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  • Review Article
  • Published:

Transforming clinical microbiology with bacterial genome sequencing

Nature Reviews Genetics volume 13, pages 601–612 (2012)Cite this article

Subjects

Key Points

  • Whole-genome sequencing of bacterial isolates is becoming more and more widespread, paving the way for a transformation of many current procedures in clinical microbiology.

  • Identifying the species of an isolate is currently a complex laboratory process. A few methods have already been proposed for doing this using the genome sequence, which could result in a re-evaluation of the bacterial species concept.

  • Testing antibiotic resistance properties is often crucial for determining the appropriate treatment. As resistance is encoded by specific genes, this susceptibility assessment could be performed in silico using the genome sequence.

  • The same is true for determining virulence properties of a strain, but with the difference that correlations between the genotype and phenotype is often more complex (involving several genes) than for resistance. However, association-mapping techniques can be used to detect such complex correlations, leading to a better understanding of pathogenicity.

  • Several studies have already demonstrated the great potential of whole-genome sequencing in epidemiological investigations. These have so far been carried out after the course of an outbreak. In the future, with improving technology, this could be carried on an ongoing basis to detect epidemiological risks as they arise and react accordingly.

  • Bacteria culturing is a pre-requirement even for whole-genome sequencing as it is currently carried out. This represents an important bottleneck as some bacteria are slow-growing and others cannot be cultured. Metagenomics approaches could provide a solution to this long-standing issue.

Abstract

Whole-genome sequencing of bacteria has recently emerged as a cost-effective and convenient approach for addressing many microbiological questions. Here, we review the current status of clinical microbiology and how it has already begun to be transformed by using next-generation sequencing. We focus on three essential tasks: identifying the species of an isolate, testing its properties, such as resistance to antibiotics and virulence, and monitoring the emergence and spread of bacterial pathogens. We predict that the application of next-generation sequencing will soon be sufficiently fast, accurate and cheap to be used in routine clinical microbiology practice, where it could replace many complex current techniques with a single, more efficient workflow.

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Figure 1: Principles of current processing of bacterial pathogens.
Figure 2: Hypothetical workflow based on whole-genome sequencing.

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Acknowledgements

D.W.C. and T.A.E.P. are part-funded by the UK National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and are NIHR Senior Investigators. X.D., D.J.W. and R.B. are funded by the UK Clinical Reasearch Collaboration. We thank J. Paul for helpful advice and suggestions.

Author information

Authors and Affiliations

  1. Department of Statistics, University of Oxford, 1 South Parks Road, Oxford, OX1 3TG, UK

    Xavier Didelot & Rory Bowden

  2. Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK

    Rory Bowden & Daniel J. Wilson

  3. NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, OX3 9DU, UK

    Rory Bowden, Tim E. A. Peto & Derrick W. Crook

  4. Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK

    Daniel J. Wilson, Tim E. A. Peto & Derrick W. Crook

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  1. Xavier Didelot
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Correspondence to Derrick W. Crook.

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Competing interests

Derrick W. Crook and Tim E. A. Peto are part-funded by the UK National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and are NIHR Senior Investigators. Xavier Didelot, Daniel J. Wilson and Rory Bowden are funded by the UK Clinical Reasearch Collaboration. This funding supports translational research for implementing genomic sequencing into clinical microbiology practice.

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FURTHER INFORMATION

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Glossary

Escherichia coli

A common inhabitant of the guts of many animals, but some strains can cause serious food poisoning, as reminded by the 2011 outbreak in Germany.

Mycobacterium tuberculosis

The causative agent of tuberculosis, it infects approximately one-third of the human population and claims over one million lives per year, making it the most deadly bacterial pathogen of humans.

Staphylococcus aureus

Found as a harmless colonizer of the skin in ~20% of the human population; it can cause life-threatening symptoms and be resistant to some antibiotics (for example, methicillin-resistant S. aureus (MRSA)).

Staphylococcus epidermidis

A normal part of the human skin flora; it can become pathogenic if introduced into deeper tissues following surgery.

16S ribosomal RNA gene

The 16S ribosomal RNA genes are transcribed into the 16S ribosomal RNA molecule, which is a major component of the bacterial small ribosomal subunit. The strong sequence conservation of this molecule makes it ideal for detecting large evolutionary distances between two organisms.

Minimum inhibitory concentration

(MIC). The minimum concentration of an antibiotic that is sufficient to inhibit growth of a bacterial culture.

Clostridium difficile

A leading cause of diarrhoea and more severe conditions, especially in the elderly following disruption of the normal gut flora through the use of antibiotics.

Serotyping

In this context, the classification of bacteria on the basis of their surface antigens.

Haemophilus influenzae

Responsible for a wide range of clinical diseases (but not influenza, as originally thought and as the name might still suggest) especially in young children, it was the first free living organism to have its genome completely sequenced.

Streptococcus pneumoniae

A major cause of pneumonia, it can also cause various other severe conditions and has recently developed resistance to some antibiotics. It causes ~1 million deaths per year, mostly in children.

Neisseria meningitidis

A commensal inhabitant of the nasopharynx in up to one-quarter of the human population; it occasionally gets into the blood, resulting in >100,000 deaths per year through meningitis and septicaemia.

Campylobacter jejuni

A natural colonizer of the digestive tracts of many birds and cattle; it is typically transmitted to humans by ingestion of contaminated food and results in severe diarrhoeal diseases.

Vibrio cholerae

The agent of cholera is transmitted via contaminated waters and can cause death through dehydration. It caused millions of deaths in Europe in the ninteenth century but has since mostly disappeared from industrialized countries. It still claims >100,000 lives per year in developing countries.

Salmonella enterica subsp. enterica serovar Typhi

All Salmonella cause disease, but the Typhi lineage is the main causative agent of typhoid fever, which claims hundreds of thousands of lives per annum.

New Delhi metallo-β-lactamase-1

An enzyme that confers extensive antibiotic resistance; first characterized in 2008.

Chlamydia trachomatis

The cause of >100 million sexually transmitted infections annually, as well as trachoma, which is an infection of the eye that can result in blindness.

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Didelot, X., Bowden, R., Wilson, D. et al. Transforming clinical microbiology with bacterial genome sequencing. Nat Rev Genet 13, 601–612 (2012). https://doi.org/10.1038/nrg3226

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