title: An antimicrobial peptide-resistant minor subpopulation of Photorhabdus luminescens is responsible for virulence.
abstract: Some of the bacterial cells in isogenic populations behave differently from others. We describe here how a new type of phenotypic heterogeneity relating to resistance to cationic antimicrobial peptides (CAMPs) is determinant for the pathogenic infection process of the entomopathogenic bacterium Photorhabdus luminescens. We demonstrate that the resistant subpopulation, which accounts for only 0.5% of the wild-type population, causes septicemia in insects. Bacterial heterogeneity is driven by the PhoPQ two-component regulatory system and expression of pbgPE, an operon encoding proteins involved in lipopolysaccharide (LPS) modifications. We also report the characterization of a core regulon controlled by the DNA-binding PhoP protein, which governs virulence in P. luminescens. Comparative RNAseq analysis revealed an upregulation of marker genes for resistance, virulence and bacterial antagonism in the pre-existing resistant subpopulation, suggesting a greater ability to infect insect prey and to survive in cadavers. Finally, we suggest that the infection process of P. luminescens is based on a bet-hedging strategy to cope with the diverse environmental conditions experienced during the lifecycle.
authors.affiliation: DGIMI, INRA, Univ. Montpellier, Montpellier, France.
authors.forename: Annabelle
authors.initials: A
authors.lastname: Mouammine
authors.affiliation: DGIMI, INRA, Univ. Montpellier, Montpellier, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Pages
authors.affiliation: DGIMI, INRA, Univ. Montpellier, Montpellier, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Lanois
authors.affiliation: DGIMI, INRA, Univ. Montpellier, Montpellier, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Gaudriault
authors.affiliation: INRA, UR454 Microbiologie, Saint-Genès-Champanelle, France.
authors.forename: Gregory
authors.initials: G
authors.lastname: Jubelin
authors.affiliation: MGX-Montpellier GenomiX, c/o IGF, Montpellier, France.
authors.forename: Maurine
authors.initials: M
authors.lastname: Bonabaud
authors.affiliation: Laboratoire d'Analyse Bioinformatique en Génomique et Métabolisme, CEA, Genoscope &CNRS, Evry, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Cruveiller
authors.affiliation: MGX-Montpellier GenomiX, c/o IGF, Montpellier, France.
authors.forename: Emeric
authors.initials: E
authors.lastname: Dubois
authors.affiliation: Laboratoire d'Analyse Bioinformatique en Génomique et Métabolisme, CEA, Genoscope &CNRS, Evry, France.
authors.forename: David
authors.initials: D
authors.lastname: Roche
authors.affiliation: LIPM, INRA, CNRS, Castanet-Tolosan, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Legrand
authors.affiliation: DGIMI, INRA, Univ. Montpellier, Montpellier, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Brillard
authors.affiliation: DGIMI, INRA, Univ. Montpellier, Montpellier, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Givaudan
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D052978:Disk Diffusion Antimicrobial Tests; D024881:Drug Resistance, Bacterial; D004756:Enterobacteriaceae Infections / Q000382:microbiology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D023061:Gene Order; D005798:Genes, Bacterial; D007313:Insecta / Q000382:microbiology; D009154:Mutation; D009876:Operon; D020637:Photorhabdus / Q000187:drug effects* / Q000235:genetics* / Q000472:pathogenicity; D014774:Virulence / Q000235:genetics
chemical_list: D023181:Antimicrobial Cationic Peptides