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- Without a single strain: new antibiotic will kill invincible Staphylococcus aureus
Without a single strain: new antibiotic will kill invincible Staphylococcus aureus
Russian scientists have synthesized a new antibiotic capable of destroying one of the most drug-resistant strains of Staphylococcus aureus. This bacterium has developed resistance to most classic antibacterial agents, so the fight against it has become a serious problem. The preclinical stage of creating a drug based on a new compound will take about a year. According to experts, doctors need a new drug, but further research is needed to confirm its effectiveness and safety for humans.
A new substance for fighting staphylococcus
MIPT specialists have synthesized a new antibiotic against drug-resistant Staphylococcus aureus. This dangerous bacterium often causes serious illnesses. Many of its strains have developed resistance to classical antimicrobials, so the fight against them has become a serious problem. Experiments have shown that the molecule proposed by scientists effectively destroys the infection and can become the basis for a new drug.
— We have studied a group of triazenoindole substances and selected the most effective molecule from them. These compounds are used as prototypes of drugs against tuberculosis, its causative agent is mycobacteria, therefore it is a natural candidate for use as an antibiotic against staphylococcus. They are also known to have an antifungal effect. Experiments have confirmed this. We assume that the molecule has a double effect on the bacterium. The synthesis of cell membrane components is disrupted, as well as the work of the DNA gyrase enzyme, but we intend to study this mechanism in more detail in future studies," Denis Kuzmin, one of the authors of the work, director of the Phystech School of Biological and Medical Physics at MIPT, told Izvestia.
According to the scientist, the preclinical stage of the study, including animal testing, will take about a year. Then the developers plan to move on to experiments involving humans.
Staphylococcus aureus (Staphylococcus aureus) is a bacterium that can cause skin infections, pneumonia, bloodstream infections, and other serious conditions. One of the most antibiotic—resistant strains is methicillin-resistant staphylococcus (MRSA), which scientists are trying to find a cure for.
Currently, vancomycin, linezolid, clindamycin, daptomycin, ceftaroline and trimethoprim sulfamethoxazole are recommended for the treatment of MRSA infection. However, these drugs are increasingly losing their clinical effectiveness due to emerging bacterial resistance. According to the authors of the study, the hybrid mechanism of action of the proposed substance suggests that it will be able to overcome bacterial resistance.
— The study was conducted for two years. In this article, we describe the synthesis of an original library of 20 triazenoindoles with high activity against a wide range of clinical isolates of methicillin-resistant staphylococcus aureus with multiple drug resistance. The leading compound BX-SI043 showed high activity against 41 clinical isolates of MRSA," said Denis Kuzmin.
The drug candidate BX-SI043 has demonstrated good results in toxicological tests on both cells and animals. In addition to its strong antibacterial activity, it showed a high selectivity index, which means that the antibiotic acts specifically on bacteria and is low toxic to animal and human cells. Staphylococcus aureus most often causes skin infections. The ability to suppress it in combination with antifungal activity opens up prospects for BX-SI043 as a drug against this type of disease.
A deadly infection
MRSA is one of the most well-known antibiotic-resistant strains of bacteria. This is an evolved common Staphylococcus aureus, which can cause various soft tissue infections, skin and wound infections, pneumonia, and up to sepsis. And since it is resistant to the most commonly used antibiotics, beta—lactams, its treatment is very difficult and it can cause death, Mikhail Bolkov, a researcher at the Institute for the Study of Aging at the Russian State Scientific and Clinical Center of the Pirogov Russian National Research Medical University of the Russian Ministry of Health, explained to Izvestia.
"Even before COVID-19, there was a prediction that antibiotic-resistant strains were one of the biggest threats, and solving this problem is extremely expensive because bacteria evolve and adapt to drugs faster than we produce them," he said.
The creation of a domestic antibiotic that can defeat MRSA is a big step forward. Triazenoindoles will work by several mechanisms at once, which will make it more likely that they will overcome drug resistance.
— Such developments are extremely important in modern medical microbiology both from the point of view of its practical aspects and from the point of view of the fundamental direction. The search for new groups of antibacterial drugs is a priority task not only in Russia, but also in the world. The groups of substances with potential antimicrobial effects obtained by colleagues open up new opportunities in the fight against infectious pathology caused by polyresistant staphylococcus aureus," said Artem Lyamin, Director of the Scientific and Educational Professional Center for Genetic and Laboratory Technologies at the SamSMU of the Russian Ministry of Health.
Given the haphazard use of antibacterial drugs, microorganisms have an order of magnitude more opportunities to develop antibiotic resistance than humanity has to develop a new drug, added Sergey Voznesensky, associate professor of the Department of Infectious Diseases with courses in Epidemiology and Phthisiology at RUDN University.
— Therefore, the drug candidate BX-SI043, developed by a consortium of Russian specialists, has a huge application potential and will be in demand by practical healthcare professionals. However, it is worth considering the fact that from the stage of a promising drug model to its introduction into clinical practice, there are several stages of clinical trials that will reliably confirm its effectiveness against staphylococcal infection and safety for humans," the expert said.
According to the developers, sooner or later the bacteria will develop resistance to the new drug, but until then it will be beneficial.
In addition to the MIPT staff, their colleagues from the Kurchatov Center for Genomic Research, the I.M. Sechenov First Moscow State Medical University of the Russian Ministry of Health, the Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences and the A.N. Severtsov Institute of Ecology and Evolution of the Russian Academy of Sciences participated in the development of the antibiotic.
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