Divergent Evolution and Local Establishment of Multidrug‐Resistant <i>Shigella sonnei</i> in China

This study explored the microevolution of <i>Shigella sonnei</i> in China, focusing on 281 isolates exhibiting coresistance to ceftriaxone and azithromycin (cef^Razi^R) and 99 ONPG-negative isolates. Phylogenetic analysis revealed that waterborne outbreak strains, characterized by multidrug resistance (MDR) and cef^Razi^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^Razi^R phenotype in lineage I was mediated by an IncB/O/K/Z plasmid carrying <i>bla</i> _CTX-M-14, <i>mphA</i>, <i>aac(3)-IId</i>, <i>dfrA17, aadA5</i>, and <i>sul1</i> genes. Lineage II strains acquired cef^Razi^R through a distinct IncFII plasmid possessing <i>bla</i> _CTX-M-15, <i>ermB</i>, and <i>mphA</i> genes, and additionally carried a separate IncB/O/K/Z plasmid backbone with <i>bla</i> _TEM-1, <i>dfrA12</i>, <i>sul2</i>, <i>strA</i>, <i>strB</i>, <i>tet(A)</i>, and <i>aac(3)-IId</i> 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 <i>mhpBAR</i> operon, and the <i>lacIZY</i> 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 <i>S. sonnei</i> epidemic clones is essential to elucidate their microevolution, track transmission, and assess public health implications.