The toxin/antitoxin system

Most bacteria that colonise our environment pose no threat to us humans. However, a small number of additional bacterial genes are sufficient to transform an innocuous unicellular organism into a dangerous pathogen that is resistant to antibiotics

The majority of these “virulence factors” are transmitted from one bacterium to the next by so-called mobile genetic elements. This exchange of genes can take place even between species that, from an evolutionary point of view, are very far removed from one another, and is one of the main reasons for the rampant appearance of new multi-resistant germs.

Nevertheless, to gain these new advantages, the bacteria must often sign a pact with the devil. Because the mobile genetic elements are unstable and constantly risk being eliminated from the bacterial genome, e.g., during cell division, they contain toxin/antitoxin systems in addition to the virulence and resistance genes. These small DNA sections consist of only two genes that generate a fatal addiction. Once they are part of the bacterial genetic makeup, the bacterium starts to produce the two gene products of a toxin/antitoxin system: a strong toxic protein (‘toxin’) which threatens to poison the cell from within, and an ‘antitoxin’ which neutralises the toxin by interacting with it. While the antitoxin is present, the bacterium can initially continue to exist little affected by receiving a toxin/antitoxin system. However, the antitoxin molecules are perfidiously eliminated faster through the cellular degradation mechanisms than the toxin. The cells must therefore continue to synthesise the antitoxin in order to avoid poisoning by the toxin. If a cell loses the mobile genetic element with the toxin/antitoxin system, the production of the antitoxin is blocked. This causes the toxin to be released and leads to a ’programmed‘ bacterial cell death. The only cells able to survive are those possessing the mobile genetic elements containing the toxin/antitoxin system.

Thanks to this selection mechanism, the mobile genetic elements can avoid disappearing from the genetic makeup, even if the bacteria are not threatened by antibiotics. Even in the absence of the selection pressure exerted by antibiotics, they are maintained – together with any resistance genes – although they represent a potential threat to the cells. Toxin/antitoxin systems therefore have the potential to kill off bacteria, but could also be responsible for the stabilisation of resistance. Further study of these will be important in future research on antibiotics.

Recent evidence increasingly suggests that toxin/antitoxin systems have other selective advantages and have taken on further functions in the course of bacterial evolution. For instance, if a bacterial population is in danger of disappearing due to starvation, certain TA systems seem to provoke an ’altruistic‘ death of a subpopulation, in order to release nutrients and ensure the survival of the main bacterial population.

AM/HR

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