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Background <p>The combination of monoclonal antibodies with aminoglycosides represents a promising strategy to counter the increasing prevalence of aminoglycoside resistance in avian pathogenic <i>E. coli</i> (APEC). Although the diguanylate cyclase DgcE (UniProt: P38097) is known to regulate virulence through c-di-GMP signaling, its potential as a therapeutic target has not been investigated.</p> Results <p>In this study, five female BALB/c mice were immunized to generate a monoclonal antibody. We developed an IgM monoclonal antibody (E11G12) targeting a defined region of DgcE and evaluated its ability to potentiate gentamicin activity. Structural prediction and docking analyses suggested specific binding interactions within the targeted DgcE region. In vitro checkerboard assays demonstrated synergistic activity between E11G12 and gentamicin (FICI ≤ 0.5), and time-kill assays showed enhanced bactericidal activity compared to monotherapy. Treatment was associated with reduced intracellular c-di-GMP levels and increased gentamicin accumulation.</p> Conclusion <p>These findings suggest that the E11G12-aminoglycoside combination exhibits synergistic anti-APEC activity, potentially through blocking virulence via DgcE inhibition and enhancing antibiotic efficacy in association with c-di-GMP suppression. This approach offers a novel therapeutic strategy against drug-resistant APEC infections.</p>

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An IgM monoclonal antibody targeting diguanylate cyclase DgcE potentiates gentamicin activity against avian pathogenic Escherichia coli through modulation of c-di-GMP signaling

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月1日

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  • Li Fangfang,
  • Nie Lianhua,
  • Wang haiyang,
  • Wang Zhihao,
  • Lian Liyan,
  • Hu Jiangang,
  • Jia yuanzheng,
  • Bao Yinli,
  • Han xiangan,
  • Wang haidong

摘要

Background

The combination of monoclonal antibodies with aminoglycosides represents a promising strategy to counter the increasing prevalence of aminoglycoside resistance in avian pathogenic E. coli (APEC). Although the diguanylate cyclase DgcE (UniProt: P38097) is known to regulate virulence through c-di-GMP signaling, its potential as a therapeutic target has not been investigated.

Results

In this study, five female BALB/c mice were immunized to generate a monoclonal antibody. We developed an IgM monoclonal antibody (E11G12) targeting a defined region of DgcE and evaluated its ability to potentiate gentamicin activity. Structural prediction and docking analyses suggested specific binding interactions within the targeted DgcE region. In vitro checkerboard assays demonstrated synergistic activity between E11G12 and gentamicin (FICI ≤ 0.5), and time-kill assays showed enhanced bactericidal activity compared to monotherapy. Treatment was associated with reduced intracellular c-di-GMP levels and increased gentamicin accumulation.

Conclusion

These findings suggest that the E11G12-aminoglycoside combination exhibits synergistic anti-APEC activity, potentially through blocking virulence via DgcE inhibition and enhancing antibiotic efficacy in association with c-di-GMP suppression. This approach offers a novel therapeutic strategy against drug-resistant APEC infections.