A defense-offense multi-layered regulatory switch in a pathogenic bacterium

Mor Nitzan, Pierre Fechter, Asaf Peer, Yael Altuvia, Delphine Bronesky, François Vandenesch, Pascale Romby, Ofer Biham, Hanah Margalit*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Cells adapt to environmental changes by efficiently adjusting gene expression programs. Staphylococcus aureus, an opportunistic pathogenic bacterium, switches between defensive and offensive modes in response to quorum sensing signal. We identified and studied the structural characteristics and dynamic properties of the core regulatory circuit governing this switch by deterministic and stochastic computational methods, as well as experimentally. This module, termed here Double Selector Switch (DSS), comprises the RNA regulator RNAIII and the transcription factor Rot, defining a double-layered switch involving both transcriptional and post-transcriptional regulations. It coordinates the inverse expression of two sets of target genes, immuno-modulators and exotoxins, expressed during the defensive and offensive modes, respectively. Our computational and experimental analyses show that the DSS guarantees fine-tuned coordination of the inverse expression of its two gene sets, tight regulation, and filtering of noisy signals. We also identified variants of this circuit in other bacterial systems, suggesting it is used as a molecular switch in various cellular contexts and offering its use as a template for an effective switching device in synthetic biology studies.

Original languageAmerican English
Pages (from-to)1357-1369
Number of pages13
JournalNucleic Acids Research
Volume43
Issue number3
DOIs
StatePublished - 18 Feb 2015

Bibliographical note

Funding Information:
We thank M. Ryckelynck, P. Dumas, E. Westhof, L. Arga-man, S. Melamed and R. Feigenbaum for helpful discussions. MN is grateful to the Azrieli Foundation for the award of an Azrieli Fellowship. We thank our team members for valuable discussions. We are grateful to Dr Frees (Faculty of Life Sciences, Copenhagen, Denmark) for providing us the antibodies against Rot.

Funding Information:
High Council for Scientific and Technological cooperation between France–Israel (to H.M., O.B. and P.R.); the I-CORE Programs of the Planning and Budgeting Committee and The Israel Science Foundation (41/11, 1796/12 to H.M.); Centre National de la Recherche Scientifique and from a funding from the state managed by the FrenchNa-tional Research Agency as part of the Investments for the future program under the framework of the LABEX:ANR-10-LABX-0036 NETRNA (to P.R.). Funding for open access charge: The I-CORE Program of the Planning and Budgeting Committee and The Israel Science Foundation (41/11 to H.M.). Conflict of interest statement. None declared.

Publisher Copyright:
© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

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