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Title: A glyoxal-specific aldehyde signaling axis in Pseudomonas aeruginosa that influences quorum sensing and infection
Abstract The universally conserved α-oxoaldehydes glyoxal (GO) and methylglyoxal (MGO) are toxic metabolic byproducts whose accumulation can lead to cell death. In the absence of a known, natural inducer of the GO-specific response in prokaryotes, we exploited RNA-seq to define a GO response in the bacterial pathogenPseudomonas aeruginosa. The highest upregulated operon consisted of the known glyoxalase (gloA2) and an antibiotic monooxygenase (ABM) domain of unknown function - renamed hereAldehyderesponsivequorum-sensingInhibitor (ArqI). ThearqI-gloA2operon is highly specific to GO induction and ArqI protein responds by migrating to the flagellar pole. An ArqI atomic structure revealed several unique features to the ABM family, including a ‘pinwheel’ hexamer harboring a GO-derived post-translational modification on a conserved arginine residue (Arg49). Induction of ArqI abrogates production of the Pseudomonas Quinolone Signal (PQS) quorum sensing molecule and was found to directly interact with PqsA; the first enzyme in the PQS biosynthesis pathway. Finally, we use a sepsis model of infection to reveal a survival requirement forarqI-gloA2in blood-rich organs (heart, spleen, liver and lung). Here we define a global GO response in a pathogen, identify and characterize the first GO-specific operon and implicate its role in PQS production and host survival.  more » « less
Award ID(s):
1734030
PAR ID:
10672160
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; more » ; ; ; ; « less
Publisher / Repository:
nature.com
Date Published:
Journal Name:
Nature Communications
Volume:
16
Issue:
1
ISSN:
2041-1723
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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