# Divergent Evolution and Local Establishment of Multidrug‐Resistant Shigella sonnei in China

**Authors:** Kangkang Liu, Jian Wang, Chaojie Yang, Yehong Yang, Xin Ge, Hongbo Liu, Xinying Du, Ying Xiang, Kaiyuan Min, Qi Wang, Hui Wang, Chao Wang, Huiqun Jia, Mingjuan Yang, Xiaoying Li, Ligui Wang, Yong Sun, Muti Mahe, Jiayong Zhao, Shijun Li, Deshan Yu, Stephen Baker, Jiangfeng Liu, Xuebin Xu, Hongbin Song, Shaofu Qiu, Juntao Yang

PMC · DOI: 10.1002/mco2.70569 · 2026-01-07

## TL;DR

The study traces the evolution of multidrug-resistant Shigella sonnei in China, revealing distinct genetic lineages and resistance mechanisms.

## Contribution

The paper identifies divergent evolutionary pathways and plasmid-mediated resistance mechanisms in Chinese Shigella sonnei strains.

## Key findings

- Shigella sonnei in China evolved into four clades, with distinct resistance mechanisms.
- CefRaziR in lineage I was mediated by an IncB/O/K/Z plasmid carrying multiple resistance genes.
- ONPG-negative variants resulted from a deletion spanning approximately 10 kbp.

## Abstract

This study explored the microevolution of Shigella sonnei in China, focusing on 281 isolates exhibiting coresistance to ceftriaxone and azithromycin (cefRaziR) and 99 ONPG‐negative isolates. Phylogenetic analysis revealed that waterborne outbreak strains, characterized by multidrug resistance (MDR) and cefRaziR, clustered within the predominant domestic lineage I. In contrast, sporadic MDR strains harboring a wider array of antimicrobial resistance (AMR) genes were primarily associated with lineage II. The cefRaziR phenotype in lineage I was mediated by an IncB/O/K/Z plasmid carrying bla
CTX‐M‐14, mphA, aac(3)‐IId, dfrA17, aadA5, and sul1 genes. Lineage II strains acquired cefRaziR through a distinct IncFII plasmid possessing bla
CTX‐M‐15, ermB, and mphA genes, and additionally carried a separate IncB/O/K/Z plasmid backbone with bla
TEM‐1, dfrA12, sul2, strA, strB, tet(A), and aac(3)‐IId genes. Conversion to the ONPG‐negative phenotype was linked to a deletion spanning approximately 10 kbp, which included two insertion sequences (IS1 and IS600), the mhpBAR operon, and the lacIZY operon. Genomic comparisons identified 66 SNPs and 9 accessory genes correlated with lineage II, and 23 SNPs with 9 accessory genes associated with ONPG‐negative variants. Ongoing surveillance of S. sonnei epidemic clones is essential to elucidate their microevolution, track transmission, and assess public health implications.

• Evolutionary history and local establishment of Chinese Shigella sonnei are unclear.

• Chinese S. sonnei developed into four clades and ONPG‐negative variants.

• The antimicrobial resistance phenotype of Clade I was due to an IncB/O/K/Z plasmid.

• Antimicrobial resistance of Clade II was due to IncFII and IncB/O/K/Z plasmids.

• The ONPG‐negative phenotype was attributed to the deletion of a nucleotide region.

## Linked entities

- **Genes:** aac(3)-IId (aminoglycoside N-acetyltransferase AAC(3)-IId) [NCBI Gene 50216977], dfrA17 (trimethoprim-resistant dihydrofolate reductase DfrA17) [NCBI Gene 83039323], sul-1 (Putative extracellular sulfatase Sulf-1 homolog) [NCBI Gene 180619], erm(B) (23S rRNA (adenine(2058)-N(6))-methyltransferase Erm(B)) [NCBI Gene 8154416], dfrA12 (trimethoprim-resistant dihydrofolate reductase DfrA12) [NCBI Gene 75204014], sul-2 (Sulfatase N-terminal domain-containing protein) [NCBI Gene 179194], STRA (serine/threonine kinase receptor associated protein) [NCBI Gene 105481604], STRB (spermatid perinuclear RNA binding protein) [NCBI Gene 105463893], tet(A) (tetracycline efflux MFS transporter Tet(A)) [NCBI Gene 33941499], IS1 (Adolescent idiopathic scoliosis) [NCBI Gene 260402]
- **Species:** Shigella sonnei (taxon 624), Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** strA [NCBI Gene 4362687], strB [NCBI Gene 4362688], tet(A) [NCBI Gene 4362685]
- **Chemicals:** ONPG (MESH:C055012), ceftriaxone (MESH:D002443), azithromycin (MESH:D017963), cefRaziR (-)
- **Species:** Shigella sonnei (species) [taxon 624]

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12778403/full.md

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Source: https://tomesphere.com/paper/PMC12778403