title: Alarmone (p)ppGpp regulates the transition from pathogenicity to mutualism in Photorhabdus luminescens.
abstract: The enteric gamma-proteobacterium Photorhabdus luminescens kills a wide range of insects, whilst also maintaining a mutualistic relationship with soil nematodes from the family Heterorhabditis. Pathogenicity is associated with bacterial exponential growth, whilst mutualism is associated with post-exponential (stationary) phase. During post-exponential growth, P. luminescens also elaborates an extensive secondary metabolism, including production of bioluminescence, antibiotics and pigment. However, the regulatory network that controls the expression of this secondary metabolism is not well understood. The stringent response is a well-described global regulatory system in bacteria and mediated by the alarmone (p)ppGpp. In this study, we disrupted the genes relA and spoT, encoding the two predicted (p)ppGpp synthases of P. luminescens TTO1, and we showed that (p)ppGpp is required for secondary metabolism. Moreover, we found the (p)ppGpp is not required for pathogenicity of P. luminescens, but is required for bacterial survival within the insect cadaver. Finally, we showed that (p)ppGpp is required for P. luminescens to support normal nematode growth and development. Therefore, the regulatory network that controls the transition from pathogenicity to mutualism in P. luminescens requires (p)ppGpp. This is the first report outlining a role for (p)ppGpp in controlling the outcome of an interaction between a bacteria and its host.
authors: Department of Biology, University of Copenhagen, DK-2200, Copenhagen, Denmark.|School of Microbiology and APC Microbiome Institute, University College Cork, Cork, Ireland.
authors: Ragnhild
authors: R
authors: Bager
authors: Department of Biology, University of Copenhagen, DK-2200, Copenhagen, Denmark.
authors: Mohammad
authors: M
authors: Roghanian
authors: Department of Biology, University of Copenhagen, DK-2200, Copenhagen, Denmark.
authors: Kenn
authors: K
authors: Gerdes
authors: School of Microbiology and APC Microbiome Institute, University College Cork, Cork, Ireland.
authors: David J
authors: DJ
authors: Clarke
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000096:biosynthesis; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006158:Guanosine Pentaphosphate / Q000378:metabolism*; D008025:Ligases / Q000235:genetics; D009036:Moths / Q000382:microbiology* / Q000502:physiology; D020637:Photorhabdus / Q000235:genetics / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D017172:Rhabditoidea / Q000254:growth & development / Q000382:microbiology*; D064210:Secondary Metabolism; D013559:Symbiosis; D014774:Virulence
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D006158:Guanosine Pentaphosphate; D008025:Ligases; C028812:guanosine 3',5'-polyphosphate synthetases