Introduction to the 4th Biometals webinars, Significance of chirality in siderophores: From marine microbes to pathogens, Perspectives on copper import in Streptococcus pneumoniae

Abstract

Introduction to the 4th Biometals webinarsWelcome to the 4th international webinars series For those who don't already know, these webinars have been set up by the international Biometals society and the journal Biometals with the help of Cassyni platform. • The aim is to promote research in the field of metal interactions in biology and to encourage the interdisciplinary exchange of information at international level. Today we welcome two speakers: Alison Butler will be talking about Significance of chirality in siderophores: From marine microbes to pathogens. Fe is essential but may be scarce in some environment and its complexation and uptake require strong ferric iron chelators, siderophores that solubilize this “easily rusty ions”. Several hundreds of structures of siderophores have been described. I am sure Alison knows almost all of them! More than 99% of the dissolved iron in the ocean is bound to organic ligands, as complexation of iron to organic ligands can increase the solubility of iron by orders of magnitude and prevent precipitation and scavenging. Interestingly, marine microorganisms and pathogens develop some tricks for marine siderophores optimization and uptake and Alison will talk about that. The 2nd speaker, Michael Johnson will be talking about copper import in Streptococcus pneumoniae. Copper is also an essential element for biological life but as other it can be toxic when its homeostasis is uncontrolled. Starting from antiquity, copper has been used as a bactericidal agent. The demonstration of its efficiency as Cu metal to inhibit bacterial growth make it still useful in medical environment. In cellulo, copper ions are supposed to go from one protein partner to another to avoid its redox reactivity (as Fe) that can produce reactive oxygen species. Its uptake in all cells, prokaryotes as eukaryotes is under tight control but only few Cuprophores have been described. Today Michael will discuss copper homeostasis in the pathogen Streptococcus pneumonia. Significance of chirality in siderophores: From marine microbes to pathogensSpecific types of microbial siderophores can be identified in microbial genomes based on characteristics of the Fe(III)-binding groups. We are particularly interested in chirality in siderophores, both within the siderophore ligand, as well as at the Fe(III) site. In the large class of peptidic siderophores, beta-hydroxyaspartate is often present as an Fe(III)-binding ligand. Biosynthesis of beta-hydroxyaspartate is intriguing in regards to the stereoselective control of hydroxylation catalyzed by non heme iron enzymes. The origin of the beta-hydroxyaspartate diastereomers in these siderophores is revealed in the microbial genomes. A new class of tris catechol siderophores in marine and pathogenic microbes is based on a variation of enterobactin, adding a combinatoric suite of D- and L- cationic amino acids. Variation in amino acid chirality directs stereochemistry at the Fe(III) site, which in turn profoundly affects microbial growth. While microbial genome mining encompasses microbes from all environments, marine microbes are found to be prominent in our investigations into the discovery, biosynthesis and reactivity of beta-hydroxyaspartate, and triscatecholate siderophores. These and further developments on the bioinorganic chemistry of siderophores containing beta-hydroxyaspartate, and catechol will be presented.Perspectives on copper import in Streptococcus pneumoniaeCopper is broadly toxic to microbes at the host-pathogen interface. However, how copper gets into many bacteria has been a difficult question, considering they do not have dedicated copper importers. Somewhat complicating this analysis is that many of these organisms are studied in complex media containing an abundance of resources they would not normally encounter in the host or environment. In this talk, I will describe steps we have taken to use a minimal media for growing Streptococcus pneumoniae, a causative agent of multiple diseases including pneumonia, middle ear infections, and sepsis in the defined, minimal, and host-adjacent RPMI media, and how it led us to find that there was an iron-dependent increase in intrabacterial copper.