Shigella spp. remains a major cause of diarrheal disease globally, with escalating antimicrobial resistance and high transmissibility posing persistent public health threats. However, large-scale spatiotemporal genomic analyses are scarce, particularly for the neglected species S. boydii and S. dysenteriae, limiting global surveillance and vaccine development.

We curated 42,189 Shigella genomes from worldwide sources (1914−2024) and performed systematic genomic characterization on 17,360 high-quality genomes using in silico serotyping, core-genome multilocus sequence typing (cgMLST), and antimicrobial resistance gene (ARG) analysis.

This largest dataset to date encompasses 68 countries across six continents, yet sampling is heavily skewed toward high-income regions. We identified 50 serotypes and 166 sequence types (STs), uncovering strong serotype−ST associations and pronounced geographical predilections. Critically, the distribution of predominant serotypes reveals gaps in coverage by current vaccine candidates in some high-burden settings. cgMLST provided molecular evidence for extensive cross-border transmission, particularly among S. flexneri and S. sonnei. ARGs were detected in 99.74% of genomes, with carriage rates displaying distinct continental patterns and significant temporal increases for quinolone, macrolide, and extended-spectrum β-lactamase genes; the colistin resistance gene mcr-1.1 was identified in S. sonnei. Notably, the under-characterized species S. boydii and S. dysenteriae exhibited considerable serotype diversity and international dissemination.

This study delivers the most comprehensive spatiotemporal and species-inclusive genomic resource for Shigella to date, unveiling serotype gaps in vaccine strategies, cross-border transmission dynamics, and spatiotemporal variations in resistance gene distribution.