A Flexible and Deadly Way to Control Salmonella Infection

Abstract

Although programmed cell death can control intracellular bacterial replication, the role of cell death during systemic Salmonella infection remained elusive. In this issue of Immunity, Doerflinger et al. discover a critical but overlapping role for cell death associated caspases during Salmonella infection.Programmed cell death is one mechanism by which the host controls intracellular pathogen replication, in part by eliminating the replicative niche (Miao et al., 2010). Salmonella enterica serovar Typhimurium (S. Typhimurium) is an important intracellular Gram-negative bacterial pathogen that primarily infects phagocytes and can cause typhoid fever, a systemic infection that affects 10-20 million people globally (Kupz et al., 2014). One form of cell death referred to as ''pyroptosis'' is induced in phagocytes infected with S. Typhimurium through inflammasome-dependent activation of caspase-1 or lipopolysaccharide-induced activation of caspase-11 (Broz et al., 2010). Caspase-1 or caspase-11 can process gasdermin D (GSDMD), which self assembles into a pore that inserts into the plasma membrane resulting in pyroptosis (Negroni et al., 2015) (Figure 1, upper left). Casp1 À/À Casp11 À/À macrophages resist S. Typhimurium induced cell death in vitro (Broz et al., 2012), suggesting pyroptosis contributes to cell death during S. Typhimurium infection. However, in a model for the systemic phase of typhoid fever where mice are infected with an attenuated strain of S. Typhimurium intravenously, Casp1 À/À Casp11 À/À mice are still able to clear the infection by 12 weeks post-infection (Doerflinger et al., 2020;Kupz et al., 2014). Additional deletion of the close homolog caspase-12 also had no added effect on clearance of S. Typhimurium. This suggests that either cell death is not required for control of S. Typhimurium in this model or that alternative programmed cell death pathways compensate for the loss of pyroptosis. Indeed, in this issue of Immunity (Doerflinger et al., 2020), Doerflinger et al. find that

Novel phenolic compound from Southern Ocean microalgae Chlorella sp. PR-1 and its antibacterial activity

“…PR-1 is the biocide that showed promising antibacterial action to S. typhimurium. The likely mechanism by which the growth of S. typhimurium was inhibited is phenol-induced pyroptosis and apoptosis involving flexible deployment of caspases (Kinsella & Stallings 2020). S. typhimurium is susceptible to OH group of the phenols that act as a proton exchanger reducing the pH gradient across the cell membrane and thus leading to cell death.…”