A new multipurpose on-off switch for inhibiting bacterial growth

Date:
February 8, 2022
Source:
Lund University
Summary:
Researchers have discovered an antitoxin mechanism that seems
to be able to neutralize hundreds of different toxins and may
protect bacteria against virus attacks. The mechanism has been
named Panacea, after the Greek goddess of medicine whose name
has become synonymous with universal cure. The understanding of
bacterial toxin and antitoxin mechanisms will be crucial for the
future success of so-called phage therapy for the treatment of
antibiotic resistance infections, the researchers say.



FULL STORY ========================================================================== Researchers in Lund have discovered an antitoxin mechanism that seems
to be able to neutralise hundreds of different toxins and may protect
bacteria against virus attacks. The mechanism has been named Panacea,
after the Greek goddess of medicine whose name has become synonymous
with universal cure. The understanding of bacterial toxin and antitoxin mechanisms will be crucial for the future success of so-called phage
therapy for the treatment of antibiotic resistance infections, the
researchers say. The study has been published in PNAS.


========================================================================== So-called toxin-antitoxin systems, a kind of on-off switch in
many bacterial DNA genomes, are increasingly being found to defend
bacteria against attack by bacteriophages -- viruses that infect
bacteria. Activation of toxins allows bacterial populations to go into
a kind of lockdown that limits growth and therefore the spread of the
virus. As such, understanding the diversity, mechanisms and evolution
of these systems is critical for the eventual success of phage therapy
to treat antibiotic resistance infections. -- Toxin-antitoxin pairs
consist of a gene encoding a toxin that dramatically inhibits bacterial
growth and an adjacent gene encoding an antitoxin that counteracts the
toxic effect. It is like keeping a bottle of poison on a shelf next to
a bottle of the antidote. While toxin-antitoxin pairs have been seen to
evolve to associate with new toxins or antitoxins before, the scale of the neutralisation ability seen with Panacea -- so called hyperpromiscuity --
is unprecedented, explains researcher and group leader Gemma Atkinson
at Lund University, who has led the study.

PhD student and co-first author Chayan Kumar Saha made a computer program
for analysing the kinds of genes that are found next to each other in
bacterial genomes. The team then used this tool to predict new antitoxin
genes found next to some very potent toxins that they have previously
worked on. "We were startled by the discovery that one particular
antitoxin protein fold can be found in toxin-antitoxin-like arrangements
with dozens of different kinds of toxins. Many of these toxins are new
to science." The other first author Tatsuaki Kurata, Lund University,
has confirmed experimentally that several of these systems are genuine
toxins neutralized by the neighbouring antitoxin genes.

The study shows that what we know so far about the diversity of
toxin-antitoxin systems probably is just the tip of the iceberg, and
that there could be a range of similar systems that have gone under the
radar until now. -- As well as being important for understanding the
weird and wonderful world of bacterial biochemistry, the discovery of new toxin-antitoxin systems is important for so- called phage therapy against antibiotic resistant infections. As bacteria have increasingly become
resistant to antibiotics, other approaches are needed for eliminating infections.

The principle of phage therapy is to treat patients with cocktails of bacteriophages -- viruses that infect bacteria -- in order to kill the
bacteria causing infection. However bacteria carry various defence systems
to protect themselves from phages, and this includes toxin-antitoxin
systems.

"Thus identifying toxin-antitoxin systems of pathogens may help us in
the future design phage therapy that can counter this layer of defence," explains Gemma Atkinson.

So, what is the next research step? "We are now trying to find novel toxin-antitoxin systems on a universal scale, and understand their
involvement in phage defence. We are also interested in possible biotechnological applications of toxin-antitoxin systems, given that
these systems can be thought of as on-off switches of core aspects of
bacterial biology. The full set of toxin-antitoxin systems could be
a molecular toolbox for tweaking bacterial metabolism and controlling
bacterial cell resources.

This can be important in industrial and pharmaceutical manufacture
situations where bacteria are used to produce molecules of interest." ========================================================================== Story Source: Materials provided by Lund_University. Original written
by Agata Garpenlind.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Tatsuaki Kurata, Chayan Kumar Saha, Jessica A. Buttress, Toomas
Mets,
Tetiana Brodiazhenko, Kathryn J. Turnbull, Ololade F. Awoyomi,
Sofia Raquel Alves Oliveira, Steffi Jimmy, Karin Ernits, Maxence
Delannoy, Karina Persson, Tanel Tenson, Henrik Strahl, Vasili
Hauryliuk, Gemma C.

Atkinson. A hyperpromiscuous antitoxin protein domain for the
neutralization of diverse toxin domains. Proceedings of the
National Academy of Sciences, 2022; 119 (6): e2102212119 DOI:
10.1073/ pnas.2102212119 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220208105241.htm
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