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.

Patients with tuberculosis resistant to isoniazid but susceptible to rifampicin (H^r-R^s TB) remain a neglected demographic, despite a high disease burden and poor outcomes of these patients. The aim of this study was to investigate the characteristics of isoniazid-resistance-related mutations in Mycobacterium tuberculosis and resistance rates to drugs included in WHO-recommended regimens for H^r-R^s patients.

Mycobacterium tuberculosis isolates (n = 4922) obtained from national tuberculosis drug-resistance surveillance were subjected to whole-genome sequencing to identify H^r-R^s strains. The minimal inhibitory concentrations (MICs) were established for the H^r-R^s strains to determine the isoniazid resistance levels. We also identified drug-resistance-associated mutations for five drugs (fluoroquinolones, ethambutol, pyrazinamide, streptomycin, and amikacin) in the H^r-R^s strains.

Of the 4922 strains, 384 (7.8 %) were H^r-R^s. The subculture of seven strains failed, so 377 (98.2 %) strains underwent phenotypic MIC testing. Among the 384 genotypic H^r-R^s strains, 242 (63.0 %) contained thekatG Ser315Thr substitution; 115 (29.9 %) contained the -15C>T in the promoter region of the fabG1 gene; and 16 (4.2 %) contained Ser315Asn in the katG gene. Of the 239 strains with the Ser315Thr substitution, 229 (95.8 %) had MIC ≥ 2 μg/mL, and of the 114 strains with the -15C>T mutation, 103 (90.4 %) had 0.25 μg/mL ≤ MIC ≤ 1 μg/mL. The genotypic resistance rates were 0.8 % (3/384) for pyrazinamide, 2.3 % (9/384) for ethambutol and fluoroquinolones; 39.6 % (152/384) of the strains were resistant to streptomycin, but only 0.5 % (2/384) of the strains were resistant to amikacin.

Ser315Thr in katG was the predominant mutation conferring the H^r-R^s phenotype, followed by thefabG1 -15C>T mutation. The combination of rifampicin, pyrazinamide, ethambutol, and levofloxacin should be effective in the treatment of patients with H^r-R^s tuberculosis because the resistance rates for these drugs in China are low.