A glyoxal-specific aldehyde signaling axis in Pseudomonas aeruginosa that influences quorum sensing and infection

Authors

• Christopher J. Corcoran, Loyola University Chicago
• Bonnie J. Cuthbert, University of California, Irvine
• David G. Glanville, Division of Pulmonary, Allergy and Critical Care Medicine
• Mailyn Terrado, Loyola University Chicago
• Diana Valverde Mendez, Princeton University
• Benjamin P. Bratton, Vanderbilt University Medical Center
• Daniel E. Schemenauer, Loyola University Chicago
• Valerie L. Tokars, Northwestern University
• Thomas G. Martin, Stritch School of Medicine
• Lawrence W. Rasmussen, Division of Pulmonary, Allergy and Critical Care Medicine
• Matthew C. Madison, Division of Pulmonary, Allergy and Critical Care Medicine
• Andrew F. Maule, University of Wisconsin-Madison
• Joshua W. Shaevitz, Princeton University
• Boo Shan Tseng, University of Nevada, Las Vegas
• Julian P. Whitelegge, University of California, Los Angeles
• Catherine Putonti, Loyola University Chicago
• Amit Gaggar, Division of Pulmonary, Allergy and Critical Care Medicine
• Jordan R. Beach, Stritch School of Medicine
• Jonathan A. Kirk, Stritch School of Medicine
• Alfonso Mondragón, Northwestern University
• Abby R. Kroken, Loyola University Chicago
• Jonathan P. Allen, Loyola University Chicago
• Celia W. Goulding, University of California, Irvine
• Andrew T. Ulijasz, Division of Pulmonary, Allergy and Critical Care Medicine

Document Type

Article

Publication Date

7-18-2025

Publication Title

Nature Communications

Volume

16

Issue

1

Pages

1-24

Publisher Name

Nature Connections

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 pathogen Pseudomonas aeruginosa. The highest upregulated operon consisted of the known glyoxalase (gloA2) and an antibiotic monooxygenase (ABM) domain of unknown function - renamed here Aldehyde responsive quorum-sensing Inhibitor (ArqI). The arqI-gloA2 operon 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 for arqI-gloA2 in 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.

Identifier

105011055767

Comments

Author Posting © The Author(s), 2025. This article is posted here by permission of Nature Communicatins for personal use and non-commercial redistribution. This article was published open access in Nature Communications, Vol. 16, Iss. 1 (July 2025), https://doi.org/10.1038/s41467-025-61469-8.

Recommended Citation

Corcoran, Christopher J.; Cuthbert, Bonnie J.; Glanville, David G.; Terrado, Mailyn; Valverde Mendez, Diana; Bratton, Benjamin P.; Schemenauer, Daniel E.; Tokars, Valerie L.; Martin, Thomas G.; Rasmussen, Lawrence W.; Madison, Matthew C.; Maule, Andrew F.; Shaevitz, Joshua W.; Tseng, Boo Shan; Whitelegge, Julian P.; Putonti, Catherine; Gaggar, Amit; Beach, Jordan R.; Kirk, Jonathan A.; Mondragón, Alfonso; Kroken, Abby R.; Allen, Jonathan P.; Goulding, Celia W.; and Ulijasz, Andrew T.. A glyoxal-specific aldehyde signaling axis in Pseudomonas aeruginosa that influences quorum sensing and infection. Nature Communications, 16, 1: 1-24, 2025. Retrieved from Loyola eCommons, Biology: Faculty Publications and Other Works, http://dx.doi.org/10.1038/s41467-025-61469-8

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Copyright Statement

© Nature Communication, 2025.