Signaling via LuxR solos in the insect pathogen Photorhabdus luminescens and the human pathogen Photorhabdus asymbiotica
Final Report Abstract
It is well recognised that bacteria communicate via small diffusible molecules, a process termed quorum sensing. The best understood quorum sensing systems are those that use acylated homoserine lactones (AHLs) for communication. The prototype of those systems consists of a LuxI-like AHL synthase and a cognate LuxR-receptor that senses the signal. However, many proteobacteria possess LuxR receptors that lack any LuxI-type synthase, and thus these receptors are referred to as LuxR orphans or solos. Photorhabdus luminescens is an insect pathogenic bacterium that has a total of 40 LuxR solos, which is one of the highest numbers that has ever been found in bacteria. In this project, we found that one of these LuxR solos, PluR, is part of a novel cell-cell communication system. Instead of AHLs, PluR senses α-pyrones, named photopyrones (PPYs), produced by the pyrone synthase PpyS as signaling molecules. PluR was the first example of a LuxR solo that senses a quorum sensing signal that is not an AHL. The closely related insect and human pathogen Photorhabdus asymbiotica has a close homologue to PluR, named PauR, but lacks LuxI as well as PpyS homologues. We could show that PauR senses dialkylresorcinols (DARs) and their precursors cyclohexanediones (CHDs) instead of PPYs and AHLs as signal. Furthermore, we identified amino acid motifs in the signal-binding domain of PluR and PauR responsible for the specificity of PPY or DAR/CHD sensing, respectively, distinguishing them from the AHL sensors. There is evidence that the evolution from an insect to human pathogen correlated with the evolution of the cell-cell-communication system since putative DAR/CHD signaling is distributed among many human pathogens, while pyrone communication seems to be restricted to invertebrate associating bacteria especially those interacting with insects. Besides LuxR solos that contain a putative AHL binding domain, the majority of the LuxR solos in P. luminescens have a PAS4 domain. We found that the PAS4-LuxR solo Plu2018/Plu2019 is part of a novel type of interkingdom signaling system, as the signal is present in Galleria mellonella insect larvae. In order to identify the chemical nature of this inter-kingdom, we purified the signal from insect homogenate. There is first evidence that the chemical nature of the inter-kingdom-signal is a steroid hormone, putatively ergosterin. As all the LuxR solos that were investigated in this project are involved in pathogenicity and have homologues in diverse human pathogenic bacteria, they represent promising targets for novel antimicrobials.
Publications
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(2013). Oral toxicity of Photorhabdus luminescens and Xenorhabdus nematophila (Enterobacteriaceae) against Aedes aegypti (Diptera: Culicidae). Parasitol. Res., 112(8):2891-2896
da Silva, O.S.; Prado, G.R.; da Silva, J.L.; Silva, C.E.; da Costa, M.; Heermann, R.
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(2013). Pyrones as bacterial signaling molecules, Nat. Chem. Biol., 9(9):573-578
Brachmann, A.O.; Brameyer, S.; Kresovic, D.; Hitkova, I.; Kopp, Y.; Manske, C., Schubert, K.; Bode, H.B.; Heermann, R.
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(2014). LuxR solos in Photorhabdus species. Front. Cell. Infect. Microbiol. 4:166
Brameyer, S.; Kresovic, D.; Bode, H.B.; Heermann, R.
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(2015). Dialkyresorcinols as bacterial signaling molecules. PNAS 112(2):572-7
Brameyer, S.; Kresovic, D.; Bode, H.B.; Heermann, R.
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(2015). Languages and dialects: bacterial communication beyond homoserine lactones. Trends Microbiol. 23(9):521-523
Brameyer, S.; Bode, H.B.; Heermann, R.
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(2015). Specificity of Signal-Binding via Non-AHL LuxR-Type Receptors. PLoS One 10(4):e0124093
Brameyer, S.; Heermann, R.
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(2017). Larvicidal and growth-inhibitory activity of entomopathogenic bacteria culture fluids against Aedes aegypti (Diptera: Culicidae). J. Econ. Entomol. 110(2):378-385
da Silva, J.L.; Undurraga Schwalm, F.; Eugênio Silva, C.; da Costa, M.; Heermann, R.; Santos da Silva, O.
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(2017). Quorum sensing and LuxR solos in Photorhabdus. Curr. Top. Microbiol. Immunol. 402:103-119
Brameyer, S.; Heermann, R.
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(2018). Entomopathogenic bacteria Photorhabdus luminescens as drug source against Leishmania amazonensis. Parasitology 145(8):1065-1074
Antonello, A.M.; Sartori, T.; Folmer Correa, A.P.; Brandelli, A.; Heermann, R.; Rodrigues Júnior, L.C.; Peres, A.; Romão, P.R.T.; Da Silva, O.S.
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(2019). Anti-Trypanosoma activity of bioactive metabolites from Photorhabdus luminescens and Xenorhabdus nematophila. Exp. Parasitol.
Antonello, A.M., Sartori, T.; Brasil da Silva, M.; Prophiro, J.S.; Pinge-Filho, P.; Heermann, R.; Santos da Silva, O.; Torres Romão, P.R.
