Cadaverine prevents the escape of Shigella flexneri from the phagolysosome: A connection between bacterial dissemination and neutrophil transepithelial signaling

Shigella flexneri causes bacillary dysentery in humans by invading epitheli al cells of the colon, which is characterized by an acute polymorphonuclear leukocyte (PMNL)-rich inflammation. Our recent studies demonstrated that c adaverine, a polyamine, specifically acts to abrogate transepithelial signa ling to PMNL induced by S. flexneri. Here, insight is provided into the cel lular mechanisms by which cadaverine attenuates the ability of Shigella spe cies to induce PMNL signaling. It was found that cadaverine retards the lys is of the Shigella species-containing vacuole, suggesting that a blockade i s established, in which the pathogen is prevented from adequately interacti ng with the cytoskeleton. Furthermore, an IcsA mutant of S. flexneri that c annot interact with the cytoskeleton and spreads intercellularly fails to i nduce transmigration of PMNL. Results indicate that cadaverine-induced comp artmentalization of Shigella species to the phagolysosome might be a protec tive response of the host that directly contributes to the diminished abili ty of PMNL to transmigrate across model intestinal epithelia.