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The multi-output incoherent feedforward loop constituted by the transcriptional regulators LasR and RsaL confers robustness to a subset of quorum sensing genes in Pseudomonas aeruginosa
Abstract
Quorum sensing (QS) is an intercellular communication system which controls virulence-related phenotypes in the human pathogen Pseudomonas aeruginosa. LasR is the QS receptor protein which responds to the signal molecule N-(3-oxododecanoyl)homoserine lactone (3OC12-HSL) and promotes signal production by increasing the transcription of the 3OC12-HSL synthase gene, lasI. LasR also activates the expression of other genes, including rsaL, coding for the RsaL protein which acts as a transcriptional repressor of lasI. Direct gene activation and RsaL-mediated gene repression, both exerted by LasR on the expression of the output gene lasI, generate a regulatory network motif known as the type 1 incoherent feedforward loop (IFFL-1) that governs 3OC12-HSL production. In addition to lasI, RsaL directly represses a set of LasR-activated genes; hence, the IFFL-1 generated by LasR and RsaL is a multi-output IFFL-1. Here we demonstrate that the multi-output IFFL-1 constituted by LasR and RsaL confers robustness with respect to fluctuations in the levels of LasR to the phenotypes controlled by both these transcriptional regulators (e.g. 3OC12-HSL synthesis and pyocyanin production). In contrast, other virulence-related phenotypes controlled by LasR but not by RsaL (e.g. elastase and protease production) are sensitive to changes in LasR levels. Overall, the multi-output IFFL-1 generated by LasR and RsaL splits the QS regulon into two distinct sub-regulons with different robustness with respect to LasR fluctuations. This emerging regulatory property enhances the phenotypic plasticity of P. aeruginosa, thus contributing to its adaptation to changing environments.
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“RsaL is a transcriptional regulator that represses both the lasI gene and its own expression, establishing a negative feedback loop that limits the accumulation of 3OC12-HSL beyond physiologically beneficial levels71.”
From Pseudomonas aeruginosa: ecology, evolution, pathogenesis and antimicrobial susceptibility (2025) · cites this paper as [71]
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Chevrier, N., Mertins, P., Artyomov, M. N., Shalek, A. K., Iannacone, M., Ciaccio, M. F., Gat-Viks, I., Tonti, E., DeGrace, M. M., Clauser, K. R., et al. (2011) · Cell · doi:10.1016/j.cell.2011.10.022 · Cited by 179
Genetic regulatory networks programming hematopoietic stem cells and erythroid lineage specification
Swiers, G., Patient, R., & Loose, M. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.02.051 · Cited by 168
The Utility of Paradoxical Components in Biological Circuits
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Research works printed but not linked: 66
- Milo, 2002, Network motifs: simple building blocks of complex networks, Science, 298, 824, 10.1126/science.298.5594.824 · DOI · Paper page
- Alon, 2007, Network motifs: theory and experimental approaches, Nat. Rev. Genet., 8, 450, 10.1038/nrg2102 · DOI · Paper page
- Mangan, 2003, Structure and function of the feed-forward loop network motif, Proc. Natl. Acad. Sci. U. S. A., 100, 11980, 10.1073/pnas.2133841100 · DOI · Paper page
- Lee, 2002, Transcriptional regulatory networks in Saccharomyces cerevisiae, Science, 298, 799, 10.1126/science.1075090 · DOI · Paper page
- Boyer, 2005, Core transcriptional regulatory circuitry in human embryonic stem cells, Cell, 122, 947, 10.1016/j.cell.2005.08.020 · DOI · Paper page
- MacGillavry, 2009, NFIL3 and cAMP response element-binding protein form a transcriptional feedforward loop that controls neuronal regeneration-associated gene expression, J. Neurosci., 29, 15542, 10.1523/JNEUROSCI.3938-09.2009 · DOI
- Johnston Jr, 2011, Interlocked feedforward loops control cell-type-specific Rhodopsin expression in the Drosophila eye, Cell, 145, 956, 10.1016/j.cell.2011.05.003 · DOI
- Takeda, 2012, Incoherent feedforward control governs adaptation of activated Ras in a eukaryotic chemotaxis pathway, Sci. Signaling, 5, ra2, 10.1126/scisignal.2002413 · DOI · Paper page
- Nakajima, 2014, Rectified directional sensing in long-range cell migration, Nat. Commun., 5, 5367, 10.1038/ncomms6367 · DOI
- Bu, 2016, A miR-34a-Numb feedforward loop triggered by inflammation regulates asymmetric stem cell division in intestine and colon cancer, Cell Stem Cell, 18, 189, 10.1016/j.stem.2016.01.006 · DOI · Paper page
- Eichenberger, 2004, The program of gene transcription for a single differentiating cell type during sporulation in Bacillus subtilis, PLoS Biol., 2, e328, 10.1371/journal.pbio.0020328 · DOI · Paper page
- Mangan, 2006, The incoherent feed-forward loop accelerates the response-time of the gal system of Escherichia coli., J. Mol. Biol., 356, 1073, 10.1016/j.jmb.2005.12.003 · DOI · Paper page
- Kaplan, 2008, The incoherent feedforward loop can generate non-monotonic input functions for genes, Mol. Syst. Biol., 4, 203, 10.1038/msb.2008.43 · DOI · Paper page
- Schuster, 2004, Promoter specificity in Pseudomonas aeruginosa quorum sensing revealed by DNA binding of purified LasR, Proc. Natl. Acad. Sci. U. S. A., 101, 15833, 10.1073/pnas.0407229101 · DOI · Paper page
- Rampioni, 2006, The quorum-sensing negative regulator RsaL of Pseudomonas aeruginosa binds to the lasI promoter, J. Bacteriol., 188, 815, 10.1128/JB.188.2.815-819.2006 · DOI
- Rampioni, 2007, RsaL provides quorum sensing homeostasis and functions as a global regulator of gene expression in Pseudomonas aeruginosa, Mol. Microbiol., 66, 1557, 10.1111/j.1365-2958.2007.06029.x · DOI
- Schuster, 2006, A network of networks: quorum-sensing gene regulation in Pseudomonas aeruginosa, Int. J. Med. Microbiol., 296, 73, 10.1016/j.ijmm.2006.01.036 · DOI · Paper page
- Williams, 2009, Quorum sensing and environmental adaptation in Pseudomonas aeruginosa: a tale of regulatory networks and multifunctional signal molecules, Curr. Opin. Microbiol., 12, 182, 10.1016/j.mib.2009.01.005 · DOI · Paper page
- Gilbert, 2009, Global position analysis of the Pseudomonasaeruginosa quorum-sensing transcription factor LasR, Mol. Microbiol., 73, 1072, 10.1111/j.1365-2958.2009.06832.x · DOI · Paper page
- Kang, 2016, Crystal structure of Pseudomonas aeruginosa RsaL bound to promoter DNA reaffirms its role as a global regulator involved in quorum-sensing, Nucleic Acids Res., 45, 699, 10.1093/nar/gkw954 · DOI
- Venturi, 2006, Regulation of quorum sensing in Pseudomonas, FEMS Microbiol. Rev., 30, 274, 10.1111/j.1574-6976.2005.00012.x · DOI · Paper page
- Brown, 2012, Evolution of virulence in opportunistic pathogens: generalism, plasticity, and control, Trends Microbiol., 20, 336, 10.1016/j.tim.2012.04.005 · DOI · Paper page
- Bondí, 2014, Affecting Pseudomonas aeruginosa phenotypic plasticity by quorum sensing dysregulation hampers pathogenicity in murine chronic lung infection, PLoS One, 9, e112105, 10.1371/journal.pone.0112105 · doi:10.1371/journal.pone.0112105
- Basu, 2004, Spatiotemporal control of gene expression with pulse-generating networks, Proc. Natl. Acad. Sci. U. S. A., 101, 6355, 10.1073/pnas.0307571101 · DOI · Paper page
- Ma, 2004, An extended transcriptional regulatory network of Escherichia coli and analysis of its hierarchical structure and network motifs, Nucleic Acids Res., 32, 6643, 10.1093/nar/gkh1009 · DOI · Paper page
- Entus, 2007, Design and implementation of three incoherent feed-forward motif based biological concentration sensors, Syst. Synth. Biol., 1, 119, 10.1007/s11693-007-9008-6 · DOI
- Goentoro, 2009, The incoherent feedforward loop can provide fold-change detection in gene regulation, Mol. Cell, 36, 894, 10.1016/j.molcel.2009.11.018 · DOI · Paper page
- Bleris, 2011, Synthetic incoherent feedforward circuits show adaptation to the amount of their genetic template, Mol. Syst. Biol., 7, 519, 10.1038/msb.2011.49 · DOI · Paper page
- Osella, 2011, The role of incoherent microRNA-mediated feedforward loops in noise buffering, PLoS Comput. Biol., 7, e1001101, 10.1371/journal.pcbi.1001101 · DOI · Paper page
- Rodrigo, 2011, Structural discrimination of robustness in transcriptional feedforward loops for pattern formation, PLoS One, 6, e16904, 10.1371/journal.pone.0016904 · DOI
- Buzi, 2016, Implementation considerations, not topological differences, are the main determinants of noise suppression properties in feedback and incoherent feedforward circuits, PLoS Comput. Biol., 12, e1004958, 10.1371/journal.pcbi.1004958 · doi:10.1371/journal.pcbi.1004958
- Li, 2009, A microRNA imparts robustness against environmental fluctuation during development, Cell, 137, 273, 10.1016/j.cell.2009.01.058 · DOI · Paper page
- Ebert, 2012, Roles for microRNAs in conferring robustness to biological processes, Cell, 149, 515, 10.1016/j.cell.2012.04.005 · DOI · Paper page
- Longo, 2013, A new transcriptional repressor of the Pseudomonas aeruginosa quorum sensing receptor gene lasR, PLoS One, 8, e69554, 10.1371/journal.pone.0069554 · doi:10.1371/journal.pone.0069554
- Albus, 1987, Vfr controls quorum sensing in Pseudomonas aeruginosa, J. Bacteriol., 179, 3928, 10.1128/jb.179.12.3928-3935.1997 · DOI · Paper page
- Simon, 1983, A broad host range mobilization system for in vivo genetic-engineering: transposon mutagenesis in Gram-negative bacteria, Biotechnology, 1, 784, 10.1038/nbt1183-784 · DOI · Paper page
- Sambrook, 1989, Molecular cloning: a laboratory manual
- Figurski, 1979, Replication of an origin-containing derivative of plasmid RK2 dependent on a plasmid function provided in trans, Proc. Natl. Acad. Sci. U. S. A., 76, 1648, 10.1073/pnas.76.4.1648 · DOI · Paper page
- Milton, 1996, Flagellin A is essential for the virulence of Vibrio anguillarum, J. Bacteriol., 178, 1310, 10.1128/jb.178.5.1310-1319.1996 · DOI · Paper page
- Hoang, 1998, A broad host-range Flp-FRT recombination system for site-specific excision of chromosomally located DNA sequences: application for isolation of unmarked Pseudomonas aeruginosa mutants, Gene, 212, 77, 10.1016/S0378-1119(98)00130-9 · DOI · Paper page
- Wilder, 2011, Cooperation and cheating in Pseudomonas aeruginosa: the roles of the lasrhl and pqs quorum-sensing systems, ISME J., 5, 1332, 10.1038/ismej.2011.13 · DOI · Paper page
- Miller, 1972, Experiments in molecular genetics
- Ohman, 1980, Corneal infections in mice with toxin A and elastase mutants of Pseudomonas aeruginosa, J. Infect. Dis., 142, 547, 10.1093/infdis/142.4.547 · DOI
- Kessler, 1982, In vitro inhibition of Pseudomonas aeruginosa elastase by metal-chelating peptide derivatives, Infect. Immun., 38, 716, 10.1128/iai.38.2.716-723.1982 · doi:10.1128/iai.38.2.716-723.1982
- Rampioni, 2009, Contribution of the RsaL global regulator to Pseudomonas aeruginosa virulence and biofilm formation, FEMS Microbiol. Lett., 301, 210, 10.1111/j.1574-6968.2009.01817.x · DOI
- Massai, 2011, A multitask biosensor for micro-volumetric detection of N-3-oxo-dodecanoyl-homoserine lactone quorum sensing signal, Biosens. Bioelectron., 26, 3444, 10.1016/j.bios.2011.01.022 · doi:10.1016/j.bios.2011.01.022
- Kashtan, 2004, Efficient sampling algorithm for estimating subgraph concentrations and detecting network motifs, Bioinformatics, 20, 1746, 10.1093/bioinformatics/bth163 · DOI · Paper page
- Su, 2017, Characterization of the multiple molecular mechanisms underlying RsaL control of phenazine-1-carboxylic acid biosynthesis in the rhizosphere bacterium Pseudomonas aeruginosa PA1201, Mol. Microbiol.
- Ledgham, 2003, Global regulation in Pseudomonas aeruginosa: the regulatory protein AlgR2 (AlgQ) acts as a modulator of quorum sensing, Res. Microbiol., 154, 207, 10.1016/S0923-2508(03)00024-X · doi:10.1016/s0923-2508(03)00024-x
- Schuster, 2003, Identification, timing, and signal specificity of Pseudomonas aeruginosa quorum-controlled genes: a transcriptome analysis, J. Bacteriol., 185, 2066, 10.1128/JB.185.7.2066-2079.2003 · DOI · Paper page
- Hentzer, 2003, Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors, EMBO J., 22, 3803, 10.1093/emboj/cdg366 · DOI · Paper page
- Wagner, 2003, Microarray analysis of Pseudomonas aeruginosa quorum-sensing regulons: effects of growth phase and environment, J. Bacteriol., 185, 2080, 10.1128/JB.185.7.2080-2095.2003 · DOI · Paper page
- Schuster, 2007, Early activation of quorum sensing in Pseudomonas aeruginosa reveals the architecture of a complex regulon, BMC Genomics, 8, 287, 10.1186/1471-2164-8-287 · DOI · Paper page
- Cornforth, 2014, Combinatorial quorum sensing allows bacteria to resolve their social and physical environment, Proc. Natl. Acad. Sci. U. S. A., 111, 4280, 10.1073/pnas.1319175111 · doi:10.1073/pnas.1319175111
- Furukawa, 2006, Keeping their options open: acute versus persistent infections, J. Bacteriol., 188, 1211, 10.1128/JB.188.4.1211-1217.2006 · DOI · Paper page
- Winstanley, 2009, The role of quorum sensing in chronic cystic fibrosis Pseudomonas aeruginosa infections, FEMS Microbiol. Lett., 290, 1, 10.1111/j.1574-6968.2008.01394.x · DOI · Paper page
- Jones, 2010, Activation of the Pseudomonas aeruginosa AlgU regulon through mucA mutation inhibits cyclic AMP/Vfr signaling, J. Bacteriol., 192, 5709, 10.1128/JB.00526-10 · DOI
- Ryall, 2014, The mucoid switch in Pseudomonas aeruginosa represses quorum sensing systems and leads to complex changes to stationary phase virulence factor regulation, PLoS One, 9, e96166, 10.1371/journal.pone.0096166 · doi:10.1371/journal.pone.0096166
- Beatson, 2002, Differential regulation of twitching motility and elastase production by Vfr in Pseudomonasaeruginosa, J. Bacteriol., 184, 3605, 10.1128/JB.184.13.3605-3613.2002 · DOI · Paper page
- Smith, 2004, An adenylate cyclase-controlled signaling network regulates Pseudomonas aeruginosa virulence in a mouse model of acute pneumonia, Infect. Immun., 72, 1677, 10.1128/IAI.72.3.1677-1684.2004 · DOI
- Almblad, 2015, The cyclic AMP-Vfr signaling pathway in Pseudomonas aeruginosa is inhibited by cyclic di-GMP, J. Bacteriol., 197, 2190, 10.1128/JB.00193-15 · DOI · Paper page
- Venturi, 2011, The virtue of temperance: built-in negative regulators of quorum sensing in Pseudomonas, Mol. Microbiol., 82, 1060, 10.1111/j.1365-2958.2011.07890.x · doi:10.1111/j.1365-2958.2011.07890.x
- Rampioni, 2012, Functional characterization of the quorum sensing regulator RsaL in the plant-beneficial strain Pseudomonas putida WCS358, Appl. Environ. Microbiol., 78, 726, 10.1128/AEM.06442-11 · doi:10.1128/aem.06442-11
- Hazan, 2010, Homeostatic interplay between bacterial cell–cell signaling and iron in virulence, PLoS Pathog., 6, e1000810, 10.1371/journal.ppat.1000810 · DOI
- Rampioni, 2010, Transcriptomic analysis reveals a global alkyl-quinolone-independent regulatory role for PqsE in facilitating the environmental adaptation of Pseudomonas aeruginosa to plant and animal hosts, Environ. Microbiol., 12, 1659, 10.1111/j.1462-2920.2010.02214.x · DOI · Paper page
- Rampioni, 2016, Unravelling the genome-wide contributions of specific 2-alkyl-4-quinolones and PqsE to quorum sensing in Pseudomonas aeruginosa, PLoS Pathog., 12, e1006029, 10.1371/journal.ppat.1006029 · DOI · Paper page
Cited by
Pseudomonas aeruginosa: ecology, evolution, pathogenesis and antimicrobial susceptibility
Letizia, M., Diggle, S. P., & Whiteley, M. (2025) · Nature Reviews Microbiology · doi:10.1038/s41579-025-01193-8 · Cited by 231
Metadata
- Authors
- Bondí, R., Longo, F., Messina, M., D'Angelo, F., Visca, P., Leoni, L., & Rampioni, G.
- Venue
- Molecular BioSystems
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-04-20
- Volume
- 13
- Issue
- 6
- Pages
- 1080-1089
- ISSN
- 1742-2051
- 1742-206X
- Cited by
- 21
- References
- 3
- Language
- en
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