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.

Keywords

microevolution / multidrug resistance / ONPG-negative variants / Shigella sonnei / whole-genome sequencing

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