Multi-locus sequence typing: a tool for global epidemiology

doi:10.1016/j.tim.2003.08.006

Trends in Microbiology

Volume 11, Issue 10, October 2003, Pages 479-487

https://doi.org/10.1016/j.tim.2003.08.006 Get rights and content

Abstract

The characterization of pathogenic isolates plays a pivotal role in the epidemiology of infectious diseases, generating the information necessary for identifying, tracking, and intervening against disease outbreaks. In 1998 multi-locus sequence typing (MLST) was proposed as a nucleotide sequence-based approach that could be applied to many bacterial pathogens. It combined developments in high-throughput sequencing and bioinformatics with established population genetics techniques to provide a portable, reproducible, and scalable typing system that reflected the population and evolutionary biology of bacterial pathogens. MLST schemes have been developed for a variety of procaryotic and eucaryotic pathogens and the data generated have contributed to both epidemiological surveillance and fundamental studies of pathogen biology.

Section snippets

Characterization of bacterial isolates

Bacterial characterization relies on distinguishing genetic variation among isolates. Early successes with enteric bacteria, particularly the Kauffmann–White scheme for Salmonella enterica, established phenotypic, specifically serological, typing as the principal approach to isolate differentiation [4]. Many of the schemes subsequently developed were extended following the advent of monoclonal antibodies (MAbs). Immunological typing schemes, however, can have drawbacks including: a reliance on

Design of multi-locus sequence typing systems

There are three elements to the design of a new MLST system: the choice of the isolates to be used in the initial evaluation; the choice of the genetic loci to be characterized; and the design of primers for gene amplification and nucleotide sequence determination. It is advisable to assemble a diverse isolate collection on the basis of existing typing information or epidemiological data. This should comprise around 100 isolates (95 is a good number if high-throughput sequencing in 96-well

Isolate characterization using MLST via the internet

The aim of the original MLST scheme [3] was to provide access to the data using the internet, and to enhance clinical diagnosis, epidemiological monitoring, and population studies. MLST websites are virtual isolate collections (for example, http://neisseria.org/mlst/, other sites can also be accessed through http://www.mlst.net). The databases are specialized and distinct from sequence depositories such as GenBank (http://www.ncbi.nlm.nih.gov/Genbank/index.html), both in their organization and

Interpreting MLST data: the clonal complex model

The clonal complex, a concept first introduced for bacteria to describe populations of N. meningitidis analysed by MLEE [26], has proved to be valuable in analysing many MLST datasets 3, 14, 27. A clonal complex comprises genetically related, but not identical, bacteria. Currently there is no formal definition of the clonal complex, but for most MLST datasets a pragmatic approach, based on genetic and microbiological criteria, produces robust clonal complex assignments which are useful for

Applications and limitations of MLST data

MLST is increasingly applied as a routine typing tool that enables international comparison of isolates 31, 32, 33, 34, 35, 36. It has been applied to problems as diverse as the emergence of antibiotic-resistant variants 29, 37, the association of particular genotypes with virulence [38] or antigenic characteristics [39], and the global spread of disease caused by novel variants [40]. In addition to these medically motivated epidemiological analyses, MLST data have been exploited in

Conclusions

In December 2002, 100 delegates from 12 countries attended an international workshop on MLST at Hinxton Hall Conference Centre, UK, providing a forum for the discussion of recent conceptual and technical advances in MLST. In a 3-day programme the current status of many MLST schemes and their public health applications were discussed. The breadth of the programme, combined with the increasing number of schemes currently published 3, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or in development,

Acknowledgements

The authors are funded by the Wellcome Trust. MCJM is a Wellcome Trust Senior Research Fellow. We thank the many colleagues who have collaborated so effectively with us on MLST projects over the years.

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Trends in Microbiology

Multi-locus sequence typing: a tool for global epidemiology

Abstract

Section snippets

Characterization of bacterial isolates

Design of multi-locus sequence typing systems

Isolate characterization using MLST via the internet

Interpreting MLST data: the clonal complex model

Applications and limitations of MLST data

Conclusions

Acknowledgements

Res. Microbiol.

Trends Microbiol.

Trends Microbiol.

Infect. Genet. Evol.

Curr. Opin. Microbiol.

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A surfeit of YATMs?

J. Clin. Microbiol.

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Proc. Natl. Acad. Sci. U. S. A.

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