Scavenging of bacterial siderophores with engineered lipocalin proteins as an alternative antimicrobial strategy.

Scavenging of bacterial siderophores with engineered lipocalin proteins as an alternative antimicrobial strategy. Chembiochem. 2019 Oct 15;: Authors: Dauner M, Skerra A Abstract Iron acquisition mediated by siderophores, high-affinity chelators for which bacteria have evolved specific synthesis and uptake mechanisms, plays a crucial role in microbiology and in host-pathogen interactions. In the ongoing fight against bacterial infections this area has attracted biomedical interest. Beyond several approaches to interfere with the siderophore-mediated iron uptake from medicinal and immuno-chemistry, the development of high-affinity protein scavengers that tightly complex siderophores produced by pathogenic bacteria has appeared as a novel strategy. Such binding proteins were engineered based on siderocalin - also known as lipocalin 2 - an endogenous human scavenger of enterobactin and bacillibactin which controls the systemic spreading of commensal bacteria such as  Escherichia coli . Using combinatorial protein design, siderocalin was reshaped to bind several siderophores from  Pseudomonas aeruginosa and, in particular, petrobactin from  Bacillus anthracis , all of which are not recognized by the natural protein. Such engineered versions of siderocalin effectively suppress growth of corresponding pathogenic bacteria by deprivation from iron supply and bear potential to complement antibiotic therapy in situations of acute or persiste...
Source: Chembiochem - Category: Biochemistry Authors: Tags: Chembiochem Source Type: research