title: Comparative analysis of Klebsiella pneumoniae genomes identifies a phospholipase D family protein as a novel virulence factor.
abstract: BACKGROUND
  Klebsiella pneumoniae strains are pathogenic to animals and humans, in which they are both a frequent cause of nosocomial infections and a re-emerging cause of severe community-acquired infections. K. pneumoniae isolates of the capsular serotype K2 are among the most virulent. In order to identify novel putative virulence factors that may account for the severity of K2 infections, the genome sequence of the K2 reference strain Kp52.145 was determined and compared to two K1 and K2 strains of low virulence and to the reference strains MGH 78578 and NTUH-K2044.
  
  
  RESULTS
  In addition to diverse functions related to host colonization and virulence encoded in genomic regions common to the four strains, four genomic islands specific for Kp52.145 were identified. These regions encoded genes for the synthesis of colibactin toxin, a putative cytotoxin outer membrane protein, secretion systems, nucleases and eukaryotic-like proteins. In addition, an insertion within a type VI secretion system locus included sel1 domain containing proteins and a phospholipase D family protein (PLD1). The pld1 mutant was avirulent in a pneumonia model in mouse. The pld1 mRNA was expressed in vivo and the pld1 gene was associated with K. pneumoniae isolates from severe infections. Analysis of lipid composition of a defective E. coli strain complemented with pld1 suggests an involvement of PLD1 in cardiolipin metabolism.
  
  
  CONCLUSIONS
  Determination of the complete genome of the K2 reference strain identified several genomic islands comprising putative elements of pathogenicity. The role of PLD1 in pathogenesis was demonstrated for the first time and suggests that lipid metabolism is a novel virulence mechanism of K. pneumoniae.
authors.affiliation: Institut Pasteur - Pathogénie Microbienne Moléculaire, Paris, France. llery@biof.ufrj.br.
authors.forename: Letícia M S
authors.initials: LM
authors.lastname: Lery
authors.forename: Lionel
authors.initials: L
authors.lastname: Frangeul
authors.forename: Anna
authors.initials: A
authors.lastname: Tomas
authors.forename: Virginie
authors.initials: V
authors.lastname: Passet
authors.forename: Ana S
authors.initials: AS
authors.lastname: Almeida
authors.forename: Suzanne
authors.initials: S
authors.lastname: Bialek-Davenet
authors.forename: Valérie
authors.initials: V
authors.lastname: Barbe
authors.forename: José A
authors.initials: JA
authors.lastname: Bengoechea
authors.forename: Philippe
authors.initials: P
authors.lastname: Sansonetti
authors.forename: Sylvain
authors.initials: S
authors.lastname: Brisse
authors.forename: Régis
authors.initials: R
authors.lastname: Tournebize
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D058947:Bacterial Secretion Systems / Q000235:genetics; D005798:Genes, Bacterial / Q000235:genetics; D016680:Genome, Bacterial / Q000235:genetics*; D044404:Genomic Islands / Q000235:genetics; D007711:Klebsiella pneumoniae / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity*; D050356:Lipid Metabolism / Q000235:genetics; D051379:Mice; D058977:Molecular Sequence Annotation; D008969:Molecular Sequence Data; D005810:Multigene Family; D016254:Mutagenesis, Insertional / Q000235:genetics; D010739:Phospholipase D / Q000737:chemistry / Q000235:genetics*; D010957:Plasmids / Q000235:genetics; D016415:Sequence Alignment; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D037521:Virulence Factors; D010739:Phospholipase D