Premium
Reprogramming Human Siderocalin To Neutralize Petrobactin, the Essential Iron Scavenger of Anthrax Bacillus
Author(s) -
Dauner Martin,
Eichinger Andreas,
Lücking Genia,
Scherer Siegfried,
Skerra Arne
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201807442
Subject(s) - bacillus anthracis , bacillus cereus , siderophore , microbiology and biotechnology , chemistry , ligand (biochemistry) , lipocalin , virulence , bacteria , cereus , biology , biochemistry , gene , receptor , genetics
Bacillus anthracis owes its pronounced virulence—apart from specific toxins—to a twofold import mechanism for Fe III ions. This pathogenic bacterium secretes the siderophores bacillibactin (BB) and petrobactin (PB), of which only BB is neutralized by human siderocalin, an abundant lipocalin in plasma. We describe its reshaping via combinatorial protein design to bind PB⋅Fe III instead of BB⋅Fe III , and with even higher affinity ( K D ≈20 p m ). X‐ray crystallographic analysis of the resulting “petrocalin” in complex with PB⋅Ga III reveals a positively charged ligand pocket while the extended butterfly‐like conformation of the bound PB provides a rationale for the missing recognition by the natural siderocalin. In microbiological studies, a combination of petrocalin and siderocalin effectively suppressed the growth of a BB + /PB + strain of Bacillus cereus under iron‐limiting culture conditions. Thus, our reprogrammed lipocalin may offer novel treatment options for devastating infections caused by B. anthracis .