title: Pangenomic study of Corynebacterium diphtheriae that provides insights into the genomic diversity of pathogenic isolates from cases of classical diphtheria, endocarditis, and pneumonia.
abstract: Corynebacterium diphtheriae is one of the most prominent human pathogens and the causative agent of the communicable disease diphtheria. The genomes of 12 strains isolated from patients with classical diphtheria, endocarditis, and pneumonia were completely sequenced and annotated. Including the genome of C. diphtheriae NCTC 13129, we herewith present a comprehensive comparative analysis of 13 strains and the first characterization of the pangenome of the species C. diphtheriae. Comparative genomics showed extensive synteny and revealed a core genome consisting of 1,632 conserved genes. The pangenome currently comprises 4,786 protein-coding regions and increases at an average of 65 unique genes per newly sequenced strain. Analysis of prophages carrying the diphtheria toxin gene tox revealed that the toxoid vaccine producer C. diphtheriae Park-Williams no. 8 has been lysogenized by two copies of the ω(tox)(+) phage, whereas C. diphtheriae 31A harbors a hitherto-unknown tox(+) corynephage. DNA binding sites of the tox-controlling regulator DtxR were detected by genome-wide motif searches. Comparative content analysis showed that the DtxR regulons exhibit marked differences due to gene gain, gene loss, partial gene deletion, and DtxR binding site depletion. Most predicted pathogenicity islands of C. diphtheriae revealed characteristics of horizontal gene transfer. The majority of these islands encode subunits of adhesive pili, which can play important roles in adhesion of C. diphtheriae to different host tissues. All sequenced isolates contain at least two pilus gene clusters. It appears that variation in the distributed genome is a common strategy of C. diphtheriae to establish differences in host-pathogen interactions.
authors.affiliation: Institut für Genomforschung und Systembiologie, Centrum für Biotechnologie, Universität Bielefeld, Bielefeld, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Trost
authors.forename: Jochen
authors.initials: J
authors.lastname: Blom
authors.forename: Siomar de Castro
authors.initials: Sde C
authors.lastname: Soares
authors.forename: I-Hsiu
authors.initials: IH
authors.lastname: Huang
authors.forename: Arwa
authors.initials: A
authors.lastname: Al-Dilaimi
authors.forename: Jasmin
authors.initials: J
authors.lastname: Schröder
authors.forename: Sebastian
authors.initials: S
authors.lastname: Jaenicke
authors.forename: Fernanda A
authors.initials: FA
authors.lastname: Dorella
authors.forename: Flavia S
authors.initials: FS
authors.lastname: Rocha
authors.forename: Anderson
authors.initials: A
authors.lastname: Miyoshi
authors.forename: Vasco
authors.initials: V
authors.lastname: Azevedo
authors.forename: Maria P
authors.initials: MP
authors.lastname: Schneider
authors.forename: Artur
authors.initials: A
authors.lastname: Silva
authors.forename: Thereza C
authors.initials: TC
authors.lastname: Camello
authors.forename: Priscila S
authors.initials: PS
authors.lastname: Sabbadini
authors.forename: Cíntia S
authors.initials: CS
authors.lastname: Santos
authors.forename: Louisy S
authors.initials: LS
authors.lastname: Santos
authors.forename: Raphael
authors.initials: R
authors.lastname: Hirata
authors.forename: Ana L
authors.initials: AL
authors.lastname: Mattos-Guaraldi
authors.forename: Androulla
authors.initials: A
authors.lastname: Efstratiou
authors.forename: Michael P
authors.initials: MP
authors.lastname: Schmitt
authors.forename: Hung
authors.initials: H
authors.lastname: Ton-That
authors.forename: Andreas
authors.initials: A
authors.lastname: Tauch
mesh_terms: D003353:Corynebacterium diphtheriae / Q000235:genetics* / Q000302:isolation & purification*; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004165:Diphtheria / Q000382:microbiology*; D004697:Endocarditis, Bacterial / Q000382:microbiology*; D017353:Gene Deletion; D022761:Gene Transfer, Horizontal; D005798:Genes, Bacterial; D014644:Genetic Variation; D016680:Genome, Bacterial; D044404:Genomic Islands; D006017:Glycolipids / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D018410:Pneumonia, Bacterial / Q000382:microbiology*; D039002:Prophages / Q000235:genetics; D018085:Regulon; D017422:Sequence Analysis, DNA
chemical_list: D004269:DNA, Bacterial; D006017:Glycolipids; C034696:corynetoxins