Pangenome analysis of human and aquaculture Streptococcus agalactiae identifies integrative conjugative elements as major carriers of antimicrobial resistance asymmetry

Abstract Streptococcus agalactiae (Group B Streptococcus ) causes neonatal sepsis in humans and is an emerging pathogen of farmed tilapia, yet how mobile genetic elements differ between these hosts is uncharacterized. We analyzed 259 genomes (159 human, 100 fish) from 25 countries, integrating pangenome-wide association, resistance gene profiling and coordinate-level mobile element analysis. Integrative conjugative elements (ICEs) were far more prevalent in human than fish genomes (73.6% versus 12.0%; odds ratio 20.43, P = 1.72×10⁻²³), and human genomes carried more acquired resistance genes (median 1 versus 0; P = 7.3×10⁻²⁶). Resistance genes lay inside ICE regions in 57.9% of human but 4.0% of fish genomes (P = 4.4×10⁻²¹); 55% of all resistance gene copies, and 81% of tet (M) copies, were ICE-located, versus 5% of random positions, although erm (A), spw , lsa (E) and lnu (B) never were. In fish, ICE-located resistance occurred in four genomes, three carrying tet (M) on Tn916-like elements. No β-lactam resistance gene was detected. Pangenome-wide association identified 27 host-associated gene families, with the adhesin lmb and four mobile-element genes the most robust. The zoonotic lineage ST283 occurred in both hosts. ICEs are the major identified carriers of acquired resistance in S. agalactiae and are sharply asymmetric across hosts, highlighting lineages for One Health surveillance.