Photosensory regulation and signal transduction in bacteria

Challenge: Photosensory gene regulation and signal transduction

CSIC White books: Structural bases of life and evolution of macromolecular complexity (Challenge 2; CSIC white book vol. 2)

PI: S. Padmanabhan

• Diego Bernal Bernal

We study how bacteria sense and respond to light in close collaboration with Prof. Montserrat Elías Arnanz´s group (Dept. Genetics, Univ. of Murcia, Spain). Our primary model is the Gram-negative soil bacterium Myxococcus xanthus. Our findings have also led us to investigate related systems in other bacteria such as other myxobacteria, Thermus thermophilus, Caulobacter crescentus, Bacillus megaterium. Moreover, our work has uncovered proteins that are conserved in multicellular animals from worms (Caenorhabditis elegans) to human, leading us to explore the functions of these proteins in model animal systems and human cell lines. Finally, the links between the light response and other processes in M. xanthus have steered us to studying global regulation, multicellular development, lipid metabolism and CRISPR-Cas systems in this model bacterium. Significant discoveries from our studies include: (a) the vitamin B₁₂-based family of photoreceptors; (b) the long-sought lipid desaturase for plasmalogen biosynthesis conserved in aerobic bacteria and in animals including humans, and a signaling role for plasmalogens; (c) the bacterial RNA polymerase-binding CarD-CdnL family of global regulators and their modes of action; (d) a novel, multifactorial control of the expression of a CRISPR-Cas system. We continue to focus on these in our ongoing work.

In the image, structure of the B₁₂-based photoreceptor CarH bound to DNA (Left), and colonies of the bacterium Myxococcus xanthus (top left and bottom right) in which the lipid desaturase for plasmalogen biosynthesis (CarF) was identified together with HeLa cells showing localization in the endoplasmic reticulum of , TMEM189, the CarF homolog in humans (Right)

Publications

• Gallego-García, …, S. Padmanabhan, M. Elías-Arnanz. "A bacterial light response reveals an orphan desaturase for human plasmalogen synthesis". Science 366: 128-132. DOI: 10.1126/science.aay1436 (2019)  (F1000 Prime recommendation).
• Padmanabhan S, Pérez-Castaño R, Elías-Arnanz M. "B₁₂-based photoreceptors: from structure and function to applications in optogenetics and synthetic biology". Opin. Struct. Biol. 57: 47-55. DOI: 10.1016/j.sbi.2019.01.020 (2019)
• Bernal-Bernal D, Abellón-Ruiz J, Iniesta AA, Pajares-Martínez E, Bastida-Martínez E, Fontes M, Padmanabhan S, Elías-Arnanz M. "Multifactorial control of the expression of a CRISPR-Cas system by an extracytoplasmic function σ/anti-σ pair and a global regulatory complex". Nucleic Acids Res. 46: 6726-6745. DOI:1093/nar/gky475 (2018)
• Padmanabhan S, Jost M, Drennan CL, Elías-Arnanz M. "A new facet of vitamin B₁₂: Gene regulation by cobalamin-based photoreceptors". Annu Rev Biochem. 86: 485-514. DOI:1146/annurev-biochem-061516-044500
• M.Jost, …, S. Padmanabhan,, M. Elías-Arnanz M, C. L. Drennan. "Structural basis for gene regulation by a B₁₂-dependent photoreceptor". Nature 526: 536-541. DOI: 10.1038/nature14950 (2015)[Highlighted in: Sci. Signal. 4: ec131 (2011); Mol Microbiol 91: 635 (2014); Cell163: 1295 (2015); Angew. Chem. 55: 2 (2016)]
• M. Ortiz-Guerrero,…, S. Padmanabhan, M. Elías-Arnanz "Light-dependent gene regulation by a coenzyme B₁₂-based photoreceptor." Proc. Natl. Acad. Sci. USA. 108: 7565-7570. DOI: 10.1073/pnas.1018972108 (2011)[Highlighted in: Sci. Signal. 4: ec131 (2011); Mol Microbiol 91: 635 (2014); Cell163: 1295 (2015); Angew. Chem. 55: 2 (2016)]

Collaborators

• Prof. Montserrat Elias Arnanz´s group (Dept. Genetics, Univ. of Murcia, Spain)
• Prof. Catherine L. Drennan (Depts Chemistry & Biology, MIT and HHMI, USA)
• Dr. Alex Jones (National Physical Laboratory, UK)
• Prof. Modesto Orozco (IRB-Barcelona. Spain)
• Prof. Roseanne J. Sension (University of Michigan)
• Prof. Bernhard Kräutler (University of Innsbruck, Austria).

Financing

• 2019-2021:      PGC2018-094635-B-C22, Plan Nacional I+D+i (MICINN)
• 2016-2018:      BFU2015-67968-C2-2-P, Plan Nacional I+D+i (MINECO)
• 2013-2015:      BFU2012-40184-C02-02, Plan Nacional I+D+i (MINECO)
• 2010-2012:      BFU2009-12445-C02-02. Plan Nacional I+D+i (MICINN)