Traditionally, programmed cell death (PCD) is associated with eukaryotic multicellular organisms. However, recently, PCD systems have also been observed in bacteria. Here we review recent research on two kinds of genetic programs that promote bacterial cell death. The first is mediated by mazEF, a toxin–antitoxin module found in the chromosomes of many kinds of bacteria, and mainly studied in Escherichia coli. The second program is found in Bacillus subtilis, in which the skf and sdp operons mediate the death of a subpopulation of sporulating bacterial cells. We relate these two bacterial PCD systems to the ways in which bacterial populations resemble multicellular organisms.

▪ Abstract In bacteria, programmed cell death is mediated through “addiction modules” consisting of two genes. The product of the second gene is a stable toxin, whereas the product of the first is a labile antitoxin. Here we extensively review what is known about those modules that are borne by one of a number of Escherichia coli extrachromosomal elements and are responsible for the postsegregational killing effect. We focus on a recently discovered chromosomally borne regulatable addiction module in E. coli that responds to nutritional stress and also on an antideath gene of the E. coli bacteriophage λ. We consider the relation of these two to programmed cell death and antideath in bacterial cultures. Finally, we discuss the similarities between basic features of programmed cell death and antideath in both prokaryotes and eukaryotes and the possibility that they share a common evolutionary origin.

mazEF is an Escherichia coli suicide module specific for a stable toxin and a labile antitoxin. Inhibiting mazEF expression appeared to activate the module to cause cell death. Here we show that several stressful conditions, including high temperatures, DNA damage, and oxidative stress, also induce mazEF -mediated cell death. We also show that this process takes place only during logarithmic growth and requires an intact relA gene.

mazEF is a toxin-antitoxin module located on many bacterial chromosomes, including those of pathogens. Here, we report that Escherichia coli mazEF -mediated cell death is a population phenomenon requiring a quorum-sensing molecule that we call the extracellular death factor (EDF). Structural analysis revealed that EDF is a linear pentapeptide, Asn-Asn-Trp-Asn-Asn. Each of the five amino acids of EDF is important for its activity.