The Troika of Trojans
Scientists investigated new antimicrobial compounds
Natalia Safronova, "Scientific Russia"
Skoltech researchers have studied new antimicrobial compounds acting on the "Trojan horse" principle: they, under the guise of a harmless compound, penetrate into the bacterial cell and destroy it, blocking the synthesis of proteins. Scientists have managed to identify new gene clusters similar to those of the well-known "Trojan horses" and encoding enzymes for the biosynthesis of new antimicrobial compounds that require further study. A review article on the results of the study was published in the journal RSC Chemical Biology (Travin et al., Natural Trojan horse inhibitors of aminoacyl-tRNA synthetases).
In the fight against microbes, the most difficult task is to crack a powerful external defense and, having penetrated into the right cell, use a "deadly" weapon. Some antimicrobial compounds act according to the well-known "Trojan horse" principle: posing as a "friendly" compound, they penetrate into the cell and, once inside, release their "Achaeans", which can, for example, block aminoacyl-tRNA synthetases – key enzymes that ensure the correctness of the translation of genetic information.
Skoltech graduate student Dmitry Travin, Professor Konstantin Severinov and the head of the biomedical laboratory Svetlana Dubiley investigated three well-known categories of inhibitors acting on the principle of "Trojan horse": albomycin, microcin C-like compounds and agrocin 84.
These three types of "biological weapons" mimic an iron−containing compound - siderophore, some peptides and opin (the energy source of the bacterium), respectively.
According to the authors, bacteria have only one way to protect themselves from antimicrobial drugs of this type: to neutralize transport proteins that deliver a seemingly harmless compound inside the cell. Despite the fact that bacteria can include such protection quite often, "Trojan horses"-inhibitors can be used to create medicines, since pathogenic bacteria partially neutralized in this way also become less dangerous for the host organism.
The researchers conducted a bioinformatic search and found other clusters of genes similar to those that encode known antimicrobial drugs that act on the principle of a "Trojan horse". "We conducted a brief bioinformatic analysis, the results of which showed that the entire diversity of the three classes of molecules we considered has not yet been fully studied. If the properties of these compounds are confirmed experimentally, it will be possible to talk about creating new effective antibiotics based on them," the article notes.
The study was conducted with the participation of specialists from the Institute of Gene Biology of the Russian Academy of Sciences and the Waxman Institute of Microbiology at Rutgers University (USA).
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