6cb4f01606eb5b9ae4a2c00b8887c1dc pmc_10304680.pdf c45f9d5efac6b5c505304bb80c908a20cf901ae5 pmc_10304680.pdf ad01f490d33b886759d92dd1e12cf2610aaa67a47f4a105f6d1d00506256bac7 pmc_10304680.pdf Title: A Stenotrophomonas maltophilia TetR-Like Transcriptional Regulator Involved in Fatty Acid Metabolism Is Controlled by Quorum Sensing Signals Subject: Genetics and Molecular Biology Keywords: quorum sensing; N-acyl homoserine lactones; DSF; fatty acid metabolism; TetR-like regulator; Stenotrophomonas Author: Xavier Coves;Marc Bravo;Pol Huedo;Òscar Conchillo-Solé;Andromeda-Celeste Gómez;Anna Esteve-Codina;Marc Dabad;Marta Gut;Xavier Daura;Daniel Yero;Isidre Gibert Creator: PTC Arbortext Advanced Print Publisher 11.1.4012/W Producer: Adobe LiveCycle PDF Generator; modified using iText® 5.5.13.2 ©2000-2020 iText Group NV (AGPL-version) CreationDate: Fri Jun 16 05:25:43 2023 CEST ModDate: Mon Jun 19 15:58:14 2023 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 17 Encrypted: no Page size: 584.957 x 782.986 pts Page rot: 0 File size: 1626153 bytes Optimized: no PDF version: 1.4 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- PPLOGD+AdvOTce3d9a73 Type 1C WinAnsi yes yes no 111 0 PPLOGE+AdvOT56309c18.I Type 1C WinAnsi yes yes no 112 0 PPLOJE+AdvOT07517017 Type 1C WinAnsi yes yes no 597 0 PPLOJF+AdvOT3b30f6db.B Type 1C WinAnsi yes yes no 41 0 PPLOKG+AdvOT65f8a23b.I Type 1C WinAnsi yes yes no 42 0 PPLOKH+AdvOT46dcae81 Type 1C WinAnsi yes yes no 43 0 PPLOKI+AdvP7DA6 Type 1C WinAnsi yes yes no 65 0 PPLOKJ+AdvOT46dcae81+fb Type 1C Custom yes yes yes 44 0 PPLOKK+AdvOT07517017+fb Type 1C Custom yes yes yes 598 0 PPLOMK+AdvOT46dcae81+20 Type 1C WinAnsi yes yes no 45 0 PPLOOK+AdvOTd0125be5.BI Type 1C WinAnsi yes yes no 66 0 PPLOOL+AdvP80675 Type 1C WinAnsi yes yes no 67 0 PPMBNJ+AdvOT8817665d Type 1C WinAnsi yes yes no 90 0 PPMBOK+AdvPSUnvGMP Type 1C WinAnsi yes yes no 113 0 PPMCBJ+AdvOT3b30f6db.B+fb Type 1C Custom yes yes yes 139 0 PPMDAE+AdvOTb214af43 Type 1C WinAnsi yes yes no 153 0 PPMDEE+AdvPSMP13 Type 1C WinAnsi yes yes no 217 0 PPMDGE+AdvP4C4E74 Type 1C Custom yes yes no 246 0 PPMDIE+AdvOTce3d9a73+20 Type 1C WinAnsi yes yes no 255 0 PPMDME+AdvP4C4E59 Type 1C Custom yes yes no 338 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-10-26 02:25:15 CEST RepresentationInformation: pmc_10304680.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-10-18 02:19:10 CEST Size: 1626153 Format: PDF Version: 1.4 Status: Well-Formed, but not valid SignatureMatches: PDF-hul ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - 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Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612679d6 Item: Title: QS signal-induced genes are also deregulated in stationary-phase cells of S. maltophilia. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@11758f2a Item: Title: Smlt2053 is a transcriptional regulator that autoregulates its own operon. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@e720b71 Item: Title: Fatty acids, including DSF, affect the binding of Smlt2053 to its promoter. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1b26f7b2 Item: Title: Smlt2053 participates in biofilm formation in S. maltophilia. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@491cc5c9 Item: Title: DISCUSSION Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@74ad1f1f Item: Title: MATERIALS AND METHODS Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6a1aab78 Children: Item: Title: Bacterial strains and reagents. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@462d5aee Item: Title: Growth conditions and growth curves. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@69b0fd6f Item: Title: Culture conditions and RNA extractions for RNA-seq. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@757942a1 Item: Title: RNA library construction and sequencing. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4a87761d Item: Title: RNA-seq data and sequence analysis. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@66d1af89 Item: Title: Quantitative real-time PCR analysis. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@8646db9 Item: Title: Construction of unmarked deletion mutants. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@37374a5e Item: Title: Protein production and purification. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4671e53b Item: Title: EMSAs. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@2db7a79b Item: Title: DSF extraction, detection, and quantification. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6950e31 Item: Title: Biofilm formation. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@b7dd107 Item: Title: Analysis of cellular fatty acids. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@42eca56e Item: Title: Statistical analysis. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@52f759d7 Item: Title: Data availability. Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7cbd213e Item: Title: SUPPLEMENTAL MATERIAL Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@192d3247 Item: Title: ACKNOWLEDGMENTS Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3ecd23d9 Item: Title: REFERENCES Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@569cfc36 Info: Title: A Stenotrophomonas maltophilia TetR-Like Transcriptional Regulator Involved in Fatty Acid Metabolism Is Controlled by Quorum Sensing Signals Author: Xavier Coves;Marc Bravo;Pol Huedo;Òscar Conchillo-Solé;Andromeda-Celeste Gómez;Anna Esteve-Codina;Marc Dabad;Marta Gut;Xavier Daura;Daniel Yero;Isidre Gibert Subject: Genetics and Molecular Biology Keywords: quorum sensing; N-acyl homoserine lactones; DSF; fatty acid metabolism; TetR-like regulator; Stenotrophomonas Creator: PTC Arbortext Advanced Print Publisher 11.1.4012/W Producer: Adobe LiveCycle PDF Generator; modified using iText® 5.5.13.2 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Fatty Acid Metabolism Is Controlled by Quorum Sensing Signals 10.1128/aem.00635-23 Xavier Coves Marc Bravo Pol Huedo Òscar Conchillo-Solé Andromeda-Celeste Gómez Anna Esteve-Codina Marc Dabad Marta Gut Xavier Daura Daniel Yero Isidre Gibert Genetics and Molecular Biology Genetics and Molecular Biology quorum sensing N-acyl homoserine lactones DSF fatty acid metabolism TetR-like regulator Stenotrophomonas American Society for Microbiology Coves et al. Copyright © 2023 Coves et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. 20230605 2023 ABSTRACT Stenotrophomonas maltophilia is an environmental bacterium as well as an emerging opportunistic multidrug-resistant pathogen. They use the endogenous diffusible signal factor (DSF) quorum sensing (QS) system to coordinate population behavior and regulate virulence processes but can also respond to exogenous N-acyl-homoserine lactone (AHL) signals produced by neighboring bacteria. The effect of these QS signals on the global gene expression of this species remains, however, unknown. Whole-transcriptome sequencing analyses were performed for exponential cultures of S. maltophilia K279a treated with exogenous DSF or AHLs. Addition of DSF and AHLs signals resulted in changes in expression of at least 2-fold for 28 and 82 genes, respectively. Interestingly, 22 of these genes were found upregulated by both QS signals, 14 of which were shown to also be induced during the stationary phase. Gene functions regulated by all conditions included lipid and amino acid metabolism, stress response and signal transduction, nitrogen and iron metabolism, and adaptation to microoxic conditions. Among the common top upregulated QS core genes, a putative TetR-like regulator (locus tag SMLT2053) was selected for functional characterization. This regulator controls its own β-oxidation operon (Smlt2053-Smlt2051), and it is found to sense long-chain fatty acids (FAs), including the QS signal DSF. Gene knockout experiments reveal that operon Smlt2053-Smlt2051 is involved in biofilm formation. Overall, our findings provide clues on the effect that QS signals have in S. maltophilia QS-related phenotypes and the transition from the exponential to the stationary phase and bacterial fitness under high-density growth. IMPORTANCE The quorum sensing system in Stenotrophomonas maltophilia, in addition to coordinating the bacterial population, controls virulence-associated phenotypes, such as biofilm formation, motility, protease production, and antibiotic resistance mechanisms. Biofilm formation is frequently associated with the persistence and chronic nature of nosocomial infections. In addition, biofilms exhibit high resistance to antibiotics, making treatment of these infections extremely difficult. The importance of studying the metabolic and regulatory systems controlled by quorum sensing autoinducers will make it possible to discover new targets to control pathogenicity mechanisms in S. maltophilia. 20230418 20230515 1098-5336 Pages: Page: Label: 1 Annotations: Annotation: Subtype: Link Rect: 215, 554, 260, 563 Annotation: Subtype: Link Rect: 281, 554, 329, 563 Annotation: Subtype: Link Rect: 410, 133, 506, 140 Annotation: Subtype: Link Rect: 400, 124, 456, 131 Annotation: Subtype: Link Rect: 459, 24, 526, 31 Annotation: Subtype: Link Rect: 508, 683, 544, 719 Page: Label: 2 Annotations: Annotation: Subtype: Link Rect: 201, 653, 206, 662 Destination: 258 Annotation: Subtype: Link Rect: 231, 616, 235, 625 Destination: 258 Annotation: Subtype: Link Rect: 235, 616, 239, 625 Destination: null Annotation: Subtype: Link Rect: 239, 616, 244, 625 Destination: 258 Annotation: Subtype: Link Rect: 44, 543, 48, 552 Destination: 258 Annotation: Subtype: Link Rect: 52, 543, 57, 552 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