title: Bacteriophage predation promotes serovar diversification in Listeria monocytogenes.
abstract: Listeria monocytogenes is a bacterial pathogen classified into distinct serovars (SVs) based on somatic and flagellar antigens. To correlate phenotype with genetic variation, we analyzed the wall teichoic acid (WTA) glycosylation genes of SV 1/2, 3 and 7 strains, which differ in decoration of the ribitol-phosphate backbone with N-acetylglucosamine (GlcNAc) and/or rhamnose. Inactivation of lmo1080 or the dTDP-l-rhamnose biosynthesis genes rmlACBD (lmo1081-1084) resulted in loss of rhamnose, whereas disruption of lmo1079 led to GlcNAc deficiency. We found that all SV 3 and 7 strains actually originate from a SV 1/2 background, as a result of small mutations in WTA rhamnosylation and/or GlcNAcylation genes. Genetic complementation of different SV 3 and 7 isolates using intact alleles fully restored a characteristic SV 1/2 WTA carbohydrate pattern, including antisera reactions and phage adsorption. Intriguingly, phage-resistant L. monocytogenes EGDe (SV 1/2a) isolates featured the same glycosylation gene mutations and were serotyped as SV 3 or 7 respectively. Again, genetic complementation restored both carbohydrate antigens and phage susceptibility. Taken together, our data demonstrate that L. monocytogenes SV 3 and 7 originate from point mutations in glycosylation genes, and we show that phage predation represents a major driving force for serovar diversification and evolution of L. monocytogenes.
authors.affiliation: Institute of Food, Nutrition and Health, ETH Zurich, CH-8092, Zurich, Switzerland.
authors.forename: Marcel R
authors.initials: MR
authors.lastname: Eugster
authors.affiliation: Institute of Food, Nutrition and Health, ETH Zurich, CH-8092, Zurich, Switzerland.
authors.forename: Laurent S
authors.initials: LS
authors.lastname: Morax
authors.affiliation: Institute of Food, Nutrition and Health, ETH Zurich, CH-8092, Zurich, Switzerland.
authors.forename: Vanessa J
authors.initials: VJ
authors.lastname: Hüls
authors.affiliation: Institute of Food, Nutrition and Health, ETH Zurich, CH-8092, Zurich, Switzerland.
authors.forename: Simona G
authors.initials: SG
authors.lastname: Huwiler
authors.affiliation: Institut Pasteur, French National Reference Center and WHO Collaborating Center for Listeria, 75015, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Leclercq
authors.affiliation: Institut Pasteur, French National Reference Center and WHO Collaborating Center for Listeria, 75015, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Lecuit
authors.affiliation: Institute of Food, Nutrition and Health, ETH Zurich, CH-8092, Zurich, Switzerland.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Loessner
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism; D001435:Bacteriophages / Q000235:genetics / Q000502:physiology*; D002473:Cell Wall / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D005816:Genetic Complementation Test; D014644:Genetic Variation; D006031:Glycosylation; D008089:Listeria monocytogenes / Q000145:classification* / Q000235:genetics / Q000821:virology*; D008969:Molecular Sequence Data; D009702:Nucleoside Diphosphate Sugars / Q000235:genetics; D010641:Phenotype; D017354:Point Mutation; D012210:Rhamnose / Q000378:metabolism; D065288:Serogroup; D012703:Serotyping; D013682:Teichoic Acids / Q000235:genetics* / Q000378:metabolism; D013942:Thymine Nucleotides / Q000235:genetics
chemical_list: D009702:Nucleoside Diphosphate Sugars; D013682:Teichoic Acids; D013942:Thymine Nucleotides; C073293:thymidine diphosphate rhamnose; D012210:Rhamnose; D000117:Acetylglucosamine