New multipurpose on / off switch to control bacterial growth

Figure 1. Domain DUF4065 / Panacea is found in various TA-like loci across bacteria, archaea, and bacteriophages. The IQTree maximum likelihood tree branches of a typical PanA sequence are color coded by major taxonomic groups according to the upper left key with additional symbols to accentuate the bacteriophage. According to the key on the left, the outer and inner ring rectangles indicate the presence or absence of the N-terminal domain of the associated toxin group, which is predicted to be the PanA sequence, respectively. The colored circles between the rings show the estimated TA pairs tested in the toxicity neutralization assay and the results of those assays. “TA” means that expression of the toxin impairs the growth of E. coli, and co-expression of the antitoxin completely or partially counteracts the toxicity. “Toxic” means that toxicity has been confirmed, but the PanA sequence of the same family is not rescued by this E. coli system. A “cloning impasse” is when the plasmid cannot be subcloned by chemically synthesizing a putative toxin gene because it is too toxic. The gray circle on the branch indicates branch support with the IQTree ultra-fast bootstrap (53). Tree annotations were performed using iTOL (54). Credit: DOI: 10.1073 / pnas.2102212119

Lund researchers have discovered an antitoxin mechanism that can neutralize hundreds of different toxins and may protect bacteria from viral attack. This mechanism was named panacea after the Greek goddess of medicine, whose name became synonymous with universal remedies. Understanding the mechanisms of bacterial toxins and antitoxins is crucial to the future success of so-called phage therapy for the treatment of antibiotic-resistant infections, researchers say.The study is published at PNAS..

The so-called toxin-antitoxin system, a type of on / off switch in the DNA genome of many bacteria, is increasingly being found to protect. Bacteria Against attacks by bacteriophage (a virus that infects bacteria). Activation of the toxin allows the bacterial population to enter a sort of blockade that limits growth and thus limits the spread of the virus. Therefore, understanding the diversity, mechanisms, and evolution of these systems is difficult. Phage therapy To treat antibiotic-resistant infections.

“The toxin-antitoxin pair is made up of genes that code for toxins that dramatically inhibit. Bacterial growth Adjacent genes encoding antitoxins that counteract toxic effects. It’s like putting a bottle of poison on the shelf next to the bottle of antidote. Toxin-antitoxin pairs were previously seen to evolve to bind to new toxins and antitoxins, but the scale of neutralizing capacity found in panacea, the so-called hyperpromise cui, is unprecedented. ” Explains Gemma Atkinson, a researcher and group leader at Lund University.Lead research

PhD student and co-lead author Chayan Kumar Sahamade has created a computer program to analyze the types of genes found adjacently in the bacterial genome. The team then used this tool to predict new antitoxin genes next to some of the very powerful toxins they worked on earlier.

Researchers were surprised to find that the folding of certain antitoxin proteins was found in toxin-antitoxin-like sequences containing dozens of toxins. Many of these toxins are new to science. Another lead author, Tatsuaki Kurata of Lund University, has experimentally confirmed that some of these systems are genuine toxins neutralized by adjacent antitoxin genes.

This study is probably just the tip of the iceberg to know about the diversity of toxin-antitoxin systems, and there may be a range of similar systems that were previously under radar. Is shown.

Not only is it important to understand the biochemistry of bacteria, but the discovery of new toxin-antitoxin systems is the so-called Phage Treatment for antibiotic-resistant infections. As bacteria become more and more resistant to antibiotics, other approaches are needed to eliminate the infection.

The principle of phage therapy is to treat patients with a cocktail of bacteriophage (a virus that infects bacteria) to kill the bacteria that cause the infection. However, bacteria have various defense systems to protect themselves from phages, including the toxin-antitoxin system.

“Therefore, identifying the pathogen’s toxin-antitoxin system may help in the future design of phage therapy that can counter this defense layer,” explains Gemma Atkinson.

So what is the next research step? “We are currently trying to find new toxin-antitoxin systems on a universal scale and understand their involvement in phage defense, and that we can think of the toxin-antitoxin system as on-. Given that, we are also interested in possible bioengineering applications of the toxin-antitoxin system. Switch off core aspects of bacteriophage. A full set of toxin-antitoxin systems fine-tunes bacterial metabolism. , Could be a molecular toolbox for controlling bacterial cell resources. This is of interest to bacteria. ”

Newly discovered toxins abundant in unicellular organisms-antitoxin system

For more information:
Tatsuaki Kurata et al., Indiscriminate antitoxin protein domain for neutralizing various toxin domains, Minutes of the National Academy of Sciences (2022). DOI: 10.1073 / pnas.2102212119

Provided by
Lund University

Quote: A new multipurpose on / off switch for suppressing bacterial growth (February 9, 2022) https: // Obtained from February 9, 2022.

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New multipurpose on / off switch to control bacterial growth

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