Multi-Omics of Salmonella ArtAB Toxin Activity Reveals Early Transcriptomic Remodeling and Epithelial Barrier Dysfunction

ABSTRACT: AB5 toxins are important virulence factors produced by Gram-negative bacteria. These multi-subunit toxins have been identified in non-typhoidal Salmonella (NTS) strains; however, their characterization and mechanistic interactions with mammalian hosts remain poorly understood. One such toxin is ArtAB from Salmonella Typhimurium DT104, a multidrug resistant NTS strain. The cytotoxicity of ArtAB and equimolar concentrations of ArtB was evaluated in Chinese Hamster Ovary (CHO-K1) cells over 72 hours. At 4-hours post-treatment with ArtAB and ArtB, CHO cell host responses were characterized by RNA sequencing, quantitative proteomics, and qRT-PCR. ArtAB predominantly altered host transcriptional programs associated with inflammatory signaling, MAPK pathways, and cytoskeletal organization. In contrast, ArtB stimulated limited transcriptional responses, but more pronounced proteomic changes in vesicular trafficking and lysosomal proteins. Cytoskeletal remodeling pathways altered by ArtAB implicated a functional role in epithelial barrier dysfunction. This functional outcome was assessed in C2BBe1 intestinal epithelial cells using electric cell-substrate impedance sensing (ECIS). ECIS showed a significant reduction in paracellular resistance following ArtAB treatment. Together, these findings demonstrate that ArtAB remodels host signaling through non-cytolytic mecha-nisms and compromises epithelial barrier function, providing new insight into the role of NTS AB5 toxins in pathogenesis.

INSTRUMENT(S):

ORGANISM(S): Cricetulus Griseus (chinese Hamster) (cricetulus Barabensis Griseus)

TISSUE(S): Diploid Cell

DISEASE(S): Salmonellosis

SUBMITTER: Juliette Tinker  

LAB HEAD: Juliette K. Tinker

PROVIDER: PXD082171 | Pride | 2026-10-05

REPOSITORIES: Pride