Programmed Cell Death in Bacteria

PROGRAMMED CELL DEATH IN BACTERIA

Although apoptosis has not been seen in single-celled organisms, a genetic system that kills Escherichia coli when under extreme stress does exist. Morphologically, the death does not resemble apoptosis, but like apoptosis, the death system is genetically encoded. In E. coli , an addiction module of two genes controls the death-inducing system ( Fig. 20.22 ). One gene encodes a toxin, MazF, which is quite stable. The second gene encodes the antitoxin, MazE, which prevents the toxin from killing the bacteria. The antitoxin is unstable and degrades very fast after translation. If its transcription or translation is stopped or slowed in any way, the level of antitoxin plummets and the toxin kills the bacteria.

The MazF toxin is a specific endoribonuclease that degrades messenger RNA. It recognizes the sequence ACA and cleaves to the 5′-side. Such enzymes have been named mRNA interferases and have now been found in a variety of bacteria. The net result is thedestruction of mRNA followed by a halt in protein synthesis. Cell death rapidly follows.

When bacteria are depleted of nutrients, transcription and translation slow down, and this may trigger the MazEF suicide system. Perhaps some E. coli commit suicide for the good of the rest, because the proteins, lipids, and nucleic acids of the dead cell could provide food for nearby cells. Despite being unicellular, bacteria have genetic programs for the good of the population. Another theory is that the MazEF suicide system is designed to limit the multiplication of bacterial viruses. Indeed, mutants of E. coli deleted for the whole mazEF operon give higher yields of bacteriophage when they burst. In wild-type cells, the MazEF system kills the cell before virus replication is complete and thus reduces the number of viruses produced.

Addiction modules also exist in bacteriophages such as P1 and lambda that are maintained in a lysogenic state. The toxin/antitoxin pair of proteins prevents the bacteriophage genome from being destroyed or lost during E. coli growth. The bacteriophage genome encodes both the toxin and the antitoxin. Just as in the MazEF system, the toxin protein is very stable, whereas the antitoxin degrades quickly and must be produced continually. If the P1 or lambda genome is lost, the stable toxin protein will kill the bacteria. Interestingly, the toxin produced by P1 does not kill E. coli directly but acts by activating the bacterium’s own MazEF system ( Fig. 20.23 ). The P1 toxin inhibits translation of the MazE antitoxin, which activates the MazF toxin, which in turn kills the cell.