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    Home > Biochemistry News > Biotechnology News > How to solve the problem of antibiotic abuse?

    How to solve the problem of antibiotic abuse?

    • Last Update: 2021-06-28
    • Source: Internet
    • Author: User
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    Antibiotics can be said to be the standing medicine of every family.
    Since the birth of antibiotics, it has helped humans treat meningitis, tuberculosis and other bacterial infections, saving countless lives

    However, the abuse of antibiotics can also cause many adverse effects on the human body, the biggest of which is to promote bacterial resistance to antibiotics


    At present, the abuse of antibiotics has become one of the problems that threaten global public health.
    China is the world's largest producer of antibiotics and half of the world's consumption, and its unreasonable use of antibiotics has exceeded 50%

    The World Health Organization has reported that 700,000 people die from antibiotic resistance every year

    2050, antibiotic resistance will cause 10 million deaths every year .
    Strictly resisting the abuse of antibiotics has become one of the ways to reduce antibiotic resistance.
    However, in addition to reducing the frequency of antibiotic use, how should the problem of super bacteria's resistance to antibiotics be fundamentally solved?

    Recently, a research team from New York University in the United States published a research report titled Inhibitors of bacterial H2S biogenesis targeting antibiotic resistance and tolerance in Science.
    The article explores how to enhance the bactericidal effect of existing antibiotics by attacking the defense mechanism of pathogens-H2S biogenesis system And proved the effective auxiliary effect of bCSE inhibitors on bactericidal antibiotics


    DOI: 10.

    Studies have pointed out that at present, one way to solve the problem of antibiotic resistance is to break the defense system that protects pathogens from the interference of antibiotics.
    This defense system releases hydrogen sulfide (H2S) to encourage bacteria to resist oxidative stress, thereby producing resistance to antibiotics.

    Therefore, the researchers started from this, selecting the two most common human pathogens-Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa, and using computer simulation and in vivo detection methods to screen and verify that they can target H2S Small molecule compounds


    Since almost all pathogens produce H2S through homologous enzymes such as mammalian cystatin lyase (CSE) and cystatin b synthetase (CBS), the researchers first verified which enzyme is the main source of H2S
    Tests have proved that CSE is the main site for the production of H2S by Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa.
    When bCSE (bacterial CSE) is absent, it will result in the loss of H2S products of the two pathogens.
    Therefore, CSE’s Inactivation will stimulate the sensitivity of the two bacteria to bactericidal antibiotics, which will be killed by antibiotics


    As a result, the researchers used bCSE as the target, after structure-based computer virtual screening, selected 3.
    2 million commercially available small molecule compounds, and continued to screen 40 sites that can inhibit bCSE

    After verifying the effectiveness of bCSE inhibitors in vivo and in vitro, the researchers finally screened out the three most effective small molecule compounds and named them NL1, NL2, and NL3


    The researchers used the Staphylococcus aureus sepsis model and the Gram-negative Pseudomonas aeruginosa lung infection model to further verify the three compounds in vivo and in vitro.
    The results showed that NL1, NL2, and NL3 are comparable to antibiotics.
    The synergistic effect proves that bCSE inhibitors can enhance the effectiveness of antibiotic therapy in the body.
    Among them, NL1 is non-toxic and safe for different types of human cells in different tests

    At the same time, when NL1 is used in combination with the antibiotic Gentamycin sulfate (Gentamycin, Gm), it can significantly reduce the bacterial load in the lungs

    All these prove that bCSE inhibitors can inhibit the production of H2S, thereby promoting the bactericidal efficacy of antibiotics


    The chemical structure and experimental results of the selected bCSE inhibitors

    So far, no targeted drug for retaining bacteria has been approved by the U.

    The researchers said that the study provides a new direction for exploring the combination therapy of bCSE inhibitors and approved or new antibiotics.
    By using the ability of bCSE inhibitors to interfere with the tolerance of bacteria, the antibiotic-bCSE inhibitor combination will be able to reduce acute Failure to treat infections can also shorten the course of treatment, and the likelihood of developing or spreading antibiotic resistance will also be reduced


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