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

ABSTRACT This study explored the microevolution of Shigella sonnei in China, focusing on 281 isolates exhibiting coresistance to ceftriaxone and azithromycin (cef R azi R ) and 99 ONPG‐negative isolates. Phylogenetic analysis revealed that waterborne outbreak strains, characterized by multidrug resistance (MDR) and cef R azi R , 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 cef R azi R 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 cef R azi R 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.