N 2 (183) 2023. P. 15–20

DYNAMICS OF THE FORMATION OF RESISTANCE TO BENZYLPENICILLIN IN STAPHYLOCOCCUS AUREUS STRAINS ISOLATED IN DIFFERENT HISTORICAL PERIODS

О. G. Peretyatko, Yu. А. Yagnyuk, N. I. Sklyar, S. L. Krestetska,
G. M. Bolshakova, Т. V. Kholodna

State Institution “Mechnikov Institute of Microbiology and Immunology National Academy of Medical Sciences of Ukraine”, Kharkiv, Ukraine

DOI 10.32782/2226-2008-2023-2-2

Introduction. To establish antibiotic resistance evolution regularities, it is necessary to study the peculiarities of its formation. One of the ways to reproduce the natural evolution of antibiotic resistance is to model it in in vitro studies.

The aim of the research – to study the speed of resistance formation to benzylpenicillin in S. aureus strains of different isolation periods in in vitro experiments.

Research materials and methods. The subjects of the study included 12 S. aureus strains sensitive to beta-lactam antibiotics, isolated in different historical periods: 4 – in the pre-antibiotic period (from 1930 to 1943), 4 – in the meta-antibiotic period (from 1962 to 1969), 4 – in the modern period (2020). Adaptation of staphylococci to benzylpenicillin was carried out by passage on Mueller-Hinton agar with increasing concentrations of benzylpenicillin, starting with subbactericidal, a total of 30 passages were carried out. Statistical processing of the obtained data was conducted using methods of non-parametric statistics by means of the licensed statistical software package “Statistica 6.1” (serial number – AGAR909E415822FA).

Research results and discussion. It was established that after the cycle of resistance adaptive selection, the Minimum Bactericidal Concentration (MBC) of benzylpenicillin for all strains of the pre-antibiotic period was 2.0 μg/ml and exceeded the initial values by 125–250 times. In strains of staphylococci isolated during the meta-antibiotic period, the average value of the minimum bactericidal concentration of the antibiotic was 3.63 μg/ml, the multiplicity of increase – from 31.3 to 250 times. The MBC of benzylpenicillin for modern strains has increased 125–500 times relative to the initial values, with an average value of 16 μg/ml.

Conclusions. As a result of benzylpenicillin resistance adaptive selection, subpopulations of S. aureus strains were obtained, able to grow in the presence of the antibiotic with MBC that exceeded the initial values in the range from 31.3 to 500 times. It was established that S. aureus strains isolated in the modern period were characterized by faster rates of adaptation and adapted to higher concentrations of benzylpenicillin than staphylococci isolated in the pre- and meta-antibiotic periods.

Key words: S. aureus strains isolated in different historical periods, benzylpenicillin, resistance modeling.

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