title: The complete genome sequence of Corynebacterium pseudotuberculosis FRC41 isolated from a 12-year-old girl with necrotizing lymphadenitis reveals insights into gene-regulatory networks contributing to virulence.
abstract: BACKGROUND
  Corynebacterium pseudotuberculosis is generally regarded as an important animal pathogen that rarely infects humans. Clinical strains are occasionally recovered from human cases of lymphadenitis, such as C. pseudotuberculosis FRC41 that was isolated from the inguinal lymph node of a 12-year-old girl with necrotizing lymphadenitis. To detect potential virulence factors and corresponding gene-regulatory networks in this human isolate, the genome sequence of C. pseudotuberculosis FCR41 was determined by pyrosequencing and functionally annotated.
  
  
  RESULTS
  Sequencing and assembly of the C. pseudotuberculosis FRC41 genome yielded a circular chromosome with a size of 2,337,913 bp and a mean G+C content of 52.2%. Specific gene sets associated with iron and zinc homeostasis were detected among the 2,110 predicted protein-coding regions and integrated into a gene-regulatory network that is linked with both the central metabolism and the oxidative stress response of FRC41. Two gene clusters encode proteins involved in the sortase-mediated polymerization of adhesive pili that can probably mediate the adherence to host tissue to facilitate additional ligand-receptor interactions and the delivery of virulence factors. The prominent virulence factors phospholipase D (Pld) and corynebacterial protease CP40 are encoded in the genome of this human isolate. The genome annotation revealed additional serine proteases, neuraminidase H, nitric oxide reductase, an invasion-associated protein, and acyl-CoA carboxylase subunits involved in mycolic acid biosynthesis as potential virulence factors. The cAMP-sensing transcription regulator GlxR plays a key role in controlling the expression of several genes contributing to virulence.
  
  
  CONCLUSIONS
  The functional data deduced from the genome sequencing and the extended knowledge of virulence factors indicate that the human isolate C. pseudotuberculosis FRC41 is equipped with a distinct gene set promoting its survival under unfavorable environmental conditions encountered in the mammalian host.
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: Lisa
authors.initials: L
authors.lastname: Ott
authors.forename: Jessica
authors.initials: J
authors.lastname: Schneider
authors.forename: Jasmin
authors.initials: J
authors.lastname: Schröder
authors.forename: Sebastian
authors.initials: S
authors.lastname: Jaenicke
authors.forename: Alexander
authors.initials: A
authors.lastname: Goesmann
authors.forename: Peter
authors.initials: P
authors.lastname: Husemann
authors.forename: Jens
authors.initials: J
authors.lastname: Stoye
authors.forename: Fernanda Alves
authors.initials: FA
authors.lastname: Dorella
authors.forename: Flavia Souza
authors.initials: FS
authors.lastname: Rocha
authors.forename: Siomar de Castro
authors.initials: Sde C
authors.lastname: Soares
authors.forename: Vívian
authors.initials: V
authors.lastname: D'Afonseca
authors.forename: Anderson
authors.initials: A
authors.lastname: Miyoshi
authors.forename: Jeronimo
authors.initials: J
authors.lastname: Ruiz
authors.forename: Artur
authors.initials: A
authors.lastname: Silva
authors.forename: Vasco
authors.initials: V
authors.lastname: Azevedo
authors.forename: Andreas
authors.initials: A
authors.lastname: Burkovski
authors.forename: Nicole
authors.initials: N
authors.lastname: Guiso
authors.forename: Olivier F
authors.initials: OF
authors.lastname: Join-Lambert
authors.forename: Samer
authors.initials: S
authors.lastname: Kayal
authors.forename: Andreas
authors.initials: A
authors.lastname: Tauch
mesh_terms: D001422:Bacterial Adhesion / Q000235:genetics; D001483:Base Sequence; D002648:Child; D016925:Corynebacterium pseudotuberculosis / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity* / Q000502:physiology; D005260:Female; D010861:Fimbriae, Bacterial / Q000235:genetics; D053263:Gene Regulatory Networks / Q000235:genetics*; D005798:Genes, Bacterial / Q000235:genetics; D016680:Genome, Bacterial / Q000235:genetics*; D020042:Histiocytic Necrotizing Lymphadenitis / Q000235:genetics* / Q000382:microbiology*; D006801:Humans; D007501:Iron / Q000378:metabolism; D008345:Manganese / Q000378:metabolism; D058977:Molecular Sequence Annotation; D018085:Regulon / Q000235:genetics; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism; D015032:Zinc / Q000378:metabolism
chemical_list: D037521:Virulence Factors; D008345:Manganese; D007501:Iron; D015032:Zinc