Signaling via LuxR solos in the insect pathogen Photorhabdus luminescens and the human pathogen Photorhabdus asymbiotica

• Applicant: Professor Dr. Ralf Heermann
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms
• Term: from 2010 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 190135878

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 yet 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 39 LuxR solos, which is one of the highest numbers that has ever been found in bacteria. In the previous funding period we found that one of these LuxR solos, PluR, is part of a novel cell-cell communication system. Instead of AHLs, PluR senses alpha-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 have first evidence that PauR senses dialkylresorcinols (DARs) and their precursors cyclohexanediones (CHDs) instead of PPYs and AHLs as signal. In this project we will therefore investigate this novel DAR/CHD-based cell-cell communication system in the native host P. asymbiotica. Moreover, we will attempt to identify amino acid motifs in the signal-binding domain of PluR and PauR that make them specific PPY or DAR/CHD sensors, respectively, and that distinguish them from the AHL sensors. Additionally, we will investigate the DNA-binding site(s) of PluR and PauR to define a specific DNA-binding box of these LuxR solos. Besides LuxR solos that contain a putative AHL binding domain, the majority of the LuxR solos in P. luminescens have a PAS4 domain. We know that the PAS4-LuxR solo Plu2018/Plu2019 is part of a novel type of inter-kingdom signaling system, as the signal is present in the insect Galleria mellonella. We therefore aim to identify the chemical nature of this inter-kingdom signal in the current project proposal. As all the LuxR solos that are investigated in this project are involved in pathogenicity and have homologues in diverse human pathogenic bacteria, they might act as targets for novel antimicrobials in the future.

• DFG Programme: Research Grants