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Assigning chemoreceptors to chemosensory pathways in Pseudomonas aeruginosa

Ortega, Davi R. and Fleetwood, Aaron D. and Krell, Tino and Harwood, Caroline S. and Jensen, Grant J. and Zhulin, Igor B. (2017) Assigning chemoreceptors to chemosensory pathways in Pseudomonas aeruginosa. Proceedings of the National Academy of Sciences of the United States of America, 114 (48). pp. 12809-12814. ISSN 0027-8424. PMCID PMC5715753. doi:10.1073/pnas.1708842114.

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In contrast to Escherichia coli, a model organism for chemotaxis that has 5 chemoreceptors and a single chemosensory pathway, Pseudomonas aeruginosa PAO1 has a much more complex chemosensory network, which consists of 26 chemoreceptors feeding into four chemosensory pathways. While several chemoreceptors were rigorously linked to specific pathways in a series of experimental studies, for most of them this information is not available. Thus, we addressed the problem computationally. Protein–protein interaction network prediction, coexpression data mining, and phylogenetic profiling all produced incomplete and uncertain assignments of chemoreceptors to pathways. However, comparative sequence analysis specifically targeting chemoreceptor regions involved in pathway interactions revealed conserved sequence patterns that enabled us to unambiguously link all 26 chemoreceptors to four pathways. Placing computational evidence in the context of experimental data allowed us to conclude that three chemosensory pathways in P. aeruginosa utilize one chemoreceptor per pathway, whereas the fourth pathway, which is the main system controlling chemotaxis, utilizes the other 23 chemoreceptors. Our results show that while only a very few amino acid positions in receptors, kinases, and adaptors determine their pathway specificity, assigning receptors to pathways computationally is possible. This requires substantial knowledge about interacting partners on a molecular level and focusing comparative sequence analysis on the pathway-specific regions. This general principle should be applicable to resolving many other receptor–pathway interactions.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle Information
Ortega, Davi R.0000-0002-8344-2335
Jensen, Grant J.0000-0003-1556-4864
Zhulin, Igor B.0000-0002-6708-5323
Additional Information:© 2017 National Academy of Sciences. Edited by Eugene V. Koonin, National Institutes of Health, Bethesda, MD, and approved October 26, 2017 (received for review May 27, 2017). Published online before print November 13, 2017. We thank Jacob Pollack for technical assistance and Ariane Briegel for helpful discussions. This work was supported in part by National Institutes of Health Grants GM072295 (to I.B.Z.) and GM122588 (to G.J.J.). D.R.O. and A.D.F. contributed equally to this work. Author contributions: D.R.O., A.D.F., and I.B.Z. designed research; D.R.O. and A.D.F. performed research; D.R.O. contributed new reagents/analytic tools; D.R.O., A.D.F., T.K., C.S.H., G.J.J., and I.B.Z. analyzed data; and D.R.O., A.D.F., T.K., C.S.H., G.J.J., and I.B.Z. wrote the paper. The authors declare no conflict of interest. This article is a PNAS Direct Submission. This article contains supporting information online at Published under the PNAS license.
Funding AgencyGrant Number
Subject Keywords:signal transduction; protein–protein interactions; chemotaxis; computational prediction
Issue or Number:48
PubMed Central ID:PMC5715753
Record Number:CaltechAUTHORS:20171114-080129120
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Official Citation:Davi R. Ortega, Aaron D. Fleetwood, Tino Krell, Caroline S. Harwood, Grant J. Jensen, and Igor B. Zhulin Assigning chemoreceptors to chemosensory pathways in Pseudomonas aeruginosa PNAS 2017 114 (48) 12809-12814; published ahead of print November 13, 2017, doi:10.1073/pnas.1708842114
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:83185
Deposited By: Tony Diaz
Deposited On:14 Nov 2017 17:12
Last Modified:21 Mar 2022 17:10

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