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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

Bondí, Roslen, Longo, Francesca, Messina, Marco, D'Angelo, Francesca, Visca, Paolo, Leoni, Livia, Rampioni, Giordano·2017·Molecular BioSystems

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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Metadata

Authors
Bondí, R., Longo, F., Messina, M., D'Angelo, F., Visca, P., Leoni, L., & Rampioni, G.
Venue
Molecular BioSystems
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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Bondí, R., Longo, F., Messina, M., D'Angelo, F., Visca, P., Leoni, L., & Rampioni, G. (2017). 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. Molecular BioSystems. https://doi.org/10.1039/c7mb00040e

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