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<p>Ceftiofur resistance in canine clinical <i>Escherichia coli</i> is usually associated with extended-spectrum β-lactamases (ESBLs) or AmpC β-lactamases. However, some isolates display elevated ceftiofur minimum inhibitory concentrations (MICs) without carrying these known resistance genes. In this study, we identified a phenotype-genotype discordant canine clinical <i>E. coli</i> isolate named 231255, with a ceftiofur MIC of 8&#xa0;μg/mL. Routine resistance gene screening detected only <i>bla</i><sub>TEM-1</sub> and a chromosomal <i>bla</i><sub>EC</sub> variant, <i>bla</i><sub>EC-1149</sub>, which could not adequately explain the elevated ceftiofur MIC. To investigate the underlying mechanism, a genomic library was constructed from genomic DNA of isolate 231255 and screened on ceftiofur-containing plates. Positive clones revealed one candidate determinant: an altered <i>ftsI</i> fragment encoding&#xa0;penicillin-binding protein 3&#xa0;(PBP3) with a four-amino-acid YRIN insertion downstream of residue P333, previously identified in human <i>E. coli</i>. Previous studies have shown that this type of YRIN/YRIK insertion alone can reduce susceptibility to PBP3-targeting β-lactams, particularly aztreonam and ceftazidime. Functional validation showed that recombinant plasmids carrying the altered <i>ftsI</i> consistently increased the ceftiofur MIC to 4&#xa0;μg/mL in different recipient backgrounds. These findings provide experimental evidence that <i>ftsI</i>/PBP3 alteration can elevate ceftiofur MIC in canine <i>E. coli</i>. Notably, the isolate belonged to ST410, and phylogenetic analysis indicated that it was not confined to a dog-associated background but instead clustered within a broader lineage shared across multiple sources, highlighting the need for potential dissemination of this mechanism and its associated resistant lineages at the human-companion animal interface.</p>

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A four-amino-acid YRIN insertion in ftsI reduced ceftiofur susceptibility in a canine Escherichia coli isolate

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月23日

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  • Xukun Dang,
  • Zeshi Chen,
  • Rina Bai,
  • Junyao Jiang,
  • Weishuai Zhai,
  • Shizhen Ma,
  • Lu Liu,
  • Dejun Liu,
  • Zhaofei Xia,
  • Zhangqi Shen,
  • Yang Wang,
  • Siyu Chen

摘要

Ceftiofur resistance in canine clinical Escherichia coli is usually associated with extended-spectrum β-lactamases (ESBLs) or AmpC β-lactamases. However, some isolates display elevated ceftiofur minimum inhibitory concentrations (MICs) without carrying these known resistance genes. In this study, we identified a phenotype-genotype discordant canine clinical E. coli isolate named 231255, with a ceftiofur MIC of 8 μg/mL. Routine resistance gene screening detected only blaTEM-1 and a chromosomal blaEC variant, blaEC-1149, which could not adequately explain the elevated ceftiofur MIC. To investigate the underlying mechanism, a genomic library was constructed from genomic DNA of isolate 231255 and screened on ceftiofur-containing plates. Positive clones revealed one candidate determinant: an altered ftsI fragment encoding penicillin-binding protein 3 (PBP3) with a four-amino-acid YRIN insertion downstream of residue P333, previously identified in human E. coli. Previous studies have shown that this type of YRIN/YRIK insertion alone can reduce susceptibility to PBP3-targeting β-lactams, particularly aztreonam and ceftazidime. Functional validation showed that recombinant plasmids carrying the altered ftsI consistently increased the ceftiofur MIC to 4 μg/mL in different recipient backgrounds. These findings provide experimental evidence that ftsI/PBP3 alteration can elevate ceftiofur MIC in canine E. coli. Notably, the isolate belonged to ST410, and phylogenetic analysis indicated that it was not confined to a dog-associated background but instead clustered within a broader lineage shared across multiple sources, highlighting the need for potential dissemination of this mechanism and its associated resistant lineages at the human-companion animal interface.