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      A mathematician’s guide to plasmids: an introduction to plasmid biology for modellers

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          Abstract

          Plasmids, extrachromosomal DNA molecules commonly found in bacterial and archaeal cells, play an important role in bacterial genetics and evolution. Our understanding of plasmid biology has been furthered greatly by the development of mathematical models, and there are many questions about plasmids that models would be useful in answering. In this review, we present an introductory, yet comprehensive, overview of the biology of plasmids suitable for modellers unfamiliar with plasmids who want to get up to speed and to begin working on plasmid-related models. In addition to reviewing the diversity of plasmids and the genes they carry, their key physiological functions, and interactions between plasmid and host, we also highlight selected plasmid topics that may be of particular interest to modellers and areas where there is a particular need for theoretical development. The world of plasmids holds a great variety of subjects that will interest mathematical biologists, and introducing new modellers to the subject will help to expand the existing body of plasmid theory.

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            Mobility of plasmids.

            Plasmids are key vectors of horizontal gene transfer and essential genetic engineering tools. They code for genes involved in many aspects of microbial biology, including detoxication, virulence, ecological interactions, and antibiotic resistance. While many studies have decorticated the mechanisms of mobility in model plasmids, the identification and characterization of plasmid mobility from genome data are unexplored. By reviewing the available data and literature, we established a computational protocol to identify and classify conjugation and mobilization genetic modules in 1,730 plasmids. This allowed the accurate classification of proteobacterial conjugative or mobilizable systems in a combination of four mating pair formation and six relaxase families. The available evidence suggests that half of the plasmids are nonmobilizable and that half of the remaining plasmids are conjugative. Some conjugative systems are much more abundant than others and preferably associated with some clades or plasmid sizes. Most very large plasmids are nonmobilizable, with evidence of ongoing domestication into secondary chromosomes. The evolution of conjugation elements shows ancient divergence between mobility systems, with relaxases and type IV coupling proteins (T4CPs) often following separate paths from type IV secretion systems. Phylogenetic patterns of mobility proteins are consistent with the phylogeny of the host prokaryotes, suggesting that plasmid mobility is in general circumscribed within large clades. Our survey suggests the existence of unsuspected new relaxases in archaea and new conjugation systems in cyanobacteria and actinobacteria. Few genes, e.g., T4CPs, relaxases, and VirB4, are at the core of plasmid conjugation, and together with accessory genes, they have evolved into specific systems adapted to specific physiological and ecological contexts.
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              Plasmids and the spread of resistance.

              Plasmids represent one of the most difficult challenge for counteracting the dissemination of antimicrobial resistance. They contribute to the spread of relevant resistance determinants, promoting horizontal gene transfer among unrelated bacteria. Undistinguishable plasmids were identified in unrelated bacterial strains isolated at huge geographically distant area, with no apparent epidemiological links. These plasmids belong to families that are largely prevalent in naturally occurring bacteria, usually carry multiple physically linked genetic determinants, conferring resistance to different classes of antibiotics simultaneously. Plasmids also harbour virulence factors and addiction systems, promoting their stability and maintenance in the bacterial host, in different environmental conditions. The characteristics of the most successful plasmids that were at the origin of the spread of carbapenemase, expanded-spectrum β-lactamase, and plasmid-mediated quinolone resistance genes are discussed in this review. Copyright © 2013 Elsevier GmbH. All rights reserved.
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                Author and article information

                Journal
                Microbiology (Reading)
                Microbiology (Reading)
                micro
                micro
                Microbiology
                Microbiology Society
                1350-0872
                1465-2080
                2023
                28 July 2023
                28 July 2023
                : 169
                : 7
                : 001362
                Affiliations
                [ 1] Research Group Stochastic Evolutionary Dynamics, Department of Theoretical Biology, Max Planck Institute for Evolutionary Biology , Plön, Germany
                Author notes
                *Correspondence: Ian Dewan, dewan@ 123456evolbio.mpg.de
                Author information
                https://orcid.org/0000-0001-8964-3800
                https://orcid.org/0000-0001-9435-2813
                Article
                001362
                10.1099/mic.0.001362
                10433428
                37505810
                3461c98f-83b7-4c2b-85c2-37a91b6fadfb
                © 2023 The Authors

                This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.

                History
                : 26 March 2023
                : 03 July 2023
                Funding
                Funded by: Deutsche Forschungsgemeinschaft
                Award ID: 400993799
                Award Recipient : HildegardUecker
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                plasmids,modelling,bacterial evolution,mobile genetic elements,horizontal gene transfer

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