ANTIBIORESISTANCE: An aberrant protein that kills bacterial cells

Because the protein is really deadly for bacterial cells. Scientists describe how this ‘mistakenly’ designed protein mimics the action of aminoglycosides, a class of antibiotics. The protein could also serve as a model for a new class of antibiotics.

A new strategy to control bacterial growth

A chance discovery: The Brookhaven team, which specializes in energy research, was initially far removed from human health and used “only” E. coli bacteria to study the genes involved in building the cell wall of plants with the aim of converting plant material (biomass) into biofuels more efficiently. While activating the expression of a specific plant gene that allows bacteria to make the protein in question, the researchers found that the protein stopped cell growth entirely: “This protein had an extremely toxic effect on the cells.

All cells died within minutes of activation of gene expression.

A welcome discovery: This discovery could provide a piece of the puzzle to bring the answer to antibiotic resistance. “Being able to control the formation of these bacteria is becoming increasingly important,” explains lead author Paul Freimuth, a biologist at the Brookhaven Institute: “Many scientists fear the widespread epidemics caused by these antibiotic-resistant superbugs”

  1. Understanding the Antibiotic Mechanism: By identifying this protein, which alone is able to mimic the effects of a complex mixture of aberrant proteins produced during treatment with aminoglycoside antibiotics, the team gains a new way to observe a mechanism that kills bacterial cells. In fact, the study shows that the protein itself is not the toxic factor, it is a strand of amino acids, part of the protein, “abnormal” because it is erroneously produced by the ribosomes of the bacterium that has this effect. The mechanism is reminiscent of that of aminoglycosides, which force ribosomes to make similar “phasing” errors when building proteins.
  • One protein is enough: “If a bacterial cell has 50,000 ribosomes, each of which produces a different aberrant protein, is the toxic effect the result of a specific aberrant protein or a combination of several?” This question, which has been debated for decades, has never been resolved,” the researchers say. So, almost by accident, this new work shows that a single aberrant protein can be enough to exert this toxic effect on bacterial cells.
  • How does the protein develop its toxic effect? During the production of the abnormal protein, the initial protein quality control step is activated well, but the later stages of the process necessary for the degradation of the abnormal proteins are blocked. Furthermore, it is the speed of production of the faulty protein that enables cell death: if the cells contain many copies of the gene that codes for the faulty plant protein, the cellular quality control machinery correctly detects the irregularity of the protein but cannot break it all the way down Conversely, if the number of copies of the gene encoding the protein is reduced, the cell’s quality control system manages to eliminate the toxic protein and the bacterial cells survive. The process is very similar to that observed in cells treated with sublethal doses of aminoglycoside antibiotics. If the dose is insufficient, the cellular quality control response will be activated, but not enough and the cells can still grow.
  1. Development of a new family of inhibitors the second goal of the team is to be able to reproduce this effect of the d-protein on the cell: “The next step will be to determine the structures of our protein, how it communicates with membrane channels and kills bacterial cells in order to develop new drugs with similar effects.”

#ANTIBIORESISTANCE #aberrant #protein #kills #bacterial #cells

Leave a Comment

Your email address will not be published.