Capsular polysaccharides are key determinants of bacterial virulence, environmental persistence, and host immune evasion, yet their distribution across the bacterial tree remains incompletely characterised. This is largely due to the diversity of capsule biosynthesis systems and the limitations of existing annotation approaches when applied at scale. Here, we present a framework for identifying capsule-producing bacteria within large, uniformly assembled genome collections such as AllTheBacteria. We combine two complementary search strategies. First, we implement gene locus models based on sequence homology to known capsule biosynthesis clusters, extending concepts from tools like CapsuleFinder. Such models capsure conserved gene content and locus structure while remaining flexibile enough to account for much of the diversity within a capsule production system. Second, we incorporate structural homology searches for capsular proteins, enabling detection of functionally conserved components that may evade sequence-based methods due to high divergence. By integrating sequence- and structure-based evidence, we aim to improve sensitivity and robustness of capsule system detection across phylogenetically distant taxa. Projecting these results onto a marker-gene-based tree of all samples in AllTheBacteria, enables evolutionary analysis such as within-lineage capsule gain/loss and horizontal gene transfer. Our method enables consistent annotation of capsule biosynthesis production systems across millions of genomes. This provides a comprehensive view of capsule distribution, diversity, and evolutionary patterns. The framework is scalable, modular, and adaptable to expanding reference datasets, offering a deeper understanding of bacterial surface biology at ecosystem scale.

Co-authors: Teodora Mateeva, Samuel Horsfield, Stephanie Lo, Stephen Bentley, John Lees