title: A Francisella tularensis pathogenicity island required for intramacrophage growth.
abstract: Francisella tularensis is a gram-negative, facultative intracellular pathogen that causes the highly infectious zoonotic disease tularemia. We have discovered a ca. 30-kb pathogenicity island of F. tularensis (FPI) that includes four large open reading frames (ORFs) of 2.5 to 3.9 kb and 13 ORFs of 1.5 kb or smaller. Previously, two small genes located near the center of the FPI were shown to be needed for intramacrophage growth. In this work we show that two of the large ORFs, located toward the ends of the FPI, are needed for virulence. Although most genes in the FPI encode proteins with amino acid sequences that are highly conserved between high- and low-virulence strains, one of the FPI genes is present in highly virulent type A F. tularensis, absent in moderately virulent type B F. tularensis, and altered in F. tularensis subsp. novicida, which is highly virulent for mice but avirulent for humans. The G+C content of a 17.7-kb stretch of the FPI is 26.6%, which is 6.6% below the average G+C content of the F. tularensis genome. This extremely low G+C content suggests that the DNA was imported from a microbe with a very low G+C-containing chromosome.
authors.affiliation: Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada. fnano@uvic.ca
authors.forename: Francis E
authors.initials: FE
authors.lastname: Nano
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.forename: Siobhán C
authors.initials: SC
authors.lastname: Cowley
authors.forename: Karl E
authors.initials: KE
authors.lastname: Klose
authors.forename: Karen K M
authors.initials: KK
authors.lastname: Cheung
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Roberts
authors.forename: Jagjit S
authors.initials: JS
authors.lastname: Ludu
authors.forename: Gregg W
authors.initials: GW
authors.lastname: Letendre
authors.forename: Anda I
authors.initials: AI
authors.lastname: Meierovics
authors.forename: Gwen
authors.initials: G
authors.lastname: Stephens
authors.forename: Karen L
authors.initials: KL
authors.lastname: Elkins
mesh_terms: D000818:Animals; D001482:Base Composition; D001483:Base Sequence; D005604:Francisella tularensis / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D044404:Genomic Islands / Q000502:physiology*; D008264:Macrophages / Q000382:microbiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D014774:Virulence