title: Bacillus anthracis interacts with plasmin(ogen) to evade C3b-dependent innate immunity.
abstract: The causative agent of anthrax, Bacillus anthracis, is capable of circumventing the humoral and innate immune defense of the host and modulating the blood chemistry in circulation to initiate a productive infection. It has been shown that the pathogen employs a number of strategies against immune cells using secreted pathogenic factors such as toxins. However, interference of B. anthracis with the innate immune system through specific interaction of the spore surface with host proteins such as the complement system has heretofore attracted little attention. In order to assess the mechanisms by which B. anthracis evades the defense system, we employed a proteomic analysis to identify human serum proteins interacting with B. anthracis spores, and found that plasminogen (PLG) is a major surface-bound protein. PLG efficiently bound to spores in a lysine- and exosporium-dependent manner. We identified α-enolase and elongation factor tu as PLG receptors. PLG-bound spores were capable of exhibiting anti-opsonic properties by cleaving C3b molecules in vitro and in rabbit bronchoalveolar lavage fluid, resulting in a decrease in macrophage phagocytosis. Our findings represent a step forward in understanding the mechanisms involved in the evasion of innate immunity by B. anthracis through recruitment of PLG resulting in the enhancement of anti-complement and anti-opsonization properties of the pathogen.
authors.affiliation: National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, Virginia, United States of America. mchung3@gmu.edu
authors.forename: Myung-Chul
authors.initials: MC
authors.lastname: Chung
authors.forename: Jessica H
authors.initials: JH
authors.lastname: Tonry
authors.forename: Aarthi
authors.initials: A
authors.lastname: Narayanan
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Manes
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Mackie
authors.forename: Bradford
authors.initials: B
authors.lastname: Gutting
authors.forename: Dhritiman V
authors.initials: DV
authors.lastname: Mukherjee
authors.forename: Taissia G
authors.initials: TG
authors.lastname: Popova
authors.forename: Fatah
authors.initials: F
authors.lastname: Kashanchi
authors.forename: Charles L
authors.initials: CL
authors.lastname: Bailey
authors.forename: Serguei G
authors.initials: SG
authors.lastname: Popov
mesh_terms: D000818:Animals; D001408:Bacillus anthracis / Q000187:drug effects / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003179:Complement C3b / Q000276:immunology*; D015180:Electrophoresis, Gel, Two-Dimensional; D005341:Fibrinolysin / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D051379:Mice; D009895:Opsonin Proteins / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011817:Rabbits; D011994:Recombinant Proteins / Q000378:metabolism; D013171:Spores, Bacterial / Q000187:drug effects / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology
chemical_list: D009895:Opsonin Proteins; D011994:Recombinant Proteins; D003179:Complement C3b; D010958:Plasminogen; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator