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<p>The rise in antimicrobial resistance underscores the need for innovative strategies to combat gastrointestinal infections. Probiotics such as <i>Escherichia coli</i> Nissle 1917 (EcN) offer promising options, but the molecular mechanisms underlying their protective effects remain unclear. We introduce a G66R point mutation in FimH, creating a high-binding EcN variant that more effectively prevents <i>Salmonella</i> Typhimurium attachment and induces a distinct host transcriptional profile, shifting toward adaptive rather than innate inflammatory signaling. In vivo, EcN<sup>G66R</sup> pretreatment significantly reduced intestinal colonization, fecal shedding, and systemic spread, and prevented splenic enlargement compared with EcN<sup>WT</sup>. Protection was associated with a marked expansion of CD4<sup>+</sup> and CD8<sup>+</sup> T cells, essential for clearing intracellular pathogens. EcN<sup>G66R</sup> further enhanced “readiness” in the spleen under non-infected conditions, without adverse effects on host physiology. EcN<sup>G66R</sup> thus functions as a dual-action probiotic—improving competitive exclusion while priming cytotoxic T-cell-mediated protection—and provides a promising platform for developing next-generation microbe-based therapies.</p><p></p>

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Genetically engineered probiotic E. coli Nissle 1917 enhances protection against Salmonella via increased adhesion and systemic T-cell responses

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月21日

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  • Ewa Carolak,
  • Joanna Czajkowska,
  • Wiktoria Waszczuk,
  • Agata Dutkiewicz,
  • Anna Ewa Kedzierska,
  • Krzysztof Grzymajlo

摘要

The rise in antimicrobial resistance underscores the need for innovative strategies to combat gastrointestinal infections. Probiotics such as Escherichia coli Nissle 1917 (EcN) offer promising options, but the molecular mechanisms underlying their protective effects remain unclear. We introduce a G66R point mutation in FimH, creating a high-binding EcN variant that more effectively prevents Salmonella Typhimurium attachment and induces a distinct host transcriptional profile, shifting toward adaptive rather than innate inflammatory signaling. In vivo, EcNG66R pretreatment significantly reduced intestinal colonization, fecal shedding, and systemic spread, and prevented splenic enlargement compared with EcNWT. Protection was associated with a marked expansion of CD4+ and CD8+ T cells, essential for clearing intracellular pathogens. EcNG66R further enhanced “readiness” in the spleen under non-infected conditions, without adverse effects on host physiology. EcNG66R thus functions as a dual-action probiotic—improving competitive exclusion while priming cytotoxic T-cell-mediated protection—and provides a promising platform for developing next-generation microbe-based therapies.