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      The ecology of plasmid-coded antibiotic resistance: a basic framework for experimental research and modeling

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          Highlights

          • Understanding plasmid-coded antibiotic resistance from an ecological perspective.

          • Plasmid fitness considering complex biotic interactions and evolutionary modifications.

          • Comparison of biofilm versus plankton and artificial versus natural environments.

          • Introduction and brief review of population-level and individual-based models.

          Abstract

          Many antibiotic resistance genes are associated with plasmids. The ecological success of these mobile genetic elements within microbial communities depends on varying mechanisms to secure their own propagation, not only on environmental selection. Among the most important are the cost of plasmids and their ability to be transferred to new hosts through mechanisms such as conjugation. These are regulated by dynamic control systems of the conjugation machinery and genetic adaptations that plasmid-host pairs can acquire in coevolution. However, in complex communities, these processes and mechanisms are subject to a variety of interactions with other bacterial species and other plasmid types. This article summarizes basic plasmid properties and ecological principles particularly important for understanding the persistence of plasmid-coded antibiotic resistance in aquatic environments. Through selected examples, it further introduces to the features of different types of simulation models such as systems of ordinary differential equations and individual-based models, which are considered to be important tools to understand these complex systems. This ecological perspective aims to improve the way we study and understand the dynamics, diversity and persistence of plasmids and associated antibiotic resistance genes.

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          Most cited references119

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          Molecular mechanisms of antibiotic resistance.

          Antibiotic-resistant bacteria that are difficult or impossible to treat are becoming increasingly common and are causing a global health crisis. Antibiotic resistance is encoded by several genes, many of which can transfer between bacteria. New resistance mechanisms are constantly being described, and new genes and vectors of transmission are identified on a regular basis. This article reviews recent advances in our understanding of the mechanisms by which bacteria are either intrinsically resistant or acquire resistance to antibiotics, including the prevention of access to drug targets, changes in the structure and protection of antibiotic targets and the direct modification or inactivation of antibiotics.
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            CRISPR interference limits horizontal gene transfer in staphylococci by targeting DNA.

            Horizontal gene transfer (HGT) in bacteria and archaea occurs through phage transduction, transformation, or conjugation, and the latter is particularly important for the spread of antibiotic resistance. Clustered, regularly interspaced, short palindromic repeat (CRISPR) loci confer sequence-directed immunity against phages. A clinical isolate of Staphylococcus epidermidis harbors a CRISPR spacer that matches the nickase gene present in nearly all staphylococcal conjugative plasmids. Here we show that CRISPR interference prevents conjugation and plasmid transformation in S. epidermidis. Insertion of a self-splicing intron into nickase blocks interference despite the reconstitution of the target sequence in the spliced mRNA, which indicates that the interference machinery targets DNA directly. We conclude that CRISPR loci counteract multiple routes of HGT and can limit the spread of antibiotic resistance in pathogenic bacteria.
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              Call of the wild: antibiotic resistance genes in natural environments.

              Antibiotic-resistant pathogens are profoundly important to human health, but the environmental reservoirs of resistance determinants are poorly understood. The origins of antibiotic resistance in the environment is relevant to human health because of the increasing importance of zoonotic diseases as well as the need for predicting emerging resistant pathogens. This Review explores the presence and spread of antibiotic resistance in non-agricultural, non-clinical environments and demonstrates the need for more intensive investigation on this subject.
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                Author and article information

                Contributors
                Journal
                Comput Struct Biotechnol J
                Comput Struct Biotechnol J
                Computational and Structural Biotechnology Journal
                Research Network of Computational and Structural Biotechnology
                2001-0370
                29 December 2020
                2021
                29 December 2020
                : 19
                : 586-599
                Affiliations
                Faculty of Environmental Sciences, Technische Universität Dresden, Pienner Str. 8, D-01737 Tharandt, Germany
                Article
                S2001-0370(20)30552-3
                10.1016/j.csbj.2020.12.027
                7807137
                33510864
                d52e4211-cd31-49af-9b46-433a1db3f17a
                © 2020 The Author(s)

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 1 September 2020
                : 16 December 2020
                : 20 December 2020
                Categories
                Review

                plasmid ecology,antibiotic resistance,horizontal gene transfer,fitness,agent-based modeling,simulation model,individual heterogeneity,evolution,biotic interactions

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