title: Novel plasmids and resistance phenotypes in Yersinia pestis: unique plasmid inventory of strain Java 9 mediates high levels of arsenic resistance.
abstract: Growing evidence suggests that the plasmid repertoire of Yersinia pestis is not restricted to the three classical virulence plasmids. The Java 9 strain of Y. pestis is a biovar Orientalis isolate obtained from a rat in Indonesia. Although it lacks the Y. pestis-specific plasmid pMT, which encodes the F1 capsule, it retains virulence in mouse and non-human primate animal models. While comparing diverse Y. pestis strains using subtractive hybridization, we identified sequences in Java 9 that were homologous to a Y. enterocolitica strain carrying the transposon Tn2502, which is known to encode arsenic resistance. Here we demonstrate that Java 9 exhibits high levels of arsenic and arsenite resistance mediated by a novel promiscuous class II transposon, named Tn2503. Arsenic resistance was self-transmissible from Java 9 to other Y. pestis strains via conjugation. Genomic analysis of the atypical plasmid inventory of Java 9 identified pCD and pPCP plasmids of atypical size and two previously uncharacterized cryptic plasmids. Unlike the Tn2502-mediated arsenic resistance encoded on the Y. enterocolitica virulence plasmid; the resistance loci in Java 9 are found on all four indigenous plasmids, including the two novel cryptic plasmids. This unique mobilome introduces more than 105 genes into the species gene pool. The majority of these are encoded by the two entirely novel self-transmissible plasmids, which show partial homology and synteny to other enterics. In contrast to the reductive evolution in Y. pestis, this study underlines the major impact of a dynamic mobilome and lateral acquisition in the genome evolution of the plague bacterium.
authors.affiliation: Institute for Genome Sciences and Department of Microbiology and Immunology, University of Maryland, School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Mark
authors.initials: M
authors.lastname: Eppinger
authors.forename: Lyndsay
authors.initials: L
authors.lastname: Radnedge
authors.forename: Gary
authors.initials: G
authors.lastname: Andersen
authors.forename: Nicholas
authors.initials: N
authors.lastname: Vietri
authors.forename: Grant
authors.initials: G
authors.lastname: Severson
authors.forename: Sherry
authors.initials: S
authors.lastname: Mou
authors.forename: Jacques
authors.initials: J
authors.lastname: Ravel
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Worsham
mesh_terms: D000818:Animals; D001151:Arsenic / Q000494:pharmacology; D018053:Arsenites / Q000494:pharmacology; D003227:Conjugation, Genetic; D004251:DNA Transposable Elements / Q000235:genetics*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005798:Genes, Bacterial / Q000235:genetics; D051379:Mice; D016254:Mutagenesis, Insertional; D010641:Phenotype; D010930:Plague / Q000382:microbiology; D010957:Plasmids / Q000235:genetics*; D051381:Rats; D014774:Virulence / Q000235:genetics; D015010:Yersinia pestis / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity
chemical_list: D018053:Arsenites; D004251:DNA Transposable Elements; C015001:arsenite; D001151:Arsenic