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Going around in circles: virulence plasmids in enteric pathogens

Nature Reviews Microbiology volume 16, pages 484–495 (2018)Cite this article

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Abstract

Plasmids have a major role in the development of disease caused by enteric bacterial pathogens. Virulence plasmids are usually large (>40 kb) low copy elements and encode genes that promote host–pathogen interactions. Although virulence plasmids provide advantages to bacteria in specific conditions, they often impose fitness costs on their host. In this Review, we discuss virulence plasmids in Enterobacteriaceae that are important causes of diarrhoea in humans, Shigella spp., Salmonella spp., Yersinia spp and pathovars of Escherichia coli. We contrast these plasmids with those that are routinely used in the laboratory and outline the mechanisms by which virulence plasmids are maintained in bacterial populations. We highlight examples of virulence plasmids that encode multiple mechanisms for their maintenance (for example, toxin–antitoxin and partitioning systems) and speculate on how these might contribute to their propagation and success.

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Fig. 1: General features of laboratory and virulence plasmids.
Fig. 2: The virulence plasmids of Shigella flexneri (pWR501) and Salmonella enterica subsp. enterica serovar Typhimurium (pSLT2).
Fig. 3: The genetic structure of replicons in virulence plasmids.
Fig. 4: Partitioning systems in virulence plasmids.
Fig. 5: Crosstalk between par1 and par2 in pB171.
Fig. 6: Summary of the principal elements that influence the biology of virulence plasmids.

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Acknowledgements

Work in C.M.T.’s laboratory is supported by the Wellcome Trust and the Biotechnology and Biological Sciences Research Council. G.P. is the recipient of a Medical Research Council PhD studentship and is supported by the E.P. Abraham Trust.

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  1. Sir William Dunn School of Pathology, University of Oxford, Oxford, UK

    Giulia Pilla & Christoph M. Tang

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G.P. researched the data for the article. G.P. and C.M.T. substantially contributed to discussion of content, wrote the article and reviewed and edited the manuscript before submission.

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Correspondence to Christoph M. Tang.

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Glossary

Plasmid copy number

Average number of plasmid copies per cell.

Enteropathogens

Pathogenic bacteria that infect the intestinal tract of humans and animals, causing diarrhoea, gastroenteritis and localized lymphadenitis.

Pathotypes

Classes of pathogenic bacteria belonging to the same species that are characterized by their capacity to cause specific diseases through a defined set of virulence factors.

Haemolytic uraemic syndrome

(HUS). A disease characterized by acute renal failure, haemolytic anaemia (that is, inappropriate destruction of erythrocytes) and thrombocytopenia (low levels of circulating platelets).

Prototypic plasmid

Some of the first discovered plasmids that were used as models to study plasmid biology.

Yersiniosis

An acute gastrointestinal infection caused by Yersinia enterocolitica or Yersinia pseudotuberculosis that is characterized by enteritis, diarrhoea and fever. It is occasionally associated with more severe complications, such as ileitis, septicaemia and acute arthritis.

Pathogenicity island

(PAI). A region on a chromosome or plasmid that contains clusters of virulence genes that are often flanked by mobile genetic elements or direct repeats that could mediate the mobility of the entire region.

Pyroptosis

A mechanism of inflammatory cell death characterized by a rapid disruption of the plasmalemma driven by stimulation of the pore-forming activity of gasdermin D and accompanied by the concomitant release of pro-inflammatory cytokines, such as IL-1β and IL-18, and chromatin fragmentation.

Insertion sequences

Short transposable DNA elements that can move within the same DNA molecule or between different DNA molecules. They are composed only of genes encoding proteins involved in mobility, such as transposases and regulatory elements. Distinct from transposons, insertion sequences do not carry any accessory genes (for example, those encoding antibiotic resistance).

Phosphothreonine lyase

An enzyme that catalyses the irreversible removal of a phosphate group from a phosphorylated threonine residue.

Plasmid incompatibility

A phenomenon whereby two plasmids cannot coexist in the same bacterial cell. It occurs when plasmids share one or more elements that control their replication, partitioning or copy number. On the basis of sequence homology, plasmids are classified into different incompatibility groups, so plasmids belonging to the same group are incompatible with each other but are compatible with plasmids in different incompatibility groups.

Replicon

A DNA region that includes genes that are sufficient for plasmid replication and copy number control and where replication is initiated. Depending on the sequence of the replicon, plasmids are classified into different replicon groups.

Theta replication

A mechanism of DNA replication in which the synthesis of the leading and lagging DNA strands is coupled, leading to the formation of theta-shaped intermediates.

DnaA boxes

Short stretches of DNA that are bound by the chromosomal replication initiator protein DnaA. The interaction between DnaA and DnaA boxes localized at the origin is essential to unwind DNA before the start of DNA replication.

Co-integration

A phenomenon that causes two circular plasmids to combine, maintaining the sequence of each plasmid intact, thus producing a single plasmid from two separate plasmids.

Nucleoside triphosphatase

(NTPase). A family of enzymes that catalyses the hydrolysis of a nucleoside triphosphate (NTP) to a nucleoside diphosphate (NDP). The reaction releases energy, often inducing a conformational change in protein structure that allows the protein to drive other chemical reactions.

DNA par sites

Centromere-like DNA sequences that often contain repeated sequences and are specifically bound by centromere-binding proteins (CBPs); they are required in cis for plasmid partitioning and form the partitioning complex when associated with CBP.

Centromere-binding protein

(CBP). A family of proteins that specifically bind to centromere-like DNA sites, which can contain multiple CBP-bound sequences and, therefore, be recognized by multiple CBPs, leading to the formation of nucleoprotein complexes.

Walker-type ATPases

Adenosine triphosphatases (ATPases) that are characterised by Walker motifs, amino acid sequences that have an important role in ATP binding and hydrolysis.

Actin-like ATPase

A family of ATPases that contain ATP-binding domains that are homologous to those present in actin. For ParM, the structure of the ATPase resembles that of actin, implying that, like actin, ParM can form filaments.

DNA gyrase

A group of essential enzymes defined as topoisomerases that are responsible for the ATP-dependent conversion of relaxed DNA into a negatively supercoiled form.

Poly-cistronic operon

An operon containing multiple genes that are transcribed as a single mRNA from which the proteins are translated.

Resolvase

A large family of site-specific recombinases. Resolvases have an essential role in resolving plasmid multimers into monomers.

mRNA interferase

A class of endoribonucleases that cleave mRNA at a specific site, blocking protein synthesis.

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Pilla, G., Tang, C.M. Going around in circles: virulence plasmids in enteric pathogens. Nat Rev Microbiol 16, 484–495 (2018). https://doi.org/10.1038/s41579-018-0031-2

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