlying the conversion to mucoidy. However, the mucoid conversion can occur in wt mucA strains via the degradation of MucA by activated intramembrane proteases AlgW and/or MucP. Previously we reported that the deletion of the sensor kinase KinB in PAO1 induces an AlgW-dependent proteolysis of MucA resulting in alginate overproduction. This type of mucoid induction requires the alternate sigma factor RpoN (σ(54)). To determine the RpoN-dependent KinB regulon, microarray and proteomic analyses were performed on a mucoid kinB mutant and an isogenic nonmucoid kinB rpoN double mutant. In the kinB mutant of PAO1, RpoN controlled the expression of approximately 20% of the genome. Besides alginate biosynthetic and regulatory genes, KinB and RpoN also control a large number of genes including those involved in carbohydrate metabolism, quorum sensing, iron regulation, rhamnolipid production, and motility. In an acute pneumonia murine infection model, BALB/c mice exhibited increased survival when challenged with the kinB mutant than PAO1. Together, these data strongly suggest that KinB controls virulence factors important for the development of acute pneumonia and conversion to mucoidy.

Comments

This article first appeared in the winter 2011 issue of Journal of Bacteriology and is reprinted with permission.

Copyright © 2011, American Society for Microbiology

Publisher: author can archive post-print.

Access: Marshall University campus only.