Plasmid classification in an era of whole-genome sequencing: Application in studies of antibiotic resistance epidemiology

Alex Orlek*, Nicole Stoesser, Muna F. Anjum, Michel Doumith, Matthew J. Ellington, Tim Peto, Derrick Crook, Neil Woodford, A. Sarah Walker, Hang Phan, Anna E. Sheppard

*Corresponding author for this work

Research output: Contribution to journalShort surveypeer-review

86 Citations (Scopus)

Abstract

Plasmids are extra-chromosomal genetic elements ubiquitous in bacteria, and commonly transmissible between host cells. Their genomes include variable repertoires of 'accessory genes,' such as antibiotic resistance genes, as well as 'backbone' loci which are largely conserved within plasmid families, and often involved in key plasmid-specific functions (e.g., replication, stable inheritance, mobility). Classifying plasmids into different types according to their phylogenetic relatedness provides insight into the epidemiology of plasmid-mediated antibiotic resistance. Current typing schemes exploit backbone loci associated with replication (replicon typing), or plasmid mobility (MOB typing). Conventional PCR-based methods for plasmid typing remain widely used. With the emergence of whole-genome sequencing (WGS), large datasets can be analyzed using in silico plasmid typing methods. However, short reads from popular high-throughput sequencers can be challenging to assemble, so complete plasmid sequences may not be accurately reconstructed. Therefore, localizing resistance genes to specific plasmids may be difficult, limiting epidemiological insight. Long-read sequencing will become increasingly popular as costs decline, especially when resolving accurate plasmid structures is the primary goal. This review discusses the application of plasmid classification in WGS-based studies of antibiotic resistance epidemiology; novel in silico plasmid analysis tools are highlighted. Due to the diverse and plastic nature of plasmid genomes, current typing schemes do not classify all plasmids, and identifying conserved, phylogenetically concordant genes for subtyping and phylogenetics is challenging. Analyzing plasmids as nodes in a network that represents gene-sharing relationships between plasmids provides a complementary way to assess plasmid diversity, and allows inferences about horizontal gene transfer to be made.

Original languageEnglish
Article number182
JournalFrontiers in Microbiology
Volume8
Issue numberFEB
DOIs
Publication statusPublished - 9 Feb 2017

Bibliographical note

Funding Information:
The research was funded by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at Oxford University in partnership with Public Health England (PHE) [grant HPRU-2012-10041]. The report presents independent research funded by the National Institute for Health Research. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, the Department of Health or Public Health England. NS is currently funded through an NIHR/University of Oxford Academic Clinical Lectureship. TP is an NIHR Senior Investigator.

Publisher Copyright:
© 2017 Orlek, Stoesser, Anjum, Doumith, Ellington, Peto, Crook, Woodford, Walker, Phan and Sheppard.

Keywords

  • Antibiotic resistance
  • Genomic epidemiology
  • Network analysis
  • Plasmid typing
  • Whole-genome sequencing

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