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...
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2025-07-01
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| Online Access: | https://doi.org/10.1038/s41467-025-61469-8 |
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| author | Christopher J. Corcoran Bonnie J. Cuthbert David G. Glanville Mailyn Terrado Diana Valverde Mendez Benjamin P. Bratton Daniel E. Schemenauer Valerie L. Tokars Thomas G. Martin Lawrence W. Rasmussen Matthew C. Madison Andrew F. Maule Joshua W. Shaevitz Boo Shan Tseng Julian P. Whitelegge Catherine Putonti Amit Gaggar Jordan R. Beach Jonathan A. Kirk Alfonso Mondragón Abby R. Kroken Jonathan P. Allen Celia W. Goulding Andrew T. Ulijasz |
| author_facet | Christopher J. Corcoran Bonnie J. Cuthbert David G. Glanville Mailyn Terrado Diana Valverde Mendez Benjamin P. Bratton Daniel E. Schemenauer Valerie L. Tokars Thomas G. Martin Lawrence W. Rasmussen Matthew C. Madison Andrew F. Maule Joshua W. Shaevitz Boo Shan Tseng Julian P. Whitelegge Catherine Putonti Amit Gaggar Jordan R. Beach Jonathan A. Kirk Alfonso Mondragón Abby R. Kroken Jonathan P. Allen Celia W. Goulding Andrew T. Ulijasz |
| author_sort | Christopher J. Corcoran |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-51e3ce5f23ff4da2abb45d98385979e1 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-51e3ce5f23ff4da2abb45d98385979e12025-08-20T03:43:00ZengNature PortfolioNature Communications2041-17232025-07-0116112410.1038/s41467-025-61469-8A glyoxal-specific aldehyde signaling axis in Pseudomonas aeruginosa that influences quorum sensing and infectionChristopher J. Corcoran0Bonnie J. Cuthbert1David G. Glanville2Mailyn Terrado3Diana Valverde Mendez4Benjamin P. Bratton5Daniel E. Schemenauer6Valerie L. Tokars7Thomas G. Martin8Lawrence W. Rasmussen9Matthew C. Madison10Andrew F. Maule11Joshua W. Shaevitz12Boo Shan Tseng13Julian P. Whitelegge14Catherine Putonti15Amit Gaggar16Jordan R. Beach17Jonathan A. Kirk18Alfonso Mondragón19Abby R. Kroken20Jonathan P. Allen21Celia W. Goulding22Andrew T. Ulijasz23Department of Microbiology and Immunology, Loyola University ChicagoDepartment of Molecular Biology and Biochemistry, University of California, IrvineDepartment of Medicine, Division of Pulmonary, Allergy and Critical Care, Department of Medicine, University of Alabama at BirminghamDepartment of Microbiology and Immunology, Loyola University ChicagoLewis-Sigler Institute of Integrative Genomics, Princeton UniversityDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical CenterDepartment of Microbiology and Immunology, Loyola University ChicagoDepartment of Molecular Pharmacology and Biological Chemistry, Northwestern UniversityDepartment of Cell and Molecular Physiology, Loyola University Chicago Stritch School of MedicineDepartment of Medicine, Division of Pulmonary, Allergy and Critical Care, Department of Medicine, University of Alabama at BirminghamDepartment of Medicine, Division of Pulmonary, Allergy and Critical Care, Department of Medicine, University of Alabama at BirminghamDepartment of Plant and Agroecosystem Sciences, University of Wisconsin-MadisonLewis-Sigler Institute of Integrative Genomics, Princeton UniversitySchool of Life Sciences, University of Nevada Las VegasDepartment of Chemistry and Biochemistry, University of California, Los AngelesDepartment of Biology, Loyola University ChicagoDepartment of Medicine, Division of Pulmonary, Allergy and Critical Care, Department of Medicine, University of Alabama at BirminghamDepartment of Cell and Molecular Physiology, Loyola University Chicago Stritch School of MedicineDepartment of Cell and Molecular Physiology, Loyola University Chicago Stritch School of MedicineDepartment of Molecular Biosciences, Northwestern UniversityDepartment of Microbiology and Immunology, Loyola University ChicagoDepartment of Microbiology and Immunology, Loyola University ChicagoDepartment of Pharmaceutical Sciences & Molecular Biology & Biochemistry, University of California IrvineDepartment of Medicine, Division of Pulmonary, Allergy and Critical Care, Department of Medicine, University of Alabama at BirminghamAbstract 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.https://doi.org/10.1038/s41467-025-61469-8 |
| spellingShingle | Christopher J. Corcoran Bonnie J. Cuthbert David G. Glanville Mailyn Terrado Diana Valverde Mendez Benjamin P. Bratton Daniel E. Schemenauer Valerie L. Tokars Thomas G. Martin Lawrence W. Rasmussen Matthew C. Madison Andrew F. Maule Joshua W. Shaevitz Boo Shan Tseng Julian P. Whitelegge Catherine Putonti Amit Gaggar Jordan R. Beach Jonathan A. Kirk Alfonso Mondragón Abby R. Kroken Jonathan P. Allen Celia W. Goulding Andrew T. Ulijasz A glyoxal-specific aldehyde signaling axis in Pseudomonas aeruginosa that influences quorum sensing and infection Nature Communications |
| title | A glyoxal-specific aldehyde signaling axis in Pseudomonas aeruginosa that influences quorum sensing and infection |
| title_full | A glyoxal-specific aldehyde signaling axis in Pseudomonas aeruginosa that influences quorum sensing and infection |
| title_fullStr | A glyoxal-specific aldehyde signaling axis in Pseudomonas aeruginosa that influences quorum sensing and infection |
| title_full_unstemmed | A glyoxal-specific aldehyde signaling axis in Pseudomonas aeruginosa that influences quorum sensing and infection |
| title_short | A glyoxal-specific aldehyde signaling axis in Pseudomonas aeruginosa that influences quorum sensing and infection |
| title_sort | glyoxal specific aldehyde signaling axis in pseudomonas aeruginosa that influences quorum sensing and infection |
| url | https://doi.org/10.1038/s41467-025-61469-8 |
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