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.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Stone, A. B. R factors: plasmids conferring resistance to antibacterial agents. Sci. Prog. 62, 89–101 (1975).
Yang, F. et al. Genome dynamics and diversity of Shigella species, the etiologic agents of bacillary dysentery. Nucleic Acids Res. 33, 6445–6458 (2005).
Kaper, J. B., Nataro, J. P. & Mobley, H. L. Pathogenic Escherichia coli. Nat. Rev. Microbiol. 2, 123–140 (2004).
Sansonetti, P. J., d’Hauteville, H., Ecobichon, C. & Pourcel, C. Molecular comparison of virulence plasmids in Shigella and enteroinvasive Escherichia coli. Ann. Microbiol. 134A, 295–318 (1983).
Lan, R., Lumb, B., Ryan, D. & Reeves, P. R. Molecular evolution of large virulence plasmid in Shigella clones and enteroinvasive Escherichia coli. Infect. Immun. 69, 6303–6309 (2001).
Clements, A., Young, J. C., Constantinou, N. & Frankel, G. Infection strategies of enteric pathogenic Escherichia coli. Gut Microbes 3, 71–87 (2012).
Johnson, T. J. & Nolan, L. K. Pathogenomics of the virulence plasmids of Escherichia coli. Microbiol. Mol. Biol. Rev. 73, 750–774 (2009).
Burland, V. et al. The complete DNA sequence and analysis of the large virulence plasmid of Escherichia coli O157:H7. Nucleic Acids Res. 26, 4196–4204 (1998). This work provides insights on the structure of pO157 from EHEC E. coli O157:H7.
Nguyen, Y. & Sperandio, V. Enterohemorrhagic E. coli (EHEC) pathogenesis. Front. Cell. Infect. Microbiol. 2, 90 (2012).
Tobe, T. et al. Complete DNA sequence and structural analysis of the enteropathogenic Escherichia coli adherence factor plasmid. Infect. Immun. 67, 5455–5462 (1999). In this paper, Tobe and colleagues analyse the structure of pB171 from EPEC E. coli B171.
Froehlich, B., Parkhill, J., Sanders, M., Quail, M. A. & Scott, J. R. The pCoo plasmid of enterotoxigenic Escherichia coli is a mosaic cointegrate. J. Bacteriol. 187, 6509–6516 (2005). This paper provides an analysis of the pCoo plasmid from ETEC E. coli, demonstrating that the plasmid is a result of co-integration of two independent replicons.
Jonsson, R. et al. A novel pAA virulence plasmid encoding toxins and two distinct variants of the fimbriae of enteroaggregative Escherichia coli. Front. Microbiol. 8, 263 (2017). This study analyses the sequence of a novel pAA plasmid from EAEC E. coli, which encodes two variants of fimbriae and other new virulence genes.
Benjelloun-Touimi, Z., Si Tahar, M., Montecucco, C., Sansonetti, P. J. & Parsot, C. SepA, the 110 kDa protein secreted by Shigella flexneri: two-domain structure and proteolytic activity. Microbiology 144, 1815–1822 (1998).
Eslava, C. et al. Pet, an autotransporter enterotoxin from enteroaggregative Escherichia coli. Infect. Immun. 66, 3155–3163 (1998).
Eng, S. et al. Salmonella: A review on pathogenesis, epidemiology and antibiotic resistance. Front. Life Sci. 8, 284–293 (2015).
Rotger, R. & Casadesús, J. The virulence plasmids of Salmonella. Int. Microbiol. 2, 177–184 (1999).
Mehigh, R. J., Sample, A. K. & Brubaker, R. R. Expression of the low calcium response in Yersinia pestis. Microb. Pathog. 6, 203–217 (1989).
Funnell, E. B. & Phillips, J. G. Plasmid Biology (American Society for Microbiology Press, 2004).
Hu, P. et al. Structural organization of virulence-associated plasmids of Yersinia pestis. J. Bacteriol. 180, 5192–5202 (1998).
Nesbakken, T., Kapperud, G., Sorum, H. & Dommarsnes, K. Structural variability of 40–50 Mdal virulence plasmids from Yersinia enterocolitica. Geographical and ecological distribution of plasmid variants. Acta Pathol. Microbiol. Immunol. Scand. B 95, 167–173 (1987).
Venkatesan, M. M. & Ranallo, R. T. Live-attenuated Shigella vaccines. Expert Rev. Vaccines 5, 669–686 (2006).
Visser, L. G., Annema, A. & van Furth, R. Role of Yops in inhibition of phagocytosis and killing of opsonized Yersinia enterocolitica by human granulocytes. Infect. Immun. 63, 2570–2575 (1995).
Pfeiffer, M. L., DuPont, H. L. & Ochoa, T. J. The patient presenting with acute dysentery — a systematic review. J. Infect. 64, 374–386 (2012).
GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 388, 1459–1544 (2016).
Lima, I. F., Havt, A. & Lima, A. A. Update on molecular epidemiology of Shigella infection. Curr. Opin. Gastroenterol. 31, 30–37 (2015).
Kotloff, K. L. et al. Global burden of Shigella infections: implications for vaccine development and implementation of control strategies. Bull. World Health Organ. 77, 651–666 (1999).
Sansonetti, P. J., Kopecko, D. J. & Formal, S. B. Involvement of a plasmid in the invasive ability of Shigella flexneri. Infect. Immun. 35, 852–860 (1982).
Venkatesan, M. M. et al. Complete DNA sequence and analysis of the large virulence plasmid of Shigella flexneri. Infect. Immun. 69, 3271–3285 (2001).
Buchrieser, C. et al. The virulence plasmid pWR100 and the repertoire of proteins secreted by the type III secretion apparatus of Shigella flexneri. Mol. Microbiol. 38, 760–771 (2000).
Zychlinsky, A., Prevost, M. C. & Sansonetti, P. J. Shigella flexneri induces apoptosis in infected macrophages. Nature 358, 167–169 (1992).
Ogawa, M., Handa, Y., Ashida, H., Suzuki, M. & Sasakawa, C. The versatility of Shigella effectors. Nat. Rev. Microbiol. 6, 11–16 (2008).
Suzuki, T. et al. Differential regulation of caspase-1 activation, pyroptosis, and autophagy via Ipaf and ASC in Shigella-infected macrophages. PLoS Pathog. 3, e111 (2007).
Schuch, R. & Maurelli, A. T. Virulence plasmid instability in Shigella flexneri 2a is induced by virulence gene expression. Infect. Immun. 65, 3686–3692 (1997).
Pilla, G., McVicker, G. & Tang, C. M. Genetic plasticity of the Shigella virulence plasmid is mediated by intra- and inter-molecular events between insertion sequences. PLoS Genet. 13, e1007014 (2017). This work demonstrates that toxin–antitoxin systems on plasmids have local and global effects mediated by post-recombinational killing as well as PSK, respectively. Plasmid deletions and chromosomal integration are mediated by insertion sequences.
Brotcke Zumsteg, A., Goosmann, C., Brinkmann, V., Morona, R. & Zychlinsky, A. IcsA is a Shigella flexneri adhesin regulated by the type III secretion system and required for pathogenesis. Cell Host Microbe 15, 435–445 (2014).
Schroeder, G. N. & Hilbi, H. Molecular pathogenesis of Shigella spp.: controlling host cell signaling, invasion, and death by type III secretion. Clin. Microbiol. Rev. 21, 134–156 (2008).
Gulig, P. A. & Doyle, T. J. The Salmonella typhimurium virulence plasmid increases the growth rate of salmonellae in mice. Infect. Immun. 61, 504–511 (1993).
Fields, P. I., Swanson, R. V., Haidaris, C. G. & Heffron, F. Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent. Proc. Natl Acad. Sci. USA 83, 5189–5193 (1986).
Gulig, P. A., Doyle, T. J., Clare-Salzler, M. J., Maiese, R. L. & Matsui, H. Systemic infection of mice by wild-type but not Spv- Salmonella typhimurium is enhanced by neutralization of gamma interferon and tumor necrosis factor alpha. Infect. Immun. 65, 5191–5197 (1997).
Zhu, Y. et al. Structural insights into the enzymatic mechanism of the pathogenic MAPK phosphothreonine lyase. Mol. Cell 28, 899–913 (2007).
Haneda, T. et al. Salmonella type III effector SpvC, a phosphothreonine lyase, contributes to reduction in inflammatory response during intestinal phase of infection. Cell. Microbiol. 14, 485–499 (2012).
Boyd, E. F. & Hartl, D. L. Salmonella virulence plasmid. Modular acquisition of the spv virulence region by an F-plasmid in Salmonella enterica subspecies I and insertion into the chromosome of subspecies II, IIIa, IV and VII isolates. Genetics 149, 1183–1190 (1998).
Baumler, A. J. et al. The pef fimbrial operon of Salmonella typhimurium mediates adhesion to murine small intestine and is necessary for fluid accumulation in the infant mouse. Infect. Immun. 64, 61–68 (1996).
Baumler, A. J., Tsolis, R. M. & Heffron, F. Contribution of fimbrial operons to attachment to and invasion of epithelial cell lines by Salmonella typhimurium. Infect. Immun. 64, 1862–1865 (1996).
Heffernan, E. J., Harwood, J., Fierer, J. & Guiney, D. The Salmonella typhimurium virulence plasmid complement resistance gene rck is homologous to a family of virulence-related outer membrane protein genes, including pagC and ail. J. Bacteriol. 174, 84–91 (1992).
Heffernan, E. J. et al. Mechanism of resistance to complement-mediated killing of bacteria encoded by the Salmonella typhimurium virulence plasmid gene rck. J. Clin. Invest. 90, 953–964 (1992).
Rosselin, M. et al. Rck of Salmonella enterica, subspecies enterica serovar enteritidis, mediates zipper-like internalization. Cell Res. 20, 647–664 (2010).
Vandenbosch, J. L., Rabert, D. K., Kurlandsky, D. R. & Jones, G. W. Sequence analysis of rsk, a portion of the 95-kilobase plasmid of Salmonella typhimurium associated with resistance to the bactericidal activity of serum. Infect. Immun. 57, 850–857 (1989).
Sengupta, M. & Austin, S. Prevalence and significance of plasmid maintenance functions in the virulence plasmids of pathogenic bacteria. Infect. Immun. 79, 2502–2509 (2011).
Chattoraj, D. K. Control of plasmid DNA replication by iterons: no longer paradoxical. Mol. Microbiol. 37, 467–476 (2000).
Helinski, D. R., Toukdarian, A. E. & Novick, R. in Escherichia coli and Salmonella: Cellular and Molecular Biology 2nd edn (eds Neidhardt, F. C. et al.) 2295–2324 (ASM Press, Washington, DC, 1996).
Pinto, U. M., Pappas, K. M. & Winans, S. C. The ABCs of plasmid replication and segregation. Nat. Rev. Microbiol. 10, 755–765 (2012).
del Solar, G., Giraldo, R., Ruiz-Echevarria, M. J., Espinosa, M. & Diaz-Orejas, R. Replication and control of circular bacterial plasmids. Microbiol. Mol. Biol. Rev. 62, 434–464 (1998).
Nordstrom, K. Plasmid R1−-replication and its control. Plasmid 55, 1–26 (2006).
Cox, K. E. L. & Schildbach, J. F. Sequence of the R1 plasmid and comparison to F and R100. Plasmid 91, 53–60 (2017). This study provides a sequence analysis of prototypic plasmids, demonstrating the multiplicity of factors for replication and maintenance.
Masai, H., Kaziro, Y. & Arai, K. Definition of oriR, the minimum DNA segment essential for initiation of R1 plasmid replication in vitro. Proc. Natl Acad. Sci. USA 80, 6814–6818 (1983).
Trawick, J. D. & Kline, B. C. A two-stage molecular model for control of mini-F replication. Plasmid 13, 59–69 (1985).
Uga, H., Matsunaga, F. & Wada, C. Regulation of DNA replication by iterons: an interaction between the ori2 and incC regions mediated by RepE-bound iterons inhibits DNA replication of mini-F plasmid in Escherichia coli. EMBO J. 18, 3856–3867 (1999).
Willetts, N. & Skurray, R. in Escherichia coli and Salmonella: Cellular and Molecular Biology 2nd edn (eds Neidhardt, F. C. et al.) 1110–1133 (ASM Press, Washington, DC, 1996).
Saadi, S., Maas, W. K., Hill, D. F. & Bergquist, P. L. Nucleotide sequence analysis of RepFIC, a basic replicon present in IncFI plasmids P307 and F, and its relation to the RepA replicon of IncFII plasmids. J. Bacteriol. 169, 1836–1846 (1987).
Kawasaki, Y., Matsunaga, F., Kano, Y., Yura, T. & Wada, C. The localized melting of mini-F origin by the combined action of the mini-F initiator protein (RepE) and HU and DnaA of Escherichia coli. Mol. Gen. Genet. 253, 42–49 (1996).
Muraiso, K., Tokino, T., Murotsu, T. & Matsubara, K. Replication of mini-F plasmid in vitro promoted by purified E protein. Mol. Gen. Genet. 206, 519–521 (1987).
Ishiai, M., Wada, C., Kawasaki, Y. & Yura, T. Replication initiator protein RepE of mini-F plasmid: functional differentiation between monomers (initiator) and dimers (autogenous repressor). Proc. Natl Acad. Sci. USA 91, 3839–3843 (1994).
Manwaring, N. P., Skurray, R. A. & Firth, N. Nucleotide sequence of the F plasmid leading region. Plasmid 41, 219–225 (1999).
Lilly, J. & Camps, M. Mechanisms of theta plasmid replication. Microbiol. Spectr. 3, PLAS-0029-2014 (2015).
Lan, R., Alles, M. C., Donohoe, K., Martinez, M. B. & Reeves, P. R. Molecular evolutionary relationships of enteroinvasive Escherichia coli and Shigella spp. Infect. Immun. 72, 5080–5088 (2004).
Tinge, S. A. & Curtiss, R. Conservation of Salmonella typhimurium virulence plasmid maintenance regions among Salmonella serovars as a basis for plasmid curing. Infect. Immun. 58, 3084–3092 (1990).
Rodríguez-Peña, J. M., Buisan, M., Ibáñez, M. & Rotger, R. Genetic map of the virulence plasmid of Salmonella enteritidis and nucleotide sequence of its replicons. Gene 188, 53–61 (1997).
McNally, A., Thomson, N. R., Reuter, S. & Wren, B. W. ‘Add, stir and reduce’: Yersinia spp. as model bacteria for pathogen evolution. Nat. Rev. Microbiol. 14, 177–190 (2016).
Reuter, S. et al. Parallel independent evolution of pathogenicity within the genus Yersinia. Proc. Natl Acad. Sci. USA 111, 6768–6773 (2014).
Wang, H. et al. Increased plasmid copy number is essential for Yersinia T3SS function and virulence. Science 353, 492–495 (2016). This paper reveals that plasmid copy number and then virulence are shaped by host signals, such as the ambient temperature. The molecular mechanisms underlying this phenomenon are not known.
Ebersbach, G. & Gerdes, K. Plasmid segregation mechanisms. Annu. Rev. Genet. 39, 453–479 (2005).
Gerdes, K., Howard, M. & Szardenings, F. Pushing and pulling in prokaryotic DNA segregation. Cell 141, 927–942 (2010).
Brooks, A. C. & Hwang, L. C. Reconstitutions of plasmid partition systems and their mechanisms. Plasmid 91, 37–41 (2017).
Vecchiarelli, A. G., Mizuuchi, K. & Funnell, B. E. Surfing biological surfaces: exploiting the nucleoid for partition and transport in bacteria. Mol. Microbiol. 86, 513–523 (2012).
Vecchiarelli, A. G., Seol, Y., Neuman, K. C. & Mizuuchi, K. A moving ParA gradient on the nucleoid directs subcellular cargo transport via a chemophoresis force. Bioarchitecture 4, 154–159 (2014).
Møller-Jensen, J., Jensen, R. B., Löwe, J. & Gerdes, K. Prokaryotic DNA segregation by an actin-like filament. EMBO J. 21, 3119–3127 (2002).
Jensen, R. B. & Gerdes, K. Mechanism of DNA segregation in prokaryotes: ParM partitioning protein of plasmid R1 co-localizes with its replicon during the cell cycle. EMBO J. 18, 4076–4084 (1999).
Ebersbach, G. & Gerdes, K. The double par locus of virulence factor pB171: DNA segregation is correlated with oscillation of ParA. Proc. Natl Acad. Sci. USA 98, 15078–15083 (2001).
Ringgaard, S., Ebersbach, G., Borch, J. & Gerdes, K. Regulatory cross-talk in the double par locus of plasmid pB171. J. Biol. Chem. 282, 3134–3145 (2007). This paper reveals the regulation of the double partitioning locus of pB171 from EPEC E. coli B171.
Cerin, H. & Hackett, J. The parVP region of the Salmonella typhimurium virulence plasmid pSLT contains four loci required for incompatibility and partition. Plasmid 30, 30–38 (1993).
Chaudhuri, R. R. et al. Complete genome sequence and comparative metabolic profiling of the prototypical enteroaggregative Escherichia coli strain 042. PLoS ONE 5, e8801 (2010).
Brzozowska, I. & Zielenkiewicz, U. Regulation of toxin-antitoxin systems by proteolysis. Plasmid 70, 33–41 (2013).
Gerdes, K. & Maisonneuve, E. Bacterial persistence and toxin-antitoxin loci. Annu. Rev. Microbiol. 66, 103–123 (2012).
Harms, A., Brodersen, D. E., Mitarai, N. & Gerdes, K. Toxins, targets, and triggers: an overview of toxin-antitoxin biology. Mol. Cell. https://doi.org/10.1016/j.molcel.2018.01.003 (2018).
Dienemann, C., Bøggild, A., Winther, K. S., Gerdes, K. & Brodersen, D. E. Crystal structure of the VapBC toxin-antitoxin complex from Shigella flexneri reveals a hetero-octameric DNA-binding assembly. J. Mol. Biol. 414, 713–722 (2011). This work provides structural insights into the function of VapBC, the most common toxin–antitoxin system on virulence plasmids.
Winther, K. S. & Gerdes, K. Enteric virulence associated protein VapC inhibits translation by cleavage of initiator tRNA. Proc. Natl Acad. Sci. USA 108, 7403–7407 (2011).
McVicker, G. & Tang, C. M. Deletion of toxin-antitoxin systems in the evolution of Shigella sonnei as a host-adapted pathogen. Nat. Microbiol. 2, 16204 (2016).
Lobato-Márquez, D., Molina-García, L., Moreno-Córdoba, I., García-Del Portillo, F. & Díaz-Orejas, R. Stabilization of the virulence plasmid pSLT of Salmonella Typhimurium by three maintenance systems and its evaluation by using a new stability test. Front. Mol. Biosci. 3, 66 (2016).
Lobato-Márquez, D., Moreno-Córdoba, I., Figueroa, V., Díaz-Orejas, R. & García-del Portillo, F. Distinct type I and type II toxin-antitoxin modules control Salmonella lifestyle inside eukaryotic cells. Sci. Rep. 5, 9374 (2015). This paper reveals potential functions for plasmid toxin–antitoxin systems that are not concerned with plasmid maintenance.
Bernard, P. & Couturier, M. Cell killing by the F plasmid CcdB protein involves poisoning of DNA-topoisomerase II complexes. J. Mol. Biol. 226, 735–745 (1992).
Bahassi, E. M., Salmon, M. A., Van Melderen, L., Bernard, P. & Couturier, M. F plasmid CcdB killer protein: ccdB gene mutants coding for non-cytotoxic proteins which retain their regulatory functions. Mol. Microbiol. 15, 1031–1037 (1995).
Di Cesare, A. et al. Diverse distribution of toxin-antitoxin II systems in Salmonella enterica serovars. Sci. Rep. 6, 28759 (2016).
Christensen, S. K. & Gerdes, K. RelE toxins from bacteria and Archaea cleave mRNAs on translating ribosomes, which are rescued by tmRNA. Mol. Microbiol. 48, 1389–1400 (2003).
Pedersen, K. et al. The bacterial toxin RelE displays codon-specific cleavage of mRNAs in the ribosomal A site. Cell 112, 131–140 (2003).
Gerdes, K. et al. Mechanism of postsegregational killing by the hok gene product of the parB system of plasmid R1 and its homology with the relF gene product of the E. coli relB operon. EMBO J. 5, 2023–2029 (1986).
Loh, S. M., Cram, D. S. & Skurray, R. A. Nucleotide sequence and transcriptional analysis of a third function (Flm) involved in F-plasmid maintenance. Gene 66, 259–268 (1988).
Thisted, T. & Gerdes, K. Mechanism of post-segregational killing by the hok/sok system of plasmid R1. Sok antisense RNA regulates hok gene expression indirectly through the overlapping mok gene. J. Mol. Biol. 223, 41–54 (1992).
Thisted, T., Sorensen, N. S. & Gerdes, K. Mechanism of post-segregational killing: secondary structure analysis of the entire Hok mRNA from plasmid R1 suggests a fold-back structure that prevents translation and antisense RNA binding. J. Mol. Biol. 247, 859–873 (1995).
Jurenas, D. et al. AtaT blocks translation initiation by N-acetylation of the initiator tRNAfMet. Nat. Chem. Biol. 13, 640–646 (2017).
Cheverton, A. M. et al. A Salmonella toxin promotes persister formation through acetylation of tRNA. Mol. Cell 63, 86–96 (2016).
Jiang, Y., Pogliano, J., Helinski, D. R. & Konieczny, I. ParE toxin encoded by the broad-host-range plasmid RK2 is an inhibitor of Escherichia coli gyrase. Mol. Microbiol. 44, 971–979 (2002).
Gerdes, K. Toxin-antitoxin modules may regulate synthesis of macromolecules during nutritional stress. J. Bacteriol. 182, 561–572 (2000).
Kasari, V., Mets, T., Tenson, T. & Kaldalu, N. Transcriptional cross-activation between toxin-antitoxin systems of Escherichia coli. BMC Microbiol. 13, 45 (2013).
Wessner, F. et al. Regulatory crosstalk between type I and type II toxin-antitoxin systems in the human pathogen Enterococcus faecalis. RNA Biol. 12, 1099–1108 (2015).
Hyland, E. M., Wallace, E. W. & Murray, A. W. A model for the evolution of biological specificity: a cross-reacting DNA-binding protein causes plasmid incompatibility. J. Bacteriol. 196, 3002–3011 (2014).
Helaine, S. & Kugelberg, E. Bacterial persisters: formation, eradication, and experimental systems. Trends Microbiol. 22, 417–424 (2014).
Aviv, G. et al. A unique megaplasmid contributes to stress tolerance and pathogenicity of an emergent Salmonella enterica serovar Infantis strain. Environ. Microbiol. 16, 977–994 (2014).
Chen, C. L., Su, L. H., Janapatla, R. P., Lin, C. Y. & Chiu, C. H. Genetic analysis of virulence and antimicrobial-resistant plasmid pOU7519 in Salmonella enterica serovar Choleraesuis. J. Microbiol. Immunol. Infect. https://doi.org/10.1016/j.jmii.2017.11.004 (2017).
Barash, I. & Manulis-Sasson, S. Virulence mechanisms and host specificity of gall-forming Pantoea agglomerans. Trends Microbiol. 15, 538–545 (2007).
Koehler, T. M. Bacillus anthracis genetics and virulence gene regulation. Curr. Top. Microbiol. Immunol. 271, 143–164 (2002).
Watson, B., Currier, T. C., Gordon, M. P., Chilton, M. D. & Nester, E. W. Plasmid required for virulence of Agrobacterium tumefaciens. J. Bacteriol. 123, 255–264 (1975).
Franco, A. et al. Emergence of a clonal lineage of multidrug-resistant ESBL-producing Salmonella Infantis transmitted from broilers and broiler meat to humans in Italy between 2011 and 2014. PLoS ONE 10, e0144802 (2015).
Aviv, G., Rahav, G. & Gal-Mor, O. Horizontal transfer of the Salmonella enterica serovar Infantis resistance and virulence plasmid pESI to the gut microbiota of warm-blooded hosts. mBio 7, e01395–16 (2016).
Hammerl, J. A., Freytag, B., Lanka, E., Appel, B. & Hertwig, S. The pYV virulence plasmids of Yersinia pseudotuberculosis and Y. pestis contain a conserved DNA region responsible for the mobilization by the self-transmissible plasmid pYE854. Environ. Microbiol. Rep 4, 433–438 (2012).
Bikard, D. & Barrangou, R. Using CRISPR-Cas systems as antimicrobials. Curr. Opin. Microbiol. 37, 155–160 (2017).
Brenner, D. J. in The Prokaryotes (eds Balows, A., Truper, H. G., Dworkin, M., Harder, W. & Shleifer, K. H.) 2673–2695 (Springer, New York, 1992).
Eckburg, P. B. et al. Diversity of the human intestinal microbial flora. Science 308, 1635–1638 (2005).
Chow, J., Tang, H. & Mazmanian, S. K. Pathobionts of the gastrointestinal microbiota and inflammatory disease. Curr. Opin. Immunol. 23, 473–480 (2011).
Davin-Regli, A. & Pages, J. M. Enterobacter aerogenes and Enterobacter cloacae; versatile bacterial pathogens confronting antibiotic treatment. Front. Microbiol. 6, 392 (2015).
Zechner, E. L. Inflammatory disease caused by intestinal pathobionts. Curr. Opin. Microbiol. 35, 64–69 (2017).
Round, J. L. & Mazmanian, S. K. The gut microbiota shapes intestinal immune responses during health and disease. Nat. Rev. Immunol. 9, 313–323 (2009).
Radosavljevic, V., Finke, E. J. & Belojevic, G. Escherichia coli O104:H4 outbreak in Germany — clarification of the origin of the epidemic. Eur. J. Publ. Health 25, 125–129 (2015).
Pennington, T. H. E. coli O157 outbreaks in the United Kingdom: past, present, and future. Infect. Drug Resist 7, 211–222 (2014).
Heiman, K. E., Mody, R. K., Johnson, S. D., Griffin, P. M. & Gould, L. H. Escherichia coli O157 Outbreaks in the United States, 2003–2012. Emerg. Infect. Dis. 21, 1293–1301 (2015).
Yoder, J. S. et al. Outbreak of enterotoxigenic Escherichia coli infection with an unusually long duration of illness. Clin. Infect. Dis. 42, 1513–1517 (2006).
Croxen, M. A. et al. Recent advances in understanding enteric pathogenic Escherichia coli. Clin. Microbiol. Rev. 26, 822–880 (2013).
Pupo, G. M., Lan, R. & Reeves, P. R. Multiple independent origins of Shigella clones of Escherichia coli and convergent evolution of many of their characteristics. Proc. Natl Acad. Sci. USA 97, 10567–10572 (2000).
Lan, R. & Reeves, P. R. Escherichia coli in disguise: molecular origins of Shigella. Microbes Infect. 4, 1125–1132 (2002).
McClelland, M. et al. Complete genome sequence of Salmonella enterica serovar Typhimurium LT2. Nature 413, 852–856 (2001).
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.
Author information
Authors and Affiliations
Contributions
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.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
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.
Rights and permissions
About this article
Cite this article
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
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41579-018-0031-2
This article is cited by
-
Phage-plasmids promote recombination and emergence of phages and plasmids
Nature Communications (2024)
-
Multidrug-resistant Escherichia coli causing canine pyometra and urinary tract infections are genetically related but distinct from those causing prostatic abscesses
Scientific Reports (2024)
-
Towards a better understanding of antimicrobial resistance dissemination: what can be learnt from studying model conjugative plasmids?
Military Medical Research (2022)
-
Evaporation-induced hydrodynamics promote conjugation-mediated plasmid transfer in microbial populations
ISME Communications (2021)
-
Beyond horizontal gene transfer: the role of plasmids in bacterial evolution
Nature Reviews Microbiology (2021)