Molecular mechanisms of antimicrobial defense strategy of bacterial cell

Abstract

INTRODUCTION: Solution to the problem of antibiotic resistance (ABR) and the continuing spread of multidrug resistant strains is a strategic task of practical healthcare. An important tool for improving antimicrobial pharmacotherapy, along with active search for new effective drug compounds, can be a detailed investigation of the prime cause of the emergence and effect of the extracellular environment on the molecular mechanisms of bacterial resistance to chemotherapeutic drugs.

AIM: Analysis of the literature devoted to the molecular mechanisms of antimicrobial defense strategy of the bacterial cell against the effect of medical drugs, and to promising strategies of combating antibiotic-resistant agents.

MATERIALS AND METHODS: A search and analysis of the scientific literature was conducted in PubMed, eLibrary, Europe PMC, WoS, CyberLeninka and other databases for the last 5 years. The search queries included the following word combinations: for Russian-language publications the problem of ABR, environmental factors of antibiotic sensitivity, resistance mechanisms, resistance genes, mobile genetic elements; for English-language publications: antibiotic resistance evolution, antibiotic resistance genes, antibiotic resistance in biofilms, transmission of antibiotic resistance. A total of 100 literature sources published from 2018 to 2022 have been analyzed, of which 44 were included in the review.

An analysis of domestic and foreign sources showed that a significant role in the development of ABR in microorganisms is assigned to enzymatic beta-lactamase activity, specific protective proteins of microorganisms, as well as the ability of pathogenic strains to form biofilms. Besides, according to the results of studies, the main source of resistance genes is the environment, where the transfer of ABR genes between representatives of different bacterial taxa occurs. Promising areas in the fight against antibiotic-resistant pathogens are mathematical modeling, synthetic biology, phage therapy.

CONCLUSION: In modern studies, the tendency of microorganisms to ABR presents a serious evolutionary and ecological problem. The uncontrolled and unjustified current use of antibacterial drugs in medicine, veterinary medicine and agriculture provoked the activation of the mechanisms of bacterial cell defense known by the moment, and caused enhancement of the adaptive capacity of bacterial pathogens and spread of multidrug resistant strains. The review also provides data on various strategies aimed at solving the ABR problem.

Keywords

antibacterial agents / drug resistance / beta-lactamases / phage therapy / biofilms / antibiotic-resistant strains / efflux pumps / MfpA target molecule / transposable genetic elements / ribosomal proteins

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