title: Bacillus anthracis phospholipases C facilitate macrophage-associated growth and contribute to virulence in a murine model of inhalation anthrax.
abstract: Several models of anthrax pathogenesis suggest that early in the infectious process Bacillus anthracis endospores germinate and outgrow into vegetative bacilli within phagocytes before being released into the blood. Here, we define the respective contributions of three phospholipases C (PLCs) to the pathogenesis of B. anthracis. Genetic deletions of the PLCs were made in the Sterne 7702 background, resulting in the respective loss of their activities. The PLCs were redundant both in tissue culture and in murine models of anthrax. Deletion of all three PLC genes was required for attenuation of virulence in mice after intratracheal inoculation. This attenuation may be attributed to the inability of the PLC-null strain to grow in association with the macrophage. Complementation of these defects in both models of anthrax was achieved by expression of the PLC genes in trans. The functional redundancy between PLCs in the virulence of B. anthracis implies that their activities are important for anthrax pathogenesis.
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109-0620, USA. pchanna@umich.edu
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Heffernan
authors.forename: Brendan
authors.initials: B
authors.lastname: Thomason
authors.forename: Amy
authors.initials: A
authors.lastname: Herring-Palmer
authors.forename: Lee
authors.initials: L
authors.lastname: Shaughnessy
authors.forename: Rod
authors.initials: R
authors.lastname: McDonald
authors.forename: Nathan
authors.initials: N
authors.lastname: Fisher
authors.forename: Gary B
authors.initials: GB
authors.lastname: Huffnagle
authors.forename: Philip
authors.initials: P
authors.lastname: Hanna
mesh_terms: D000818:Animals; D000881:Anthrax / Q000201:enzymology* / Q000382:microbiology*; D001408:Bacillus anthracis / Q000201:enzymology* / Q000254:growth & development* / Q000472:pathogenicity; D001854:Bone Marrow Cells / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D007442:Intubation, Intratracheal; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D010738:Type C Phospholipases / Q000235:genetics / Q000502:physiology*; D014774:Virulence
chemical_list: D010738:Type C Phospholipases