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Unlimited multistability and Boolean logic in microbial signalling
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Kothamachu, Varun B., Feliu, Elisenda, Cardelli, Luca and Soyer, Orkun S. (2015) Unlimited multistability and Boolean logic in microbial signalling. Journal of The Royal Society Interface, Volume 12 (Number 108). pp. 1-9. Article number 20150234. doi:10.1098/rsif.2015.0234 ISSN 1742-5689.
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Official URL: http://dx.doi.org/10.1098/rsif.2015.0234
Abstract
The ability to map environmental signals onto distinct internal physiological states or programmes is critical for single-celled microbes. A crucial systems dynamics feature underpinning such ability is multistability. While unlimited multistability is known to arise from multi-site phosphorylation seen in the signalling networks of eukaryotic cells, a similarly universal mechanism has not been identified in microbial signalling systems. These systems are generally known as two-component systems comprising histidine kinase (HK) receptors and response regulator proteins engaging in phosphotransfer reactions. We develop a mathematical framework for analysing microbial systems with multi-domain HK receptors known as hybrid and unorthodox HKs. We show that these systems embed a simple core network that exhibits multistability, thereby unveiling a novel biochemical mechanism for multistability. We further prove that sharing of downstream components allows a system with n multi-domain hybrid HKs to attain 3n steady states. We find that such systems, when sensing distinct signals, can readily implement Boolean logic functions on these signals. Using two experimentally studied examples of two-component systems implementing hybrid HKs, we show that bistability and implementation of logic functions are possible under biologically feasible reaction rates. Furthermore, we show that all sequenced microbial genomes contain significant numbers of hybrid and unorthodox HKs, and some genomes have a larger fraction of these proteins compared with regular HKs. Microbial cells are thus theoretically unbounded in mapping distinct environmental signals onto distinct physiological states and perform complex computations on them. These findings facilitate the understanding of natural two-component systems and allow their engineering through synthetic biology.
Item Type: | Journal Article | ||||||||
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Subjects: | Q Science > QR Microbiology | ||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||
Library of Congress Subject Headings (LCSH): | Prokaryotes, Cellular signal transduction -- Mathematical models | ||||||||
Journal or Publication Title: | Journal of The Royal Society Interface | ||||||||
Publisher: | The Royal Society Publishing | ||||||||
ISSN: | 1742-5689 | ||||||||
Official Date: | July 2015 | ||||||||
Dates: |
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Volume: | Volume 12 | ||||||||
Number: | Number 108 | ||||||||
Number of Pages: | 9 | ||||||||
Page Range: | pp. 1-9 | ||||||||
Article Number: | Article number 20150234 | ||||||||
DOI: | 10.1098/rsif.2015.0234 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||
Date of first compliant deposit: | 29 December 2015 | ||||||||
Date of first compliant Open Access: | 29 December 2015 | ||||||||
Funder: | Spain. Ministerio de EconomÃa y Competitividad, Comissionat per Universitats i Recerca de la Generalitat de Catalunya (CURGC), Engineering and Physical Sciences Research Council (EPSRC), Microsoft Research | ||||||||
Grant number: | MTM2012-38122-C03-01/FEDER (MEC) |
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