Metabolic flux analysis revealed key roles of ArcB
in ADI pathway and IlvC in BCAA biosynthesis during Streptococcus suis anaerobic growth and infection
in ADI pathway and IlvC in BCAA biosynthesis during Streptococcus suis anaerobic growth and infection
Author(s)
Type
Journal Article
Abstract
Critical metabolic enzymes and pathways specific to bacterial adaptation in different host microenvironments directly contribute to bacterial pathogenicity. In this study, a virulent strain of the important zoonotic pathogen Streptococcus suis was found to show enhanced growth under anaerobic conditions compared to aerobic conditions. Transcriptomic analysis found a significant suppression of many central metabolic genes during anaerobic growth of S. suis. The transcriptomic data were used to reconstruct a genome-scale metabolic network to assess the distribution of metabolic fluxes in S. suis under different conditions. Significant activation of the arginine deiminase (ADI) and branched-chain amino acid (BCAA) biosynthesis pathways was identified. Gene deletion mutants of arcB and ilvC participating in these two pathways, respectively, were constructed. Compared to the wild-type strain, the ΔarcB mutant showed more significant growth deficiency under anaerobic conditions than under aerobic conditions. Accumulation of ATP and NH3, the metabolites of the ADI pathway, was significantly higher when S. suis was cultured under anaerobic conditions, and this effect was attenuated in the ΔarcB mutant. The knockout of IlvC of the BCAA pathway disrupted the normal growth of S. suis in valine- and isoleucine-limited medium under anaerobic conditions. Both ΔarcB and ΔilvC showed attenuation in mice with decreased lethality, bacterial loads in tissues, and cytokine levels in serum, with the hypoxia-induced gene up-regulated in tissues. Therefore, ADI and BCAA pathways are critical for S. suis survival in response to hypoxia and infection in vivo, with ArcB and IlvC being promising drug targets.
Date Issued
2026-12-01
Date Acceptance
2025-12-06
Citation
Virulence, 2026, 17 (1)
ISSN
2150-5594
Publisher
Informa UK Limited
Journal / Book Title
Virulence
Volume
17
Issue
1
Copyright Statement
© 2025 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41369137
Subjects
Environmental adaptation
Genome-scale metabolic networks (GSMMs)
amino acid metabolism
anaerobic growth
streptococcus suis
Publication Status
Published
Coverage Spatial
United States
Article Number
2602281
Date Publish Online
2025-12-14