Transcriptional Regulators Controlling Virulence in Pseudomonas aeruginosa

Abstract

Pseudomonas aeruginosa is a pathogen capable of colonizing virtually every human tissue. The host colonization competence and versatility of this pathogen are powered by a wide array of virulence factors necessary in different steps of the infection process. This includes factors involved in bacterial motility and attachment, biofilm formation, the production and secretion of extracellular invasive enzymes and exotoxins, the production of toxic secondary metabolites, and the acquisition of iron. Expression of these virulence factors during infection is tightly regulated, which allows their production only when they are needed. This process optimizes host colonization and virulence. In this work, we review the intricate network of transcriptional regulators that control the expression of virulence factors in P. aeruginosa, including one- and two-component systems and σ factors. Because inhibition of virulence holds promise as a target for new antimicrobials, blocking the regulators that trigger the production of virulence determinants in P. aeruginosa is a promising strategy to fight this clinically relevant pathogen.

Keywords: Pseudomonas aeruginosa; one-component system; pathogenesis; quorum sensing; sigma factor; transcription regulators; two-component system; virulence.

Figure 1

Schematic representation showing the three main classes of transcriptional regulators in P. aeruginosa. Mechanisms underlying gene expression regulation by (a) one-component systems, (b) two-component systems, and (c) alternative σ factors. Positive and negative controls are represented with arrows and T-shaped lines, respectively. OM, outer membrane; CM, cytoplasmic membrane; RIP, regulated intramembrane proteolysis.

Figure 2

Regulation of virulence by quorum sensing in P. aeruginosa. The Las (depicted in pink), Rhl (depicted in purple), and PQS (depicted in blue) QS systems are governed by the OCS LasR, RhlR, and PqsR, respectively. Upon detection of their signal molecules, each OCS activates the expression of virulence factors and enzymes producing their respective inducing signals. Positive and negative regulations are represented with arrows and T-shaped lines, respectively.

Figure 3

Regulation of alginate production and virulence in P. aeruginosa. Alginate production in P. aeruginosa is controlled by the OCS AmrZ (depicted in yellow), the TCSs FimS-AlgR and KinB-AlgB (depicted in purple and green, respectively), and the σ^AlgT factor (depicted in blue). Positive and negative controls are represented with arrows and T-shaped lines, respectively. OM, outer membrane; CM, cytoplasmic membrane; RIP, regulated intramembrane proteolysis.

Figure 4

TCSs governing the switch between a planktonic lifestyle and biofilm formation via RsmA. The global regulator RsmA promotes a planktonic lifestyle by inducing motility and the production of T3SS in P. aeruginosa while blocking EPS production and biofilm formation. RsmA is antagonized by the two sRNAs RsmY and RsmZ. The TCSs GacS-GacR and BfiS-BfiR control RsmA activity by modulating RsmY and RsmZ levels. Positive and negative controls are represented with arrows and T-shaped lines, respectively. OM, outer membrane; CM, cytoplasmic membrane.