Searching for mechanisms of action of antimicrobials

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Searching for mechanisms of action of antimicrobials Ana Bárbara Polo1 · Rodrigo Luiz Fabri2 · Ana Carolina Morais Apolônio1  Received: 10 March 2020 / Revised: 5 June 2020 / Accepted: 15 June 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract Although development of antimicrobial resistance by bacteria is a natural phenomenon, the antibiotic resistance crisis is a reality that leads us in a gap of antimicrobial alternatives on therapeutics. Considering this cruel reality and committed to contribute to look for new antibacterial agents, this manuscript presents a review of easy laboratory methods that evaluate the mode of action of compounds, since it is a basic requirement for the discovery and development of new drugs. The literature was screened by searching the keywords “mode of action”, “antibiotic”, “antimicrobial activity”, “inhibition mode”, “method” and “bacteria” in Pubmed, Scopus, Science Direct and BVS in a period of time from 2000 to 2019. This review demonstrates the wide variety of methods that can be employed in research on mechanisms of action of antibacterial substances. Therefore, we compiled different protocols (presented in the supplementary material), available in the literature, with the purpose of facilitating the start of experiments. Keywords  Drug screening · Antibiotic resistance · Drug development · Mode of action

Introduction Even though the problem of bacterial resistance to antibiotics is widely known nowadays, it has not always been this way. During the pre-antibiotic era, human life expectancy was very low and most of the deaths were due to infectious diseases (Jayachandran 2018). Nevertheless, science evolved, and antibiotics were discovered, quickly transforming medicine and saving many lives. However, the microorganisms present high genetic versatility and adaptability. Thus, the landmark of the era of antibiotics was the discovery of penicillin in 1928 by Alexander Fleming (Sengupta Communicated by Dr. Djamel DRIDER. Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s0020​3-020-01959​-z) contains supplementary material, which is available to authorized users. * Ana Carolina Morais Apolônio [email protected] 1



Laboratory of Bacterial Physiology and Molecular Genetics, Department of Parasitology, Microbiology and Immunology, Institute of Biological Sciences, Federal University of Juiz de Fora, Juiz de Fora, MG 36036‑900, Brazil



Bioactive Natural Products Laboratory, Department of Biochemistry, Institute of Biological Sciences, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil

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et al. 2013); its prescription started in the 1940s (Michiels et al. 2016) and in 1947 penicillin resistance was found in Staphylococcus aureus bacteria (CDC 2013). Sadly, the bacteria became quite resistant to the new antibiotic in short period of time (CDC 2013). Even though development of antimicrobial resistance by bacteria is a natural phenomenon, the antibiotic resistance crisis is accel