title: New insights into how Yersinia pestis adapts to its mammalian host during bubonic plague.
abstract: Bubonic plague (a fatal, flea-transmitted disease) remains an international public health concern. Although our understanding of the pathogenesis of bubonic plague has improved significantly over the last few decades, researchers have still not been able to define the complete set of Y. pestis genes needed for disease or to characterize the mechanisms that enable infection. Here, we generated a library of Y. pestis mutants, each lacking one or more of the genes previously identified as being up-regulated in vivo. We then screened the library for attenuated virulence in rodent models of bubonic plague. Importantly, we tested mutants both individually and using a novel, "per-pool" screening method that we have developed. Our data showed that in addition to genes involved in physiological adaptation and resistance to the stress generated by the host, several previously uncharacterized genes are required for virulence. One of these genes (ympt1.66c, which encodes a putative helicase) has been acquired by horizontal gene transfer. Deletion of ympt1.66c reduced Y. pestis' ability to spread to the lymph nodes draining the dermal inoculation site--probably because loss of this gene decreased the bacteria's ability to survive inside macrophages. Our results suggest that (i) intracellular survival during the early stage of infection is important for plague and (ii) horizontal gene transfer was crucial in the acquisition of this ability.
authors.affiliation: Equipe Peste et Yersinia pestis; INSERM U1019, Lille, France; Centre National de la Recherche Scientifique UMR8204, Lille, France; Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, Lille, France; Univ Lille Nord de France, Lille, France; UDSL, Centre d'Infection et d'Immunité de Lille, Lille, France.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Pradel
authors.affiliation: Equipe Peste et Yersinia pestis; INSERM U1019, Lille, France; Centre National de la Recherche Scientifique UMR8204, Lille, France; Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, Lille, France; Univ Lille Nord de France, Lille, France; UDSL, Centre d'Infection et d'Immunité de Lille, Lille, France; CHU Lille, Lille, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Lemaître
authors.affiliation: Equipe Peste et Yersinia pestis; INSERM U1019, Lille, France; Centre National de la Recherche Scientifique UMR8204, Lille, France; Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, Lille, France; Univ Lille Nord de France, Lille, France; UDSL, Centre d'Infection et d'Immunité de Lille, Lille, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Merchez
authors.affiliation: Equipe Peste et Yersinia pestis; INSERM U1019, Lille, France; Centre National de la Recherche Scientifique UMR8204, Lille, France; Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, Lille, France; Univ Lille Nord de France, Lille, France; UDSL, Centre d'Infection et d'Immunité de Lille, Lille, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ricard
authors.affiliation: Equipe Peste et Yersinia pestis; INSERM U1019, Lille, France; Centre National de la Recherche Scientifique UMR8204, Lille, France; Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, Lille, France; Univ Lille Nord de France, Lille, France; UDSL, Centre d'Infection et d'Immunité de Lille, Lille, France.
authors.forename: Angéline
authors.initials: A
authors.lastname: Reboul
authors.affiliation: Equipe Peste et Yersinia pestis; INSERM U1019, Lille, France; Centre National de la Recherche Scientifique UMR8204, Lille, France; Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, Lille, France; Univ Lille Nord de France, Lille, France; UDSL, Centre d'Infection et d'Immunité de Lille, Lille, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Dewitte
authors.affiliation: Equipe Peste et Yersinia pestis; INSERM U1019, Lille, France; Centre National de la Recherche Scientifique UMR8204, Lille, France; Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, Lille, France; Univ Lille Nord de France, Lille, France; UDSL, Centre d'Infection et d'Immunité de Lille, Lille, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Sebbane
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006790:Host-Parasite Interactions / Q000235:genetics*; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D010930:Plague / Q000235:genetics*; D051381:Rats; D014774:Virulence; D015010:Yersinia pestis / Q000235:genetics* / Q000472:pathogenicity*