Different types of cell death induced by enterotoxins

Abstract

The infection of bacterial organisms generally causes cell death to facilitate microbial invasion and immune escape, both of which are involved in the pathogenesis of infectious diseases. In addition to the intercellular infectious processes, pathogen-produced/secreted enterotoxins (mostly exotoxins) are the major weapons that kill host cells and cause diseases by inducing different types of cell death, particularly apoptosis and necrosis. Blocking these enterotoxins with synthetic drugs and vaccines is important for treating patients with infectious diseases. Studies of enterotoxin-induced apoptotic and necrotic mechanisms have helped us to create efficient strategies to use against these well-characterized cytopathic toxins. In this article, we review the induction of the different types of cell death from various bacterial enterotoxins, such as staphylococcal enterotoxin B, staphylococcal alpha-toxin, Panton-Valentine leukocidin, alpha-hemolysin of Escherichia coli, Shiga toxins, cytotoxic necrotizing factor 1, heat-labile enterotoxins, and the cholera toxin, Vibrio cholerae. In addition, necrosis caused by pore-forming toxins, apoptotic signaling through cross-talk pathways involving mitochondrial damage, endoplasmic reticulum stress, and lysosomal injury is discussed.

Keywords: Panton-Valentine leukocidin; Shiga toxin; alpha-hemolysin; apoptosis; cholera toxin; cytotoxic necrotizing factor 1; enterotoxin; exotoxin; heat-labile enterotoxin; necrosis; pore-forming toxin; staphylococcal alpha-toxin; staphylococcal enterotoxin B.

Figure 1

In vitro infection of Uropathogenic E. coli (UPEC) causes apoptotic and necrotic cell death in human renal proximal tubular epithelial cells. Human renal proximal tubular epithelial cells (HK-2) were infected with or without clinical isolates of UPEC (MOI = 1) for 12 h. Annexin V (green), propidium iodide (PI, red), and Hoechst 33258 (blue) were used for apoptotic (solid arrowheads), necrotic (empty arrowheads), and nucleic acid staining, respectively, and analyzed by confocal microscopy. Stars indicate E. coli.