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The killer within: A novel bacterial suicide mechanism

Date:
March 23, 2011
Source:
Public Library of Science
Summary:
The zeta toxins are a family of proteins that are normally present within various pathogenic bacteria and can mysteriously trigger suicide when the cells undergo stress. Researchers in Germany have now found the mechanism underlying this programmed bacterial cell death.

The zeta toxins are a family of proteins that are normally present within various pathogenic bacteria and can mysteriously trigger suicide when the cells undergo stress. A team led by Anton Meinhart at the Max Planck Institute for Medical Research in Heidelberg has now found the mechanism underlying this programmed bacterial cell death.

Their paper, publishing in the online, open access journal PLoS Biology, reports that zeta toxins convert a compound required for bacterial cell wall synthesis into a poison that kills bacteria from within. In the future it may be possible to hijack this mechanism for bacterial defense and to design drugs that mimic these toxins

Most bacteria harbor toxin-antitoxin (TA) systems, in which a bacterial toxin lies dormant under normal conditions, prevented from being active by its antitoxin counterpart. As long as the antitoxin is present, the bacterium can continue to exist and is not affected by the TA system. Under conditions of stress, however, the antitoxin is degraded, freeing the toxin to attack its host from within. Although the family of zeta toxins was discovered almost 20 years ago, their deadly mechanism has been enigmatic until now.

The first author on the paper, Hannes Mutschler, and his colleagues studied the molecular mechanism of action of the zeta toxin PezT from the PezAT (Pneumococcal epsilon zeta Antitoxin Toxin) system using the model bacterium Escherichia coli. The PezAT system is found in the major human pathogen Streptococcus pneumoniae -- a bacterium that causes serious infections such as pneumonia, septicaemia and meningitis. Bacterial cells in which PezT was activated showed symptoms of poisoning similar to the effects of penicillin. This involved first stalling in the middle of their division stage, and later the intersection zone between the two cell bodies burst and the cells died. The team showed that PezT and other zeta toxins are novel enzymes that transform the essential sugar building block UNAG (UDP-N-acetylglucosamine) into a toxic molecule. This molecule (UNAG-3P) inhibits the growth of the bacterial cell wall, causing the cells to burst and die.

The findings also enabled the scientists to explain a hitherto paradoxical phenomenon; namely, that the supposedly lethal activity of pneumococcal zeta toxin PezT can eventually boost the pneumococcal infection rate of the entire attacking cellular population. The activation of PezT actively causes individual bacteria to burst and release their cell contents. However, other individuals, which are metabolically less active, can survive the toxin's activity to some extent. In this process, the accelerated release of bacterial venoms by a subpopulation supports the surviving cells in their attack on the immune system during infection. It therefore seems that individual pneumococci altruistically sacrifice themselves during infection for the good of the overall population.

"UNAG-3P is a valuable lead-compound for the development of new broad-band antibiotics," says Meinhart, "since it will kill most rapidly growing bacteria." Thus, knowlege of the mechanism of zeta toxins could bring research on antibiotics a major step forward in the battle against bacterial resistance.


Story Source:

The above story is based on materials provided by Public Library of Science. Note: Materials may be edited for content and length.


Journal Reference:

  1. Hannes Mutschler, Maike Gebhardt, Robert L. Shoeman, Anton Meinhart. A Novel Mechanism of Programmed Cell Death in Bacteria by Toxin–Antitoxin Systems Corrupts Peptidoglycan Synthesis. PLoS Biology, 2011; 9 (3): e1001033 DOI: 10.1371/journal.pbio.1001033

Cite This Page:

Public Library of Science. "The killer within: A novel bacterial suicide mechanism." ScienceDaily. ScienceDaily, 23 March 2011. <www.sciencedaily.com/releases/2011/03/110322172215.htm>.
Public Library of Science. (2011, March 23). The killer within: A novel bacterial suicide mechanism. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2011/03/110322172215.htm
Public Library of Science. "The killer within: A novel bacterial suicide mechanism." ScienceDaily. www.sciencedaily.com/releases/2011/03/110322172215.htm (accessed October 20, 2014).

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