2026-10-11T13:20:37Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33948937 2026-09-21T04:28:45Z category_303 portal_316 item_type_3 month_year_09_2026

Supplementary file 1_Salmonella typhimurium exploits macrophage-derived arginine as an intracellular signal for SPI-2 virulence gene activation.docx Xinyue Wang (286629) Shuai Ma (414625) Ting Ye (346594) Houliang Guo (20348893) Yiming Wang (163598) Xiaolin Yan (3796822) Yuyang Sun (596946) Mengjie Zhao (11219926) Lingyan Jiang (4063771) Lu Feng (193271) Clinical Microbiology arginine ArgR Salmonella typhimurium SPI-2 T3SS virulence regulation Background<p>Arginine contributes to host defense by serving as a substrate for inducible nitric oxide synthase (iNOS) to produce antimicrobial nitric oxide (NO). However, how bacterial pathogens respond to host arginine metabolism remains poorly understood.</p>Results<p>We found that Salmonella Typhimurium (S. Tm) infection causes arginine accumulation in macrophages. This accumulation is associated with two concurrent mechanisms: enhanced arginine import via upregulation of the CAT2 transporter, and pathogen-mediated suppression of host iNOS expression. S. Tm then exploits this accumulated arginine as an intracellular signal to upregulate virulence gene expression and promote its replication. Mechanistically, arginine activates the type III secretion system (T3SS) encoded by Salmonella pathogenicity island 2 (SPI-2) via the bacterial transcriptional regulator ArgR, which binds to the promoter of ssrA, the key regulator of SPI-2, in an arginine-dependent manner. Disruption of argR impairs S. Tm intracellular replication and attenuates virulence in mice.</p>Conclusions<p>These findings reveal that S. Tm co-opts the host’s arginine-mediated immune response by sensing macrophage-derived arginine as a signal to initiate its virulence program, revealing a pathogen adaptation strategy that links metabolic sensing to virulence activation.</p> 2026-09-21T04:28:45Z Dataset Dataset 10.3389/fcimb.2026.1877832.s001 https://figshare.com/articles/dataset/Supplementary_file_1_Salmonella_typhimurium_exploits_macrophage-derived_arginine_as_an_intracellular_signal_for_SPI-2_virulence_gene_activation_docx/33948937 CC BY 4.0