Snapshots of Pseudomonas aeruginosa SOS response reveal structural requisites for LexA autoproteolysis
Summary: Antimicrobial resistance poses a severe threat to human health and Pseudomonas aeruginosa stands out among the pathogens responsible for this emergency. The SOS response to DNA damage is crucial in bacterial evolution, influencing resistance development and adaptability in challenging envir...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224029535 |
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| author | Filippo Vascon Sofia De Felice Matteo Gasparotto Stefan T. Huber Claudio Catalano Monica Chinellato Riccardo Mezzetti Alessandro Grinzato Francesco Filippini Lorenzo Maso Arjen J. Jakobi Laura Cendron |
| author_facet | Filippo Vascon Sofia De Felice Matteo Gasparotto Stefan T. Huber Claudio Catalano Monica Chinellato Riccardo Mezzetti Alessandro Grinzato Francesco Filippini Lorenzo Maso Arjen J. Jakobi Laura Cendron |
| author_sort | Filippo Vascon |
| collection | DOAJ |
| description | Summary: Antimicrobial resistance poses a severe threat to human health and Pseudomonas aeruginosa stands out among the pathogens responsible for this emergency. The SOS response to DNA damage is crucial in bacterial evolution, influencing resistance development and adaptability in challenging environments, especially under antibiotic exposure. Recombinase A (RecA) and the transcriptional repressor LexA are the key players that orchestrate this process, determining either the silencing or the active transcription of the genes under their control. By integrating state-of-the-art structural approaches with in vitro binding and functional assays, we elucidated the molecular events activating the SOS response in P. aeruginosa, focusing on the RecA-LexA interaction. Our findings identify the conserved determinants and strength of the interactions that allow RecA to trigger LexA autocleavage and inactivation. These results provide the groundwork for designing novel antimicrobial strategies and exploring the potential translation of Escherichia coli-derived approaches, to address the implications of P. aeruginosa infections. |
| format | Article |
| id | doaj-art-81818c3474c3453ca00495c25fece21b |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-81818c3474c3453ca00495c25fece21b2025-01-19T06:26:30ZengElsevieriScience2589-00422025-02-01282111726Snapshots of Pseudomonas aeruginosa SOS response reveal structural requisites for LexA autoproteolysisFilippo Vascon0Sofia De Felice1Matteo Gasparotto2Stefan T. Huber3Claudio Catalano4Monica Chinellato5Riccardo Mezzetti6Alessandro Grinzato7Francesco Filippini8Lorenzo Maso9Arjen J. Jakobi10Laura Cendron11Department of Biology, University of Padua, Via Ugo Bassi 58/b, 35131 Padova, ItalyDepartment of Biology, University of Padua, Via Ugo Bassi 58/b, 35131 Padova, ItalyDepartment of Biology, University of Padua, Via Ugo Bassi 58/b, 35131 Padova, Italy; Department of Translational Brain Research, Central Institute of Mental Health (ZI), University of Heidelberg/Medical Faculty Mannheim, 68159 Mannheim, GermanyDepartment of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, 2628CD Delft, the NetherlandsNanoImaging Services, 4940 Carroll Canyon Road, Suite 115, San Diego, CA 92121, USADepartment of Biology, University of Padua, Via Ugo Bassi 58/b, 35131 Padova, Italy; Department of Medicine, University of Padua, Via Giustiniani 2, 35121 Padova, ItalyDepartment of Biology, University of Padua, Via Ugo Bassi 58/b, 35131 Padova, ItalyDepartment of Biology, University of Padua, Via Ugo Bassi 58/b, 35131 Padova, Italy; CM01 Beamline, European Synchrotron Radiation Facility (ESRF), Grenoble, FranceDepartment of Biology, University of Padua, Via Ugo Bassi 58/b, 35131 Padova, ItalyDepartment of Biology, University of Padua, Via Ugo Bassi 58/b, 35131 Padova, Italy; Aethon Therapeutics, Long Island City, NY 11101, USADepartment of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, 2628CD Delft, the NetherlandsDepartment of Biology, University of Padua, Via Ugo Bassi 58/b, 35131 Padova, Italy; Corresponding authorSummary: Antimicrobial resistance poses a severe threat to human health and Pseudomonas aeruginosa stands out among the pathogens responsible for this emergency. The SOS response to DNA damage is crucial in bacterial evolution, influencing resistance development and adaptability in challenging environments, especially under antibiotic exposure. Recombinase A (RecA) and the transcriptional repressor LexA are the key players that orchestrate this process, determining either the silencing or the active transcription of the genes under their control. By integrating state-of-the-art structural approaches with in vitro binding and functional assays, we elucidated the molecular events activating the SOS response in P. aeruginosa, focusing on the RecA-LexA interaction. Our findings identify the conserved determinants and strength of the interactions that allow RecA to trigger LexA autocleavage and inactivation. These results provide the groundwork for designing novel antimicrobial strategies and exploring the potential translation of Escherichia coli-derived approaches, to address the implications of P. aeruginosa infections.http://www.sciencedirect.com/science/article/pii/S2589004224029535Natural sciencesBiological sciencesMicrobiologyBiophysics |
| spellingShingle | Filippo Vascon Sofia De Felice Matteo Gasparotto Stefan T. Huber Claudio Catalano Monica Chinellato Riccardo Mezzetti Alessandro Grinzato Francesco Filippini Lorenzo Maso Arjen J. Jakobi Laura Cendron Snapshots of Pseudomonas aeruginosa SOS response reveal structural requisites for LexA autoproteolysis iScience Natural sciences Biological sciences Microbiology Biophysics |
| title | Snapshots of Pseudomonas aeruginosa SOS response reveal structural requisites for LexA autoproteolysis |
| title_full | Snapshots of Pseudomonas aeruginosa SOS response reveal structural requisites for LexA autoproteolysis |
| title_fullStr | Snapshots of Pseudomonas aeruginosa SOS response reveal structural requisites for LexA autoproteolysis |
| title_full_unstemmed | Snapshots of Pseudomonas aeruginosa SOS response reveal structural requisites for LexA autoproteolysis |
| title_short | Snapshots of Pseudomonas aeruginosa SOS response reveal structural requisites for LexA autoproteolysis |
| title_sort | snapshots of pseudomonas aeruginosa sos response reveal structural requisites for lexa autoproteolysis |
| topic | Natural sciences Biological sciences Microbiology Biophysics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224029535 |
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