2026/04/02 by Linlong Yu, Guanyue Xiong, Zhiyuan Li · 1 voice
Biochemistry, Genetics and Molecular Biology · Energy · #Bacterial Genetics and Biotechnology #Metalloenzymes and iron-sulfur proteins #Genomics and Phylogenetic Studies
paper · doi:10.1099/mgen.0.001671
openalex publication_date 2026/04/02 · openalex created_date 2026/04/03 · openalex updated_date 2026/07/27
Iron is a scarce yet essential nutrient for bacteria. Microbes often acquire iron by secreting siderophores, a diverse group of small molecules that form high-affinity complexes with iron for microbial uptake. Understanding microbial iron interaction networks requires detailed characterization of siderophore recognition specificity. In Gram-positive bacteria, substrate-binding proteins (SBPs) bind iron-siderophore complexes and deliver them to ABC transporters for import. However, the SBPs responsible for selective recognition remain poorly characterized, hindering large-scale data mining and network reconstruction. Here, we addressed this knowledge gap by systematically analysing siderophore uptake systems, first in five representative genera and then across a comprehensive dataset of 16,232 Gram-positive bacterial genomes. Through a pipeline integrating genome mining, coevolutionary analysis and structural modelling, we established PBP2 (PeriplaBP2) subtype SBPs as the primary siderophore recognizer family. We revealed that, unlike the physically clustered systems in Gram-negative bacteria, synthetase and recognizer genes in Gram-positive bacteria are sometimes genomically decoupled, yet display coordinated transcriptional regulation by iron-responsive transcription factors. Our findings underscore key differences between Gram-positive and Gram-negative iron acquisition systems, providing foundational knowledge for large-scale inference of siderophore-mediated microbial interactions.