Can antibiotics made by bacteria kill itself?

The copper of Pseudomonas aeruginosa (picture source: Aniplex) in "Working Cell" is a reliable sterilization tool for humans
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Replacing some surfaces that are touched daily with copper can help prevent the spread of some bacteria
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However, if certain harmful bacteria are not afraid of copper, how can humans deal with them? Scientists have also been studying this issue.
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Author | Chestnut Editor | Clefable copper is an important trace element in the human body
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One of its jobs is to act as a part of the immune system to poison invading microorganisms
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Even if they don't understand the truth behind this, the ancients thousands of years ago knew that copper was used for disinfection and sterilization
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For example, the Phoenicians after the battle applied debris from the bronze sword to their wounds to prevent infection and accelerate healing
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Ancient Chinese medical classics also contain records of the treatment of diseases with copper coins
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But there is a kind of "super bacteria" that is not only difficult to kill by copper, but also uses copper calmly to produce an antibiotic
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It is called Pseudomonas aeruginosa (Pseudomonas aeruginosa)
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Scientists have always wanted to defeat this kind of pathogenic bacteria that can infect the human body.
In the spirit of knowing yourself and the enemy, they first figured out how it makes antibiotics this time and published the results in the journal Science
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Wait, aren't antibiotics used to kill bacteria? What are bacteria doing to make antibiotics? Not being killed by copper, but dominated by copper.
First, briefly explain why copper can kill bacteria.

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Copper ions are unstable and easily participate in redox reactions, changing between monovalent copper and divalent copper
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When monovalent copper becomes divalent copper, the generated hydroxyl radical (-OH) is a kind of reactive oxygen species, which will cause oxidative damage to various macromolecules in the cell
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This is why bacteria are afraid of copper
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It is precisely because of this that all microorganisms have evolved a copper processing mechanism, whether it is transported away or isolated, the ultimate goal is to keep the cytoplasm of free copper free
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But even with this mechanism, if the copper concentration in the environment is too high, most bacteria will still be difficult to survive
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The protagonist of this article, Pseudomonas aeruginosa, is not so afraid of copper
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This bacterium is also called "Pseudomonas aeruginosa" because it gets its name from the discharge of pus aeruginosa when it infects the wound
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Pseudomonas aeruginosa is very common and is not difficult to find in water, soil, or on human skin
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A research team led by scientists at the University of North Carolina at Chapel Hill believes that Pseudomonas aeruginosa has special skills in dealing with elevated copper concentrations
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Because they can synthesize a broad-spectrum antibiotic called Fluopsin C: part of the copper is used in the production of this antibiotic
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 Fluopsin C antibiotic (picture source: original paper) The way Pseudomonas aeruginosa dominates copper is to use two identical groups to firmly grasp a copper ion, like a crab holding its prey with tongs
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The crab claws and can be called "sequestration", so this reaction is also known as "chelation", the resulting product is an antibiotic C Fluopsin
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When copper is locked in the antibiotic molecule and becomes a part of the molecule, it is difficult to harm bacteria like free copper ions
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Scientists have determined the synthetic pathway of this antibiotic molecule through a series of experiments
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The most important part is probably the manufacturing process of the "pliers": at first it was just an ordinary amino acid-cysteine, relying on the efforts of five enzymes, it finally became N-methylthiohydroxamic acid group.
Regiment
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And two such groups can clamp the copper
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Crab claws (photo source: David Clode/Unsplash) Among the five enzymes involved in the manufacture of tongs, there are two lyases, two iron-dependent enzymes, and one methyltransferase
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Previous studies have found that these enzymes in Pseudomonas aeruginosa are all encoded by the same operon (PA3515–PA3519) in the genome
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Moreover, when the copper concentration in the environment increases, the enzyme expressed by this operon will be much larger than usual
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The above research on the operon used the PAO1 strain of Pseudomonas aeruginosa; this time the team also used the same strain to confirm that when the gene in the operon was modified, the scientists could not detect the Pseudomonas aeruginosa.
Antibiotic Fluopsin C too
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Therefore, scientists believe that when bacteria encounter a high concentration of copper, the operation of holding the copper with their homemade pliers and reducing the copper concentration is a kind of stress response and protects the bacteria from the poison of heavy metals
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Although it is to protect yourself, will the antibiotics produced by bacteria really kill you? It's hard to kill yourself, but easy to kill other bacteria.
As early as the 1970s, scientists had extracted Fluopsin C, an antibiotic, and began to understand its efficacy
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As mentioned above, it is a broad-spectrum antibiotic that has a lethal effect on a wide variety of bacteria.
It eats both gram-positive and gram-negative bacteria, and it is also effective against fungi such as yeast
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Some powerful bacteria, such as Acinetobacter baumanii (Acinetobacter baumanii) and Staphylococcus aureus (Staphylococcus aureus), have multi-drug resistance and can resist many antibiotics, but they will be inhibited by Fluopsin C antibiotics.
It is inhibited even when the antibiotic concentration is very low (a few micrograms per milliliter)
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Therefore, many scientists are also studying the use of this antibiotic to treat infections caused by multi-drug resistant bacteria
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But it is such a broadly bactericidal antibiotic, but it is much weaker in the face of Pseudomonas aeruginosa
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Among them, the PAO1 strain can withstand more than 70 micrograms/ml of Fluopsin C antibiotics
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Pseudomonas aeruginosa is much more resistant to this drug than other bacteria that participated in the test
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The upper part is the antibiotic Fluopsin C synthesized by bacteria, and the lower part is the synthetic drug copper pyrithione.
Both have similar structures (picture source: original paper).
After that, scientists used a synthetic drug to test the bacteria.
The reaction of this drug is called copper pyrithione, and the structure of Fluopsin C is somewhat similar
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It was found that the PAO1 strain of Pseudomonas aeruginosa was still more tenacious than the other strains in the test, and the concentration of 40 μg/ml was not enough to pose a threat to it
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In other words, the homemade antibiotic Fluopsin C of Pseudomonas aeruginosa can easily kill many other bacteria without much harm to themselves and their companions, which may become a competitive advantage for them in nature
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Among Pseudomonas aeruginosa, is there only one strain called PAO1 that can produce antibiotics? Do other strains have the same skills? If you remember, there are five enzymes involved in the synthesis of Fluopsin C antibiotics, and scientists have discovered that the genes encoding these enzymes are present in 99.
6% of Pseudomonas aeruginosa strains
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In other words, among the 4955 Pseudomonas aeruginosa strains, 4537 strains may all retain the ability to make Fluopsin C antibiotics
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This ability not only helps bacteria resist the attack of copper ions, but also helps them attack other microorganisms
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Is this bacteria invincible? After reading this, you probably also feel that Pseudomonas aeruginosa is by no means idle
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The human body's immune system uses copper to block the invasion of microorganisms, so when a bacterium has the setting of "not afraid of copper", its virulence cannot be underestimated
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In the human body, Pseudomonas aeruginosa can infect almost any part of the body, such as the blood, lungs, urinary tract, etc.
It may be life-threatening in severe cases
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For hospitalized patients, the risk of infection is higher than for healthy people, especially those who have wounds, followed by catheters, or use ventilators
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This kind of bacteria is very common.
As long as someone has been in contact with water or soil contaminated by Pseudomonas aeruginosa, they have the opportunity to spread the bacteria by touching medical equipment or other surfaces
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Pseudomonas aeruginosa, also called Pseudomonas aeruginosa (picture source: CDC) And when a person is infected with Pseudomonas aeruginosa, medical workers usually send samples of the patient to the laboratory to test which antibiotics are effective against the infected strain , And then provide a treatment plan
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However, as the drug resistance of Pseudomonas aeruginosa increases, the treatment of infected persons has become more and more difficult.
In the face of some multi-drug resistant strains, treatment options may be very limited
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So, many scientists are also exploring other treatments
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For example, in 2011, the research team of Nanyang Technological University edited the DNA of Escherichia coli and designed it as a "biological bomb": Escherichia coli can recognize special molecules released by Pseudomonas aeruginosa when they communicate with each other.
Once this chemical signal is detected, it will Two genes can be activated, one is responsible for producing a kind of pyocyanin (pyocin S5) that is harmful to Pseudomonas aeruginosa, and the other is responsible for rupturing the E.
coli, releasing pyocyanin, and attacking Pseudomonas aeruginosa
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Experiments have proved that this method can kill 99% of Pseudomonas aeruginosa
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However, before we use similar therapies, frequent hand washing is the primary strategy to deal with "super bacteria"
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Original paper: https:// Reference link: https:// .
ncbi.
nlm.
nih.
gov/pmc/articles/PMC4464932/https://pubmed.
ncbi.
nlm.
nih.
gov/28760827/https:// /11/23_11_546/_article/-char/ja/https:// / "Global Science" December new issue of pre-sale is in the picture or read the original text.
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