• PNAS Physics Portal
  • Science Sessions: The PNAS Podcast Program

Assigning chemoreceptors to chemosensory pathways in Pseudomonas aeruginosa

  1. Igor B. Zhulinb,c,3
  1. aDepartment of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125;
  2. bComputational Sciences and Engineering Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831;
  3. cDepartment of Microbiology, University of Tennessee, Knoxville, TN 37996;
  4. dDepartment of Environmental Protection, Estación Experimental del Zaidín, Consejo Superior de Investigaciones Científicas, 18008 Granada, Spain;
  5. eDepartment of Microbiology, University of Washington, Seattle, WA 98195;
  6. fHoward Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125
  1. Edited by Eugene V. Koonin, National Institutes of Health, Bethesda, MD, and approved October 26, 2017 (received for review May 27, 2017)


Multiple receptors transmit information to several signaling pathways that control cellular functions. Which receptor feeds into which pathway and what defines the receptor/pathway specificity are the key questions in cell biology. Here we show that in a model bacterium receptor/pathway specificity is determined by small motifs that can be revealed by comparative sequence analysis of receptor regions that interact with the pathway components. This study provides a path toward computational assignment of receptors to their respective cellular pathways in thousands of bacterial genomes.


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.


  • ?1D.R.O. and A.D.F. contributed equally to this work.

  • ?2Present address: College of Medicine, University of Tennessee Health Sciences Center, Memphis, TN 38163.

  • ?3To whom correspondence should be addressed. Email: ijouline{at}utk.edu.
  • 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 www.danielhellerman.com/lookup/suppl/doi:10.1073/pnas.1708842114/-/DCSupplemental.

Published under the PNAS license.

Online Impact

                                                          1. 956115858 2018-01-22
                                                          2. 730379857 2018-01-22
                                                          3. 346624856 2018-01-22
                                                          4. 201609855 2018-01-22
                                                          5. 72549854 2018-01-21
                                                          6. 795928853 2018-01-21
                                                          7. 752345852 2018-01-21
                                                          8. 566508851 2018-01-21
                                                          9. 615722850 2018-01-21
                                                          10. 689612849 2018-01-21
                                                          11. 846903848 2018-01-21
                                                          12. 674896847 2018-01-21
                                                          13. 11197846 2018-01-21
                                                          14. 986896845 2018-01-21
                                                          15. 667601844 2018-01-21
                                                          16. 385442843 2018-01-21
                                                          17. 496686842 2018-01-21
                                                          18. 915288841 2018-01-21
                                                          19. 885256840 2018-01-21
                                                          20. 726268839 2018-01-21