The regulation of symbiosis in Photorhabdus

Speaker: Prof. David Clarke, School of Microbiology and APC Microbiome Institute, University College Cork, Ireland
Host: Prof. Kenn Gerdes, Centre for Bacterial Stress Response and Persistence

Abstract
Photorhabdus is a genus of bioluminescent, Gram-negative bacterium that is highly virulent to insect larvae whilst, at the same time, maintaining a mutualistic relationship with nematodes of the family Heterorhabditiae. Therefore Photorhabdus is distinguished from other bacteria by its requirement to be both a pathogen and a mutualist of 2 different invertebrate hosts. Photorhabdus elaborates an extensive secondary metabolism that is associated with the mutualistic association between the bacteria and the nematode. Amongst the secondary metabolites produced by Photorhabdus is a novel antibiotic called 3-5-dihydroxy-4-isopropylstilbene (ST). ST is a stilbene, an important class of bioactive molecule that is normally produced by plants. Indeed Photorhabdus is the only non-plant organism known to produce a stilbene. We have characterized the novel ST-biosynthetic pathway in Photorhabdus and we have shown that ST is a multi-potent molecule with roles in both pathogenicity and mutualism. We have also identified a number of genes that are involved in the regulation of secondary metabolism in Photorhabdus including mdh (encoding malate dehydrogenase, a key enzyme in the TCA cycle). Further in vivo studies have confirmed that the TCA cycle is also required for the transition of Photorhabdus from pathogen to mutualist. Therefore there appears to be a metabolic switch that controls the transition from pathogenicity to mutualism (and from primary to secondary metabolism) in Photorhabdus. The nature of this metabolic switch remains a focus of our research and we have recently initiated both transcriptomic and metabolomic studies in order to try to fully characterize the physiological changes that occur in Photorhabdus as a consequence of this metabolic switch