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The structure that gives bacteria resistance to drugs has been identified

A research team from Iowa State University has deciphered the crystal structure of transport pumps that remove heavy metal toxins from bacteria, a mechanism that allows them to develop resistance to antibiotic drugs.

The proposed route of the metal transfer in the investigated pump.
The proposed route of the metal transfer in the investigated pump.

The lead researcher, a professor of chemistry, physics, astronomy, biochemistry, biophysics and molecular biology at the US Department of Energy (Ames Laboratories), said the findings provide researchers with better insights into the mechanism of bacterial resistance to antibiotics. Ultimately, the research could help drug researchers develop new and effective treatments against this resistance.

In order to achieve their findings, the researchers purified and synthesized the membrane proteins that make up the unit known as the efflux pump (non-specific pumps that are activated after exposure to an antimicrobial substance and transport it out) of the bacterium Escherichia coli. The researchers prepared several samples that contained the toxic heavy metals copper and silver and several samples without these metals.

The researchers used X-ray crystallography to compare the different structures, to identify the differences between them and to understand the mechanism responsible for the removal of heavy metal toxins from the cells.

Their paper specifically describes the crystal structure of the CusA unit, one of three parts of the pump responsible for removing toxins from the bacterium. The researcher explains that this unit is an internal transfer membrane that belongs to a wider superfamily of proteins (resistance-nodulation-division protein). It consists of 1047 amino acid units and surrounds the inner membrane 12 times.

The researcher explains: "The pumps identify and actively remove these substances from the bacterial cells, thus allowing them to survive in conditions of extreme toxicity."

"This study reports for the first time ever the detailed structure of a unique heavy-hitting transfer pump that allows bacteria to survive despite the toxic effects of copper and silver," explains one of the research partners. "By describing in detail the exact steps that the metal ion is expected to go through on its way through this transfer channel, this study provides us with ideas on how to block this path and thereby increase the sensitivity of harmful bacteria to heavy metal toxins."

The lead researcher, who has been studying the resistance of bacteria to antibiotics for about a decade, said that direct information about the ability of bacteria to resist heavy metal toxins is important information for biomedical research.

"We are interested in understanding the mechanisms of activity of these heavy metal pumps," he notes. "And this understanding could allow biotechnology researchers to develop more effective inhibitors that would block the pump's activity, and consequently reduce or even eliminate the bacteria's resistance to drugs."
The research findings were published in the prestigious journal Nature.

The news about the study

2 תגובות

  1. 1) Formation of membrane proteins is always problematic because the crystal is inherently suitable for determining the structure of water-soluble proteins.
    2) In addition, all these proteins have both a soluble side and a water-insoluble side, so it is problematic to simulate such conditions in a crystal
    3) "Just" from determining a molecular structure it is not possible to understand much and explanations for the protein's activity must be found by synthesizing the structural data with the results of biochemical characterization
    4) There are many theories and many measurement methods that assume that the main "interest" in protein conformations derives from the changes in the spatial structure and not precisely from the structure in the crystal. Which is more or less to say that what is interesting is not the photo finish of a 100 meter race but how a sprinter's body behaves (in terms of movement) along a certain distance of the race.
    5) 1-4 I wrote above may be nonsense since I haven't read the article in nature yet
    6) There are dozens of proteins and mechanisms that allow bacteria to be resistant. See MDR proteins - multidrug resistance

  2. It should be noted that bacteria have several methods of resistance to drugs, including the transfer of sequences of genetic material between bacteria (a kind of "sexual reproduction") that give them resistance.

    There is no doubt that this is a breakthrough, in understanding one of the defense mechanisms and developing future drugs.

    Hanan Sabat
    http://WWW.EURA.ORG.IL

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