Modulation of Host Biology by Pseudomonas aeruginosa Quorum Sensing Signal Molecules: Messengers or Traitors

Abstract

Bacterial cells sense their population density and respond accordingly by producing various signal molecules to the surrounding environments thereby trigger a plethora of gene expression. This regulatory pathway is termed quorum sensing (QS). Plenty of bacterial virulence factors are controlled by QS or QS-mediated regulatory systems and QS signal molecules (QSSMs) play crucial roles in bacterial signaling transduction. Moreover, bacterial QSSMs were shown to interfere with host cell signaling and modulate host immune responses. QSSMs not only regulate the expression of bacterial virulence factors but themselves act in the modulation of host biology that can be potential therapeutic targets.

Keywords: N-acyl homoserine lactones; Pseudomonas aeruginosa; Pseudomonas quinolone signal; Quorum sensing; immunomodulation.

FIGURE 1

Schematic illustration of the best characterized Pseudomonas aeruginosa quorum sensing signal molecules (QSSMs) that interfere with mammalian host biological functions. P. aeruginosa 3-oxo-C12-HSL targets XBP1 and paraoxonase 2 leading to host cell apoptosis, and the binding of 3-oxo-C12-HSL with IQGAP1 impairs the host cell integrity. 3-oxo-C12-HSL modulates innate immune responses via the activation of T2R38 receptor and inhibition of NF-κB pathways. P. aeruginosa Pseudomonas quinolone signal (PQS) molecule induces MSCs apoptosis, induces the secretion of inflammatory cytokines via the inhibition NF-κB and HIP-1α pathways. PQS molecule interferes with neutrophils chemotaxis potentially through the activation of p38 MAPK pathways. See text for details. PLCβ2, phospholipase C β2; TRPM5, transient receptor potential cation channel subfamily M member 5; PPARs, peroxisome proliferator-activated receptors; TJ, tight junction; AJ, adhesional junction; MAPK, mitogen-activated protein kinase; MSCs, mesenchymal stem cells.