Chapter 4 : Mechanisms of Bacterial Resistance to Antimicrobial Agents

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With regard to their structures and functions, antimicrobial agents represent a highly diverse group of low-molecular-weight substances which interfere with bacterial growth, resulting in either a timely limited growth inhibition (bacteriostatic effect) or the killing of the bacteria (bactericidal effect). For more than 60 years, antimicrobial agents have been used to control bacterial infections in humans, animals, and plants. Nowadays, antimicrobial agents are among the most frequently used therapeutics in human and veterinary medicine ( ). In the early days of antimicrobial chemotherapy, antimicrobial resistance was not considered as an important problem, since the numbers of resistant strains were low and a large number of new highly effective antimicrobial agents of different classes were detected. These early antimicrobial agents represented products of the metabolic pathways of soil bacteria (e.g., , ) or fungi (e.g., , , ) ( Table 1 ) and provided their producers with a selective advantage in the fight for resources and the colonization of ecological niches ( ). This in turn forced the susceptible bacteria living in close contact with the antimicrobial producers to develop and/or refine mechanisms to circumvent the inhibitory effects of antimicrobial agents. As a consequence, the origins of bacterial resistance to antimicrobial agents can be assumed to be in a time long before the clinical use of these substances. With the elucidation of the chemical structure of the antimicrobial agents, which commonly followed soon after their detection, it was possible not only to produce antimicrobial agents synthetically in larger amounts at lower costs, but also to introduce modifications that altered the pharmacological properties of these substances and occasionally also extended their spectrum of activity.

Citation: van Duijkeren E, Schink A, Roberts M, Wang Y, Schwarz S. 2018. Mechanisms of Bacterial Resistance to Antimicrobial Agents, p 51-82. In Schwarz S, Cavaco L, Shen J (ed), Antimicrobial Resistance in Bacteria from Livestock and Companion Animals. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.ARBA-0019-2017
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