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High-throughput Assay to Phenotype Salmonella enterica Typhimurium Association, Invasion, and Replication in Macrophages
Published on: August 11, 2014
Interbacterial AI-2 signaling orchestrates chemotaxis, attachment, and antimicrobial peptide resistance to promote
Anmol Singh1, Abhilash Vijay Nair1, R S Rajmani2
1Department of Microbiology and Cell Biology, Division of Biological, Indian Institute of Science, Bengaluru, India.
Abstract:
Quorum sensing enables bacteria to coordinate collective behaviors crucial for survival and infection. Here, we show that Salmonella Typhimurium employs LuxS/autoinducer-2 (AI-2) signaling to regulate multiple stages of pathogenesis. AI-2 functions as a chemoattractant and modulates the expression of chemotaxis and motility-associated genes, promoting flagellar assembly and adhesion to the epithelial host cells. Loss of LuxS/AI-2 signaling diminishes hilD and SPI-1 gene expression, unveiling a regulatory link between quorum sensing and virulence determinants. Further, AI-2 signaling governs resistance to antimicrobial peptides through the pmrD/AB system and supports intracellular proliferation in the host cells. Transcriptomic profiling revealed that LuxS/AI-2 controls distinct gene networks spanning invasion, survival, and immune evasion. In murine infection models, inhibition of LuxS/AI-2 signaling in combination with antibiotics can be an alternative therapeutic approach. Our findings establish LuxS/AI-2 as an integrated regulatory hub in Salmonella pathogenesis and highlight quorum sensing as a targetable mechanism for therapeutic intervention.
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