Host lipid sensing promotes invasion of cells with pathogenic Salmonella

Abstract

Pathogenic Salmonella species initiate infection by invading non-phagocytic intestinal epithelial cells (IEC). This invasion is brought about by a number of Salmonella invasion promoting molecules (Sips) encoded by the Salmonella Pathogenicity Island - 1 (SPI-1). Intracellular delivery of some of these molecules also brings about caspase-1 – mediated pyroptotic cell death that contributes to pathogen clearance. These molecules are secreted and delivered inside cells upon contact of Salmonella with one or more host signals whose identity has not been established. We show that lysophosphatidylcholine (LPC) released following activation of caspase-1 in Salmonella – infected cells and abundant in plasma amplifies production of Sips from this pathogen and promotes its cellular invasion. LPC brings about adenylate cyclase and cAMP receptor protein (CRP) - dependent de novo synthesis of SipC that is accompanied by its translocation to bacterial cell surface and release into the outside milieu. Treatment of Salmonella with LPC produces sustained induction of SPI - 1 transcriptional regulator, hilA. Our findings reveal a novel host lipid sensing - driven regulatory mechanism for Salmonella invasion.

Evasion of Plant Innate Defense Response by Salmonella on Lettuce

“…In contrast, cell free lysate (CFL) treatment to lettuce leaves from S. Typhimurium showed a classical MAMP based stomatal closure compared to live cell treatments, suggesting that cell free or secreted components from S. Typhimurium are recognized by plants to trigger innate response. The host sensing of cell free lysate from S. Typhimurium SL1344 was monitored and shown with human cells, wherein cell free lysates from S. Typhimurium SL1344 were recognized by the hosts leading to caspase-1-mediated proteolytic cell death contributing to pathogen clearance (Shivcharan et al, 2018). Interestingly, the heat-killed CFL treatment showed similar stomatal aperture as seen previously with live S. Typhimurium cells, suggesting that host sensing for innate stomatal defense requires secreted exo-metabolites.…”

Salmonella Pathogenicity Island 1 (SPI-1) and Its Complex Regulatory Network

“…The relatively high glucose concentration in the proximal small intestine can inhibit SPI-1 gene expression via Mlc, perhaps together with PhoBR and/or SirA (Agbor and McCormick, 2011). Lysophosphatidylcholine released following caspase-1 activation in Salmonella -infected cells promotes the expression of Sips and HilA and increases Salmonella invasion of host cells, and it is regarded as a key component of a novel regulatory mechanism for the regulation of cellular invasion with pathogenic Salmonella (Shivcharan et al, 2018).…”

Lysophosphatidylcholine Enhances Bactericidal Activity by Promoting Phagosome Maturation via the Activation of the NF-κB Pathway during Salmonella Infection in Mouse Macrophages

“…Recently, Shivcharan et al (2018) demonstrated that LPC promotes the invasive ability of Salmonella by enhancing the Salmonella invasion-promoting molecules spiA and spiC. In addition, LPC continuously maintains the expression of hilA, one of the major transcription factors of Sips.…”