title: Ordering the mob: Insights into replicon and MOB typing schemes from analysis of a curated dataset of publicly available plasmids.
abstract: Plasmid typing can provide insights into the epidemiology and transmission of plasmid-mediated antibiotic resistance. The principal plasmid typing schemes are replicon typing and MOB typing, which utilize variation in replication loci and relaxase proteins respectively. Previous studies investigating the proportion of plasmids assigned a type by these schemes ('typeability') have yielded conflicting results; moreover, thousands of plasmid sequences have been added to NCBI in recent years, without consistent annotation to indicate which sequences represent complete plasmids. Here, a curated dataset of complete Enterobacteriaceae plasmids from NCBI was compiled, and used to assess the typeability and concordance of in silico replicon and MOB typing schemes. Concordance was assessed at hierarchical replicon type resolutions, from replicon family-level to plasmid multilocus sequence type (pMLST)-level, where available. We found that 85% and 65% of the curated plasmids could be replicon and MOB typed, respectively. Overall, plasmid size and the number of resistance genes were significant independent predictors of replicon and MOB typing success. We found some degree of non-concordance between replicon families and MOB types, which was only partly resolved when partitioning plasmids into finer-resolution groups (replicon and pMLST types). In some cases, non-concordance was attributed to ambiguous boundaries between MOBP and MOBQ types; in other cases, backbone mosaicism was considered a more plausible explanation. β-lactamase resistance genes tended not to show fidelity to a particular plasmid type, though some previously reported associations were supported. Overall, replicon and MOB typing schemes are likely to continue playing an important role in plasmid analysis, but their performance is constrained by the diverse and dynamic nature of plasmid genomes.
authors.affiliation: Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK; NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, University of Oxford, Oxford, UK. Electronic address: alex.orlek@wolfson.ox.ac.uk.
authors.forename: Alex
authors.initials: A
authors.lastname: Orlek
authors.affiliation: Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK; NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, University of Oxford, Oxford, UK.
authors.forename: Hang
authors.initials: H
authors.lastname: Phan
authors.affiliation: Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK; NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, University of Oxford, Oxford, UK.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Sheppard
authors.affiliation: Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, National Infection Service, Public Health England, London, UK.
authors.forename: Michel
authors.initials: M
authors.lastname: Doumith
authors.affiliation: NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, University of Oxford, Oxford, UK; Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, National Infection Service, Public Health England, London, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Ellington
authors.affiliation: Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK; NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, University of Oxford, Oxford, UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Peto
authors.affiliation: Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK; NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, University of Oxford, Oxford, UK.
authors.forename: Derrick
authors.initials: D
authors.lastname: Crook
authors.affiliation: Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK; NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, University of Oxford, Oxford, UK.
authors.forename: A Sarah
authors.initials: AS
authors.lastname: Walker
authors.affiliation: NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, University of Oxford, Oxford, UK; Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, National Infection Service, Public Health England, London, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Woodford
authors.affiliation: NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, University of Oxford, Oxford, UK; Department of Bacteriology, Animal and Plant Health Agency, Addlestone, UK.
authors.forename: Muna F
authors.initials: MF
authors.lastname: Anjum
authors.affiliation: Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: Nicole
authors.initials: N
authors.lastname: Stoesser
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D015373:Bacterial Typing Techniques; D030541:Databases, Genetic; D066264:Datasets as Topic; D004706:Endodeoxyribonucleases / Q000235:genetics* / Q000378:metabolism; D004755:Enterobacteriaceae / Q000145:classification* / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D009030:Mosaicism; D010802:Phylogeny; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D012093:Replicon; D018440:beta-Lactam Resistance / Q000235:genetics; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism; D047090:beta-Lactams / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D047090:beta-Lactams; D004706:Endodeoxyribonucleases; C120220:MobM protein, bacteria; D001618:beta-Lactamases
keywords: Antibiotic resistance; MOB typing; Plasmid database; Plasmid multilocus sequence typing; Replicon typing