Putting an end to the Pseudomonas aeruginosa IQS controversy

Abstract

Despite published evidence that IQS (2-(2-hydroxylphenyl)-thiazole-4-carbaldehyde) is in fact aeruginaldehyde, a by-product of the siderophore pyochelin biosynthesis or degradation and that the ambABCDE genes are not responsible for IQS synthesis, several authors, including in top review journals, perpetuate the wrong information. I hope that this short comment will clarify the situation once and for all. K E Y W O R D S aeruginaldehyde, IQS, Pseudomonas aeruginosa, pyochelin, quorum sensing 2 of 2 | CORNELIS al., 2014). In a very recent study, Trottmann et al. confirmed that aeruginaldehyde is derived from pyochelin since an incubation of the siderophore at 30°C resulted in the appearance of aeruginaldehyde (Trottmann et al., 2019). Ye et al. (2014) suggested that aeruginaldehyde could derive from dihydroaeruginoic acid (Dha) released from PchE during the assembly of the NRPS enzymes and the biosynthetic process (Ye et al., 2014). Interestingly, Maspoli, Wenner, Mislin, and Reimmann (2014) found in P. aeruginosa PA14 a genomic island containing genes for the biosynthesis of (enantio)pyochelin. Complementation of a pyochelin negative mutant with one NRPS gene led to the production of Dha (Maspoli et al., 2014). In a recent study, Sun et al. found that only the Rhl and PQS QS systems are involved in the regulation of phenazine production in a P. aeruginosa strain while mutants with deletions in amb or pch genes clusters were not affected in their production of phenazine compounds, excluding their possible participation in the QS circuitry (Sun, Zhou, Jin, Jiang, & He, 2016). | CON CLUS IONDespite the evidence presented here in this short commentary, still scientists publish articles, including reviews, mentioning IQS as the fourth quorum sensing molecule of P. aeruginosa being the product of AmbABCDE. The aim of this short comment is to clarify this point.

Surfactant phospholipids act as molecular switches for premature induction of quorum sensing-dependent virulence in Pseudomonas aeruginosa

“…Under in vitro experimental conditions, QS allows P. aeruginosa to communicate intercellularly via small, diffusible signaling molecules C12-HSL and C4-HSL, PQS, and IQS [ 32 – 35 ]. Local concentrations of signaling molecules increase at high cell densities, usually at the transition from late exponential to stationary growth phase, enter bacteria, and bind their corresponding transcriptional activators to activate the expression of virulence genes.…”

“…Local concentrations of signaling molecules increase at high cell densities, usually at the transition from late exponential to stationary growth phase, enter bacteria, and bind their corresponding transcriptional activators to activate the expression of virulence genes. The precise interplays among these QS systems remain to be defined, but they clearly regulate production of numerous virulence factors, including exoproteases, rhamnolipids, phenazines, exotoxin A, hydrogen cyanide, and biofilm formation [ 7 , 32 – 35 ]. In contrast, when small numbers of accidental microbes land within alveolar microcompartments, they need to multiply and promptly initiate counter strategies against host innate immune responses, among which include SP-A and SP-D-mediated opsonization and subsequent phagocytosis by residence alveolar macrophages; membrane permeabilization by SPA, SPD and other antimicrobial peptides; and cell wall degradation by lysozymes [ 20 , 21 , 44 – 48 ].…”

“…Although not fully delineated, it is generally accepted that the LasR-LasI sits on top of hierarchical order over RhlR-RhlI, PqsR-PQS, and PhoB-IQS QS circuits [ 7 , 31 – 35 , 61 , 62 ]. Because the expression of LasB and rhamnolipids is not induced by mouse BALF in the ∆ lasI ∆ rhII mutant, it is unlikely that PqsR and IQS signaling pathways, which act downstream of LasR, participate in the initial response to the induction by surfactant phospholipids.…”

“…Quorum sensing (QS) is a cell-to-cell communication system in Gram-negative bacteria that relies on population density, by producing and detecting the threshold levels of extracellular homoserine lactones, quinolones, and 2-(2-hydroxylphenyl)-thiazole-4-carbaldehyde (IQS) [ 32 – 35 ]. It is well known that the QS network of P. aeruginosa coordinates various activities, including virulence and biofilm formation.…”

“…Interestingly, a recent study indicates that under low phosphate conditions, the ambBCDE operon activated by an alternate effector PhoB, synthesizes IQS. In turn, IQS interacts with an unknown transcription factor to activate RhlR and PqsR signaling independent of LasR [ 34 , 35 ]. In this study, we examined the impact of alveolar surfactant on the modulation of QS-regulated virulence factors, including the production of exoproteases and rhamnolipids during acute pneumonia infection.…”