Researchers at the Karolinska Institute, Umeå University and the University of Bonn have identified a new group of molecules with antibacterial effects against a variety of antibiotic-resistant bacteria. As the properties of molecules can easily be chemically altered, they wish to develop new antibiotics that are effective with few side effects.
THE PHENOMENON OF ANTIBIOTICS RESISTANCE
Antibiotic resistance is the ability of microorganisms such as bacteria, viruses, fungi or parasites to grow in the presence of a drug that would normally kill or limit their growth. As a result, conventional treatments become ineffective. Infections thus become more serious, leading to longer illness, higher treatment costs, and a higher risk of death.
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Antibiotic resistance is a public health threat worldwide, affecting the health and lives of people and the overall, sustainable development of an entire country. Vietnam is one of the countries that, in recent years, has witnessed the growing threat of antibiotic resistance, due to the inappropriate use of antibiotics at all levels of the healthcare system. , in aquaculture, in livestock and in the community.
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MECHANISM OF ANTIBIOTIC RESISTANCE OF BACTERIA
First: bacteria prevent antibiotics from penetrating inside them by strengthening or altering the structure of their protective membranes. For example, Gram-negative bacteria have an outer membrane to prevent antibiotics from penetrating inside.
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Second: bacteria create efflux pumps to pump antibiotics out. For example, blue pus bacillus can create efflux pumps for quinolone and beta lactam antibiotics, leading to the antibiotic being inactivated.
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Third: bacteria produce enzymes to destroy antibiotics such as penicillinase, extended-spectrum beta lactamase, carbapenemase... This is a common way that bacteria create to fight most groups. antibiotic. For example, Klebsiella pneumoniae produces the carbapenemase enzyme KPC, which destroys the carbapenem group; Escherichia coli produces extended-spectrum beta lactamase ESBL resistant to cephalosporin...
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Fourth: bacteria change the structure of their parts, making antibiotics unable to recognize their target. For example, changing the penicillin-binding protein PBP is how bacteria resist beta lactam antibiotics. Mutating the gene encoding the DNA-gyrase enzyme is a way to resist quinolone antibiotics.
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MECHANISM OF ACTION OF ANTIBIOTICS
Each type of antibiotic will have its own mechanism of action. The mechanisms of action of antibiotics all aim at the common task of attacking and destroying bacterial cells to protect the body.
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Attacks bacterial protective structures:
+ Antibiotics will inhibit the synthesis of the peptidoglycan skeleton (bacterial protective shell), causing bacteria to be born without a protective shell and therefore easily destroyed.
E.g.: beta-lactamase group, vancomycin
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Blocking protein production in bacteria:
+ Antibiotics act on bacterial 70S ribosomes.
+ Binds to the 30S subunit to prevent the activity of transfer RNA (streptomycin) or inhibit the function of transfer RNA (tetracycline).
+ Binds to the 50S subunit to hinder the binding and creation of amino acids that create cell life (erythromycin, chloramphenicol).
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Inhibition of nucleic acid synthesis:
+ Affects and prevents DNA replication. For example, quinolone antibiotics inhibit the production of the gyrase enzyme, making the molecule unable to open the helix.
+ Hinders RNA biosynthesis (rifampicin).
+ Inhibits biosynthesis necessary for cells to prevent the growth of bacterial cells (sulfamide, trimethoprim).
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THCz – tetrahydrocarbazole:
Researchers at Karolinska Institutet and Umeå University in Sweden tested a large number of chemical compounds for their ability to suppress pneumococcus, the most common type of bacteria that causes community-acquired pneumonia. Initial tests were carried out in collaboration with the Swedish Chemical-Biological Society (CBCS), a national research facility at SciLifeLab. Following this screening, the researchers, collaborating with the University of Bonn in Germany, discovered that a group of molecules called THCz – tetrahydrocarbazole inhibits bacterial cell wall formation by by targeting lipid II and other undecaprenyl pyrophosphate-containing lipid precursors. These molecules can also prevent the formation of the “sugar capsule” that pneumococcus needs to escape the immune system and cause disease.
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Birgitta Henriques Normark said: "Lipid II is a very attractive target for new antibiotics. We have identified the first small antibacterial compounds that act by binding to this lipid molecule and in In our research, we found no drug-resistant mutant bacteria, which is very promising." Professor at the Department of Microbiology, Oncology and Cell Biology, Karolinska Institutet, and one of three corresponding authors of the paper.
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Lipid II is a pentapeptide peptidoglycan disaccharide subunit linked to an undecaprenyl lipid via a pyrophosphate group. It is synthesized in the cytoplasm and transported to the outside of the plasma membrane to form the cell. Therefore, it is a relatively accessible target for antibiotics.
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Currently, lipid II-binding antibiotics of at least five chemical groups are known, including glycopeptides (vancomycin) antibiotics (nisin), defensins - a family of antibacterial peptides (plectasin), lipopeptides (empedopeptin) and depsipeptide (teixobactin). What these agents have in common is that they bind to the molecule's lipid sequestrant II and make it unavailable for peptidoglycan biosynthesis.
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More recently, the new antibiotic daptomycin has been shown to target undecaprenyl-containing lipid mediators.
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In experiments, THCz has been shown to have antibacterial effects against many antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA); vancomycin-resistant enterococci (VRE) and penicillin-resistant pneumococci (PNSP). Antibacterial effects were also found against gonococci - which cause gonorrhea - and mycobacteria - bacteria that can cause serious diseases such as tuberculosis in humans. The researchers were unable to identify any bacteria that developed resistance to THCz in a laboratory setting.
“We will now also begin efforts to modify the THCz molecule, allowing it to penetrate the outer cell member,” said Tanja Schneider, professor at the Institute of Pharmaceutical Microbiology at the University of Bonn. found in some bacteria, especially difficult-to-treat multidrug-resistant bacteria,” one of the corresponding authors.
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MEANINGS
Đến sự xuất hiện đáng báo động của tình trạng kháng thuốc với hầu hết các loại kháng sinh và nhu cầu sử dụng các loại kháng sinh mới, thì việc phát hiện một loại phân tử nhỏ - THCz, có thể hiện hoạt tính diệt khuẩn chống lại vi khuẩn gram dương và lọc gram âm, có tầm quan trọng rất lớn. THCz mồi tiêu đến tổng hợp vỏ tế bào và có thể dễ dàng được tổng hợp và sửa đổi nên lại hứa hẹn cho sự phát triển của các chất ức chế thành tế bào vi khuẩn.
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Summary and editing: Hai Anh – Phacogen Institute of Technology;
(Biotechnology Engineer - Hanoi University of Science and Technology)
Referral:
https://www.pnas.org/content/118/47/e2108244118
https://www.who.int/vietnam/vi/health-topics/antimicrobial-resistance
https://www.vinmec.com/vi/thong-tin-duoc/su-dung-thuoc-toan/nao-la-khang-khang-sinh/
https://medlatec.vn/tin-tuc/tim-hieu-ve-co-che-tac-dung-cua-khang-sinh-s195-n21480
https://www.sciencedaily.com/releases/2021/11/211117100136.htm
