Flying under the radar: The non‐canonical biochemistry and molecular biology of petrobactin from Bacillus anthracis

Summary The dramatic, rapid growth of Bacillus anthracis that occurs during systemic anthrax implies a crucial requirement for the efficient acquisition of iron. While recent advances in our understanding of B. anthracis iron acquisition systems indicate the use of strategies similar to other pathogens, this review focuses on unique features of the major siderophore system, petrobactin. Ways that petrobactin differs from other siderophores include: A. unique ferric iron binding moieties that allow petrobactin to evade host immune proteins; B. a biosynthetic operon that encodes enzymes from both major siderophore biosynthesis classes; C. redundancy in membrane transport systems for acquisition of Fe‐petrobactin holo‐complexes; and, D. regulation that appears to be controlled predominately by sensing the host‐like environmental signals of temperature, CO2 levels and oxidative stress, as opposed to canonical sensing of intracellular iron levels. We argue that these differences contribute in meaningful ways to B. anthracis pathogenesis. This review will also outline current major gaps in our understanding of the petrobactin iron acquisition system, some projected means for exploiting current knowledge, and potential future research directions. This review aims to discuss the current state of knowledge regarding petrobactin use by the pathogen Bacillus anthracis. Used to gather iron during infections, petrobactin differs from other siderophores in a number of ways including: regulation, biosynthesis, structure, and transport. We argue that these differences enhance the pathogenic ability of B. anthracis through increased iron acquisition, and identify areas needing further research.