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'Add, stir and reduce': Yersinia spp. as model bacteria for pathogen evolution

Nature Reviews Microbiology volume 14, pages 177–190 (2016)Cite this article

Subjects

Key Points

  • The evolution of mammalian pathogenesis in the Yersinia genus has occurred in different lineages in parallel through a balanced mixture of gene gain and gene loss events.

  • Only by sequencing pathogenic and non-pathogenic representatives from an entire bacterial genus can such observations be made.

  • The parallel evolution of pathogenesis is even shared with enteric pathogens outside of the Yersinia genus, notably in the Salmonella genus.

  • Gene loss events lead to niche restriction owing to a reduction in metabolic flexibility, which is often seen in lineages that evolve a more acutely pathogenic phenotype.

  • The potential of loss of fitness from the expression of genes acquired in gene gain events is mediated by the transcriptional silencing of, or fine control of, these acquired elements by ancestral regulons that are regulated by factors such as RovA and H-NS.

Abstract

Pathogenic species in the Yersinia genus have historically been targets for research aimed at understanding how bacteria evolve into mammalian pathogens. The advent of large-scale population genomic studies has greatly accelerated the progress in this field, and Yersinia pestis, Yersinia pseudotuberculosis and Yersinia enterocolitica have once again acted as model organisms to help shape our understanding of the evolutionary processes involved in pathogenesis. In this Review, we highlight the gene gain, gene loss and genome rearrangement events that have been identified by genomic studies in pathogenic Yersinia species, and we discuss how these findings are changing our understanding of pathogen evolution. Finally, as these traits are also found in the genomes of other species in the Enterobacteriaceae, we suggest that they provide a blueprint for the evolution of enteropathogenic bacteria.

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Figure 1: Comparison of the RovA–YmoA regulons of Yersinia enterocolitica, Yersinia pseudotuberculosis and Yersinia pestis.
Figure 2: Gene loss in the emergence of Yersinia pestis from Yersinia pseudotuberculosis.
Figure 3: Gene gain and gene loss in Yersinia enterocolitica.
Figure 4: Enteropathogenic Enterobacteriaceae use the cob, pdu and ttr operons to outcompete the normal intestinal microbiota during mammalian infection.
Figure 5: Key gene gain and gene loss events in the evolution of mammalian pathogenesis in the Yersinia genus.

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Acknowledgements

A.M. acknowledges funding from the UK Department for Environment, Food and Rural Affairs (Defra), B.W.W. acknowledges funding from Defra and the UK Biotechnology and Biological Sciences Research Council (BBSRC) and N.R.T. acknowledges funding from the Wellcome Trust (core award 098051). The authors thank their respective funding bodies for supporting the Yersinia spp. research in their laboratories. The authors also thank Nottingham Trent University for their generous funding through the Vice Chancellor's Researcher Development Scheme for the Ph.D. research of S.R. on evolution in Yersinia species.

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Authors and Affiliations

  1. Pathogen Research Group, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS, UK

    Alan McNally

  2. Pathogen Genomics, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK

    Nicholas R. Thomson

  3. Department of Medicine, University of Cambridge, Box 157 Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, UK

    Sandra Reuter

  4. Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK

    Brendan W. Wren

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  1. Alan McNally
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Correspondence to Alan McNally.

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PowerPoint slides

Glossary

Type III secretion systems

(T3SSs). Needle-like protein complexes used by some bacteria to export proteins. T3SSs are often responsible for the translocation of bacterial effector proteins from pathogenic or symbiotic bacteria directly into the cytoplasm of a host cell.

Salmonids

Fish from the Salmonidae family, which includes salmon and trout.

Phylogenomic analysis

The analysis of evolutionary trees created from whole- genome sequences. In contrast to the analysis of single-gene phylogenetic markers, such as the ribosomal 16S gene, phylogenomic analysis can infer high-resolution evolutionary patterns.

Integrons

Cassettes of genes incorporated into loci encoding a site-specific recombinase, a recombination recognition site and a promoter. Integrons are often found in conjunction with other genes, such as antibiotic resistance genes.

Genomic islands

Large genetic regions, acquired by horizontal gene transfer, that encode one or more functional groups of genes. They are frequently associated with tRNA genes, are flanked by repeat structures and contain mobility genes encoding integrases or transposases that are required for chromosomal integration and excision.

Horizontal gene transfer

The transfer of DNA, frequently cassettes of genes, between organisms.

Transduction

The phage-mediated transfer of DNA, frequently cassettes of genes, between organisms.

Natural transformation

The direct uptake of DNA from the environment and the incorporation of this genetic material into the chromosome by competent cells.

Conjugation

The transfer of DNA — usually plasmids — between organisms through direct cell-to-cell contact or through a bridge that forms between cells.

Yersinia outer proteins

(Yops). A set of effector proteins secreted by the Ysc type III secretion system (T3SS). Yops are injected into phagocytic cells, in which they inhibit the production of pro-inflammatory cytokines and induce apoptosis of the infected cell.

Multi-locus sequence typing

(MLST). A strain typing technique based on the allele profiling of seven housekeeping genes conserved in a given species.

Accessory gene pool

The set of genes that have been shown to be differentially present in individual genomes within a species or genus.

Yersinia murine toxin

(Ymt). First characterized as a determinant of lethality in mice but now known to have a crucial role in the ability of Yersinia pestis to survive in fleas.

F1 capsular protein

Protein antigen found on the surface of pathogenic Yersinia spp. that is thought to modulate the targeting of bacteria to sites of infection.

Pla

A protease found in Yersinia pestis that is encoded on a Y. pestis-specific plasmid. Pla is required for pneumonic infection.

Integrative and conjugative element

(ICE). A class of bacterial mobile elements that uses self-encoded integrase and excision factors for excision and transfer to a donor cell.

Extraintestinal pathogenic Escherichia coli

(ExPEC). Strains of Escherichia coli that can asymptomatically colonize the mammalian intestinal tract but cause disease in sites such as the urinary tract, blood stream or meninges.

Regulons

Sets of genes in which each set is under the control of a common regulatory system.

MarR/SlyA

A family of transcriptional regulators found in bacteria. Most of these regulators activate transcription by alleviating histone-like nucleoid structuring protein (H-NS)-mediated repression.

Promiscuous regulatory system

A set of promiscuous regulators and cognate regulon; these promiscuous regulators assume transcriptional control of numerous genes that do not come under fine-scale environmental control.

Two-component regulatory system

A bacterial sensor–kinase system (composed of an outer membrane sensor and a response regulator) that regulates gene expression in response to a specific environmental stimulus.

Insertion sequence element

An insertion sequence element is the simplest type of bacterial transposable element and encodes only the gene required for its own transposition, flanked by insertion sequence repeats.

Cyclic di-GMP

A secondary messenger molecule used in bacterial signal transduction to modulate gene expression in response to environmental perturbations.

Phase-variable mutation

A reversible mutation that can switch from wild-type to mutant, or from mutant to wild-type, in cell progeny.

Galliforme birds

An order of approximately 290 bird species that are best described as fowl-like or poultry-like.

Phenotype microarrays

High-throughput, automated assays that determine the ability of living cells to metabolize metabolic substrates.

Palaeomicrobiology

The study of historical infectious disease or microbiota by recovering DNA from ancient human (or other host) remains.

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McNally, A., Thomson, N., Reuter, S. et al. 'Add, stir and reduce': Yersinia spp. as model bacteria for pathogen evolution. Nat Rev Microbiol 14, 177–190 (2016). https://doi.org/10.1038/nrmicro.2015.29

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