The PhoP-PhoQ Two-Component Regulatory System of Photorhabdus luminescens Is Essential for Virulence in Insects

Abstract

Photorhabdus luminescens is a symbiont of entomopathogenic nematodes. Analysis of the genome sequence of this organism revealed a homologue of PhoP-PhoQ, a two-component system associated with virulence in intracellular bacterial pathogens. This organism was shown to respond to the availability of environmental magnesium. A mutant with a knockout mutation in the regulatory component of this system (phoP) had no obvious growth defect. It was, however, more motile and more sensitive to antimicrobial peptides than its wild-type parent. Remarkably, the mutation eliminated virulence in an insect model. No insect mortality was observed after injection of a large number of the phoP bacteria, while very small amounts of parental cells killed insect larvae in less than 48 h. At the molecular level, the PhoPQ system mediated Mg 2؉ -dependent modifications in lipopolysaccharides and controlled a locus (pbgPE) required for incorporation of 4-aminoarabinose into lipid A. Mg 2؉ -regulated gene expression of pbgP1 was absent in the mutant and was restored when phoPQ was complemented in trans. This finding highlights the essential role played by PhoPQ in the virulence of an entomopathogen.

The pmrF polymyxin-resistance operon of Yersinia pseudotuberculosis is upregulated by the PhoP-PhoQ two-component system but not by PmrA-PmrB, and is not required for virulence

“…In the pathogenic yersiniae, the pmrF operon is inserted between the btuCDE operon (required for the passage of vitamin B 12 through the outer and inner bacterial membranes (de Veaux et al, 1986) and the nplC gene (encoding a putative lipoprotein of unknown function). An identical genetic organization was described very recently in the insect pathogen Photorhabdus luminescens (Derzelle et al, 2004). In contrast, btu and nplC homologue genes are clustered on the Salmonella chromosome, at some distance (985 kb) from the pmrF operon.…”

“…A lack of conserved motifs in these promoting regions has also been observed in Ph. luminescens (Derzelle et al, 2004).…”

Genomic basis of endosymbiont-conferred protection against an insect parasitoid

“…This two-component system controls expression of the pbgPE operon in Photorhabdus luminescens and is associated with virulence against insects; pbgPE mutants are lacking an O-antigen, resulting in increased sensitivity to insect-produced antimicrobial peptides and acidic pH (Derzelle et al 2004;Bennett and Clarke 2005).…”

Bacterial strategies to overcome insect defences

“…Global regulators play an important role in virulence towards insects: the GacS/GacA two-component system controls the P. entomophila infectious process 50 , PhoP/PhoQ is the master regulator of virulence in P. luminescens 72 , Lrp regulates both mutualism and pathogenicity in Xenorhabus 73 and PlcR activates the transcription of genes required for virulence in B. thuringiensis 74,75 . Another striking example is found in E. c. carotovora 15, where the evf gene is under the control of Hor, a regulator of genes that are involved in plant pathogenesis 36 .…”