A metabolic switch is involved in lifestyle decisions in Photorhabdus luminescens

Photorhabdus luminescens is a species of Gram-negative bacteria that is pathogenic to insects while also maintaining a mutualistic association with nematodes from the family Heterorhabditis. P. luminescens elaborates an extensive secondary metabolism during the post-exponential phase of growth that includes the production of an antibiotic called 3-5-dihydroxy-4-isopropylstilbene (ST), an anthraquinone pigment (AQ) and bioluminescence. In this study we identified a mutant that was unable to produce ST, AQ and light. This mutation was found to be in the mdh gene, encoding malate dehydrogenase, a key enzyme in the tricarboxylic acid (TCA) cycle. Interestingly the mdh mutant was unaffected in virulence but was unable to support nematode growth and development in vivo or in vitro. This clearly establishes that secondary metabolism in P. luminescens is required for the mutualistic interaction with the nematode. Furthermore, the construction of mutations in key genes in other central metabolic pathways confirmed the critical role for the TCA cycle in both secondary metabolism and mutualism, but not in virulence. Therefore, we conclude that the TCA cycle is required for the transition of P. luminescens from pathogen to mutualist implicating the involvement of a metabolic switch in the regulation of lifestyle decisions in this bacterium.