Bacterial Infection Biology
The increasing number of antibiotic resistances in pathogenic bacteria enhances the urgent need for alternative antimicrobials. We discover and investigate novel cell-cell communication systems in bacteria as putative target of new antimicrobial drugs. Therefore, we use the enteric insect pathogenic bacterium Photorhabdus luminescens and the human pathogen Photorhabdus asymbiotica as model organisms. It is well known that bacteria communicate via small diffusible molecules to mediate group-coordinated, e.g. pathogenic, behavior, a process termed quorum sensing. The prototypical quorum sensing system of Gram-negative bacteria consists of a LuxI-type autoinducer synthase that produces acyl-homoserine lactones (AHLs) as signals, and a LuxR-type receptor that detects the AHLs to control expression of specific genes. However, many bacteria possess LuxR homologs but lack a cognate LuxI-type AHL synthase. Those LuxR-type receptors are designated as LuxR orphans or solos. Entomopathogenic bacteria of the genus Photorhabdus all harbor an exceptionally high number of LuxR solos. By analyzing the function of these receptors in cooperation with the group of Prof. Dr. Helge Bode (Goethe-Universität Frankfurt am Main), we have already identified two novel types of quorum sensing systems in these bacteria that use molecules different from AHLs for communication. P. luminescens uses photopyrones and P. asymbiotica uses dialkylresorcinols as communication molecules. The corresponding quorum sensing systems PpyS/PluR and DarABC/PauR, respectively, are both involved in regulation of pathogenicity. Since homologs of these systems are found in other (human) pathogens as well, we screen for inhibitors of these kinds of bacterial cell-cell communication systems as potential novel antimicrobial drugs.
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