title: Iron acquisition in Bacillus cereus: the roles of IlsA and bacillibactin in exogenous ferritin iron mobilization.
abstract: In host-pathogen interactions, the struggle for iron may have major consequences on the outcome of the disease. To overcome the low solubility and bio-availability of iron, bacteria have evolved multiple systems to acquire iron from various sources such as heme, hemoglobin and ferritin. The molecular basis of iron acquisition from heme and hemoglobin have been extensively studied; however, very little is known about iron acquisition from host ferritin, a 24-mer nanocage protein able to store thousands of iron atoms within its cavity. In the human opportunistic pathogen Bacillus cereus, a surface protein named IlsA (Iron-regulated leucine rich surface protein type A) binds heme, hemoglobin and ferritin in vitro and is involved in virulence. Here, we demonstrate that IlsA acts as a ferritin receptor causing ferritin aggregation on the bacterial surface. Isothermal titration calorimetry data indicate that IlsA binds several types of ferritins through direct interaction with the shell subunits. UV-vis kinetic data show a significant enhancement of iron release from ferritin in the presence of IlsA indicating for the first time that a bacterial protein might alter the stability of the ferritin iron core. Disruption of the siderophore bacillibactin production drastically reduces the ability of B. cereus to utilize ferritin for growth and results in attenuated bacterial virulence in insects. We propose a new model of iron acquisition in B. cereus that involves the binding of IlsA to host ferritin followed by siderophore assisted iron uptake. Our results highlight a possible interplay between a surface protein and a siderophore and provide new insights into host adaptation of B. cereus and general bacterial pathogenesis.
authors.affiliation: INRA, UMR 1319 Micalis, La Minière, Guyancourt, France ; AgroParisTech, UMR Micalis, Jouy en Josas, France.
authors.forename: Diego
authors.initials: D
authors.lastname: Segond
authors.affiliation: INRA, UMR 1319 Micalis, La Minière, Guyancourt, France ; AgroParisTech, UMR Micalis, Jouy en Josas, France ; Laboratory of Biotechnology, Saint-Joseph University, Beyrouth, Lebanon.
authors.forename: Elise
authors.initials: E
authors.lastname: Abi Khalil
authors.affiliation: INRA, UMR 1319 Micalis, La Minière, Guyancourt, France ; AgroParisTech, UMR Micalis, Jouy en Josas, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Buisson
authors.affiliation: INRA, UMR 1319 Micalis, La Minière, Guyancourt, France ; AgroParisTech, UMR Micalis, Jouy en Josas, France ; Department of Medicine, Section of Infectious Diseases, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Nadine
authors.initials: N
authors.lastname: Daou
authors.affiliation: Laboratory of Biotechnology, Saint-Joseph University, Beyrouth, Lebanon.
authors.forename: Mireille
authors.initials: M
authors.lastname: Kallassy
authors.affiliation: INRA, UMR 1319 Micalis, La Minière, Guyancourt, France ; AgroParisTech, UMR Micalis, Jouy en Josas, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Lereclus
authors.affiliation: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Arosio
authors.affiliation: Department of Chemistry, State University of New York at Potsdam, Potsdam, New York, United States of America.
authors.forename: Fadi
authors.initials: F
authors.lastname: Bou-Abdallah
authors.affiliation: INRA, UMR 1319 Micalis, La Minière, Guyancourt, France ; AgroParisTech, UMR Micalis, Jouy en Josas, France.
authors.forename: Christina
authors.initials: C
authors.lastname: Nielsen Le Roux
mesh_terms: D000818:Animals; D001409:Bacillus cereus / Q000378:metabolism / Q000472:pathogenicity*; D001426:Bacterial Proteins / Q000378:metabolism; D005293:Ferritins / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D054884:Host-Pathogen Interactions / Q000502:physiology*; D007501:Iron / Q000378:metabolism*; D009036:Moths / Q000378:metabolism / Q000382:microbiology; D009842:Oligopeptides / Q000378:metabolism*; D014774:Virulence / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D009842:Oligopeptides; C430721:bacillibactin; D005293:Ferritins; D007501:Iron