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Volume 172, Issue 1

The glucose uptake inhibitor SgrS is induced by D-serine yet does not contribute to growth arrest in enterohaemorrhagic Open Access

Abstract

Bacterial pathogens sense and respond to host-derived metabolites to regulate virulence and establish successful infections. -Serine, an amino acid abundant in some extraintestinal environments but scarce in the intestine, functions as a key niche-specific signal that influences the tissue tropism of different pathotypes. In enterohaemorrhagic , a major foodborne pathogen causing severe human disease, -serine exposure triggers significant transcriptional changes distinct from those seen in extraintestinal pathotypes. Recent publication of our extensive -serine pathotype transcriptome data on the open database MORF included genome reannotation. This revealed the previously unannotated small regulatory RNA SgrS as being the most significantly upregulated transcript in response to -serine exposure. Despite its canonical role in managing glucose-phosphate stress by inhibiting glucose uptake, here, we show that -serine-mediated growth inhibition occurs independently of SgrS and extends beyond glucose metabolism, affecting growth across diverse carbon sources with varying transport mechanisms. Growth inhibition persisted following the deletion of and could not be alleviated by pyruvate or pantothenate supplementation, while -serine provided partial rescue, suggesting disruption of fundamental metabolic processes. The novel observation that -serine induces SgrS suggests a wider regulatory role beyond managing glucose phosphate stress during impeded glycolysis. Moreover, we describe key distinctions between -serine toxicity in EHEC and previous reports with laboratory strains, highlighting the importance of strain-specific metabolic and regulatory architecture in response to host-associated cues.

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Keyword(s): E. coli , metabolism , regulation , small RNA , stress response and transporter
Funding
This study was supported by the:
  • Health Research Board (Award EIA-2024-005)
    • Principal Award Recipient: O'BoyleNicky
© 2025 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2026-01-09
2026-01-19

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/content/journal/micro/10.1099/mic.0.001648
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The glucose uptake inhibitor SgrS is induced by D-serine yet does not contribute to growth arrest in enterohaemorrhagic Escherichia coli
Microbiology 172, 001648 (2026); https://doi.org/10.1099/mic.0.001648
/content/journal/micro/10.1099/mic.0.001648
/content/journal/micro/10.1099/mic.0.001648
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