Bacterial toxin-antitoxin systems: more than selfish entities?

Abstract

Bacterial toxin-antitoxin (TA) systems are diverse and widespread in the prokaryotic kingdom. They are composed of closely linked genes encoding a stable toxin that can harm the host cell and its cognate labile antitoxin, which protects the host from the toxin's deleterious effect. TA systems are thought to invade bacterial genomes through horizontal gene transfer. Some TA systems might behave as selfish elements and favour their own maintenance at the expense of their host. As a consequence, they may contribute to the maintenance of plasmids or genomic islands, such as super-integrons, by post-segregational killing of the cell that loses these genes and so suffers the stable toxin's destructive effect. The function of the chromosomally encoded TA systems is less clear and still open to debate. This Review discusses current hypotheses regarding the biological roles of these evolutionarily successful small operons. We consider the various selective forces that could drive the maintenance of TA systems in bacterial genomes.

Figure 1. Advantage conferred by plasmid-encoded TA systems.

(A) Vertical transmission. TA systems increase plasmid prevalence in growing bacterial populations by post-segregational killing (PSK). PSK⁺ plasmid is shown in purple, left panel. Daughter bacteria that inherit a plasmid copy at cell division grow normally. If daughter bacteria do not inherit a plasmid copy, degradation of the labile antitoxin proteins by the host ATP-dependent proteases will liberate the stable toxin. This will lead to the selective killing of the plasmid-free bacteria (in gray). When considering only vertical transmission, TA systems increase the prevalence of the plasmid in the population as compared with plasmids devoid of TA systems (PSK⁻ plasmid in black, right panel). (B) Horizontal transmission. Plasmid–plasmid competition. The PSK⁺ plasmid (in purple) and the PSK⁻ plasmid (in black) belong to the same incompatibility group and are conjugative. Under conditions in which conjugation occurs, conjugants containing both plasmids are generated. Because the two plasmids are incompatible, they can not be maintained in the same bacteria. The “loss” of the PSK⁺ plasmid will lead to the killing of bacteria containing the PSK⁻ plasmid through the PSK mechanism (in gray), thereby outcompeting the PSK⁻ plasmid. On the contrary, the loss of the PSK⁻ plasmid will be without any deleterious effect on the PSK⁺ plasmid. Through multiple events of conjugation, the fitness of the PSK⁺ plasmid will be increased (arrow).

Figure 2. The anti-addiction model.

The chromosomally encoded anti-addiction system is represented in black; the PSK⁺ plasmid in purple. In this model, the antitoxin of the chromosomally encoded TA system is able to counteract the toxin of the plasmid-encoded system. Therefore, daughter bacteria that do not inherit a plasmid copy at cell division will survive post-segregational killing.