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Genomics of the Pathogenic Clostridia

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  • Authors: Robert J. Moore1,2, Jake A. Lacey3
  • Editors: Vincent A. Fischetti4, Richard P. Novick5, Joseph J. Ferretti6, Daniel A. Portnoy7, Miriam Braunstein8, Julian I. Rood9
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Host-Microbe Interactions Laboratory, School of Science, RMIT University, Bundoora, Victoria 3083, Australia; 2: Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia; 3: Doherty Department, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia; 4: The Rockefeller University, New York, NY; 5: Skirball Institute for Molecular Medicine, NYU Medical Center, New York, NY; 6: Department of Microbiology & Immunology, University of Oklahoma Health Science Center, Oklahoma City, OK; 7: Department of Molecular and Cellular Microbiology, University of California, Berkeley, Berkeley, CA; 8: Department of Microbiology and Immunology, University of North Carolina-Chapel Hill, Chapel Hill, NC; 9: Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia
  • Source: microbiolspec June 2019 vol. 7 no. 3 doi:10.1128/microbiolspec.GPP3-0033-2018
  • Received 13 May 2018 Accepted 10 October 2018 Published 21 June 2019
  • Robert J. Moore, [email protected]
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  • Abstract:

    Whole-genome sequences are now available for all the clinically important clostridia and many of the lesser or opportunistically pathogenic clostridia. The complex clade structures of , , and the species that produce botulinum toxins have been delineated by whole-genome sequence analysis. The true clostridia of cluster I show relatively low levels of gross genomic rearrangements within species, in contrast to the species of cluster XI, notably , which have been found to have very plastic genomes with significant levels of chromosomal rearrangement. Throughout the clostridial phylotypes, a large proportion of the strain diversity is driven by the acquisition and loss of mobile elements, including phages, plasmids, insertion sequences, and transposons. Genomic analysis has been used to investigate the diversity and spread of within hospital settings, the zoonotic transfer of isolates, and the emergence, origins, and geographic spread of epidemic ribotypes. In the clades defined by chromosomal sequence analysis show no indications of clustering based on host species or geographical location. Whole-genome sequence analysis helps to define the different survival and pathogenesis strategies that the clostridia use. Some, such as , produce toxins which rapidly act to kill the host, whereas others, such as and , produce less lethal toxins which can damage tissue but do not rapidly kill the host. The genomes provide a resource that can be mined to identify potential vaccine antigens and targets for other forms of therapeutic intervention.

  • Citation: Moore R, Lacey J. 2019. Genomics of the Pathogenic Clostridia. Microbiol Spectrum 7(3):GPP3-0033-2018. doi:10.1128/microbiolspec.GPP3-0033-2018.

References

1. Lee WH, Riemann H. 1970. Correlation of toxic and non-toxic strains of Clostridium botulinum by DNA composition and homology. J Gen Microbiol 60:117–123 http://dx.doi.org/10.1099/00221287-60-1-117. [PubMed]
2. Hill LR. 1966. An index to deoxyribonucleic acid base compositions of bacterial species. J Gen Microbiol 44:419–437 http://dx.doi.org/10.1099/00221287-44-3-419. [PubMed]
3. Schildkraut CL, Marmur J, Doty P. 1962. Determination of the base composition of deoxyribonucleic acid from its buoyant density in CsCl. J Mol Biol 4:430–443 http://dx.doi.org/10.1016/S0022-2836(62)80100-4.
4. Kristjánsson M, Samore MH, Gerding DN, DeGirolami PC, Bettin KM, Karchmer AW, Arbeit RD. 1994. Comparison of restriction endonuclease analysis, ribotyping, and pulsed-field gel electrophoresis for molecular differentiation of Clostridium difficile strains. J Clin Microbiol 32:1963–1969.
5. Suen G, Goldman BS, Welch RD. 2007. Predicting prokaryotic ecological niches using genome sequence analysis. PLoS One 2:e743 http://dx.doi.org/10.1371/journal.pone.0000743. [PubMed]
6. Lawson PA, Rainey FA. 2016. Proposal to restrict the genus Clostridium Prazmowski to Clostridium butyricum and related species. Int J Syst Evol Microbiol 66:1009–1016 http://dx.doi.org/10.1099/ijsem.0.000824. [PubMed]
7. Parks DH, Chuvochina M, Waite DW, Rinke C, Skarshewski A, Chaumeil P-A, Hugenholtz P. 2018. A standardized bacterial taxonomy based on genome phylogeny substantially revises the tree of life. Nat Biotechnol http://dx.doi.org/10.1038/nbt.4229.
8. Collins MD, Lawson PA, Willems A, Cordoba JJ, Fernandez-Garayzabal J, Garcia P, Cai J, Hippe H, Farrow JAE. 1994. The phylogeny of the genus Clostridium: proposal of five new genera and eleven new species combinations. Int J Syst Bacteriol 44:812–826 http://dx.doi.org/10.1099/00207713-44-4-812. [PubMed]
9. Ezaki T. 2009. Family VII. Peptostreptococcaceae fam. nov. p 1008–1009. In: DeVos P, Garrity GM, Jones D, Krieg NR, Ludwig W, Rainey FA, Schleifer K-H, Whitman WB (eds), Bergey’s Manual of Systematic Bacteriology, Vol 3, 2nd ed. Springer, New York, NY.
10. Gerritsen J, Fuentes S, Grievink W, van Niftrik L, Tindall BJ, Timmerman HM, Rijkers GT, Smidt H. 2014. Characterization of Romboutsia ilealis gen. nov., sp. nov., isolated from the gastro-intestinal tract of a rat, and proposal for the reclassification of five closely related members of the genus Clostridium into the genera Romboutsia gen. nov., Intestinibacter gen. nov., Terrisporobacter gen. nov. and Asaccharospora gen. nov. Int J Syst Evol Microbiol 64:1600–1616 http://dx.doi.org/10.1099/ijs.0.059543-0. [PubMed]
11. Sasi Jyothsna TS, Tushar L, Sasikala C, Ramana CV. 2016. Paraclostridium benzoelyticum gen. nov., sp. nov., isolated from marine sediment and reclassification of Clostridium bifermentans as Paraclostridium bifermentans comb. nov. Proposal of a new genus Paeniclostridium gen. nov. to accommodate Clostridium sordellii and Clostridium ghonii. Int J Syst Evol Microbiol 66:1268–1274 http://dx.doi.org/10.1099/ijsem.0.000874. [PubMed]
12. Lawson PA, Citron DM, Tyrrell KL, Finegold SM. 2016. Reclassification of Clostridium difficile as Clostridioides difficile (Hall and O’Toole 1935) Prévot 1938. Anaerobe 40:95–99 http://dx.doi.org/10.1016/j.anaerobe.2016.06.008. [PubMed]
13. Oren A, Garrity GM. 2016. List of new names and new combinations previously effectively, but not validly, published. Int J Syst Evol Microbiol 66:3761–3764 http://dx.doi.org/10.1099/ijsem.0.000919. [PubMed]
14. Collins MD, East AK. 1998. Phylogeny and taxonomy of the food-borne pathogen Clostridium botulinum and its neurotoxins. J Appl Microbiol 84:5–17 http://dx.doi.org/10.1046/j.1365-2672.1997.00313.x. [PubMed]
15. Smith TJ, Lou J, Geren IN, Forsyth CM, Tsai R, Laporte SL, Tepp WH, Bradshaw M, Johnson EA, Smith LA, Marks JD. 2005. Sequence variation within botulinum neurotoxin serotypes impacts antibody binding and neutralization. Infect Immun 73:5450–5457 http://dx.doi.org/10.1128/IAI.73.9.5450-5457.2005. [PubMed]
16. Hill KK, Smith TJ. 2013. Genetic diversity within Clostridium botulinum serotypes, botulinum neurotoxin gene clusters and toxin subtypes. Curr Top Microbiol Immunol 364:1–20. [PubMed]
17. Maslanka SE, Lúquez C, Dykes JK, Tepp WH, Pier CL, Pellett S, Raphael BH, Kalb SR, Barr JR, Rao A, Johnson EA. 2016. A novel botulinum neurotoxin, previously reported as serotype H, has a hybrid-like structure with regions of similarity to the structures of serotypes A and F and is neutralized with serotype A antitoxin. J Infect Dis 213:379–385 http://dx.doi.org/10.1093/infdis/jiv327. [PubMed]
18. Zhang S, Masuyer G, Zhang J, Shen Y, Lundin D, Henriksson L, Miyashita S-I, Martínez-Carranza M, Dong M, Stenmark P. 2017. Identification and characterization of a novel botulinum neurotoxin. Nat Commun 8:14130 http://dx.doi.org/10.1038/ncomms14130. [PubMed]
19. Raffestin S, Marvaud JC, Cerrato R, Dupuy B, Popoff MR. 2004. Organization and regulation of the neurotoxin genes in Clostridium botulinum and Clostridium tetani. Anaerobe 10:93–100 http://dx.doi.org/10.1016/j.anaerobe.2004.01.001. [PubMed]
20. Williamson CHD, Sahl JW, Smith TJ, Xie G, Foley BT, Smith LA, Fernández RA, Lindström M, Korkeala H, Keim P, Foster J, Hill K. 2016. Comparative genomic analyses reveal broad diversity in botulinum-toxin-producing clostridia. BMC Genomics 17:180 http://dx.doi.org/10.1186/s12864-016-2502-z. [PubMed]
21. Smith TJ, Hill KK, Raphael BH. 2015. Historical and current perspectives on Clostridium botulinum diversity. Res Microbiol 166:290–302 http://dx.doi.org/10.1016/j.resmic.2014.09.007. [PubMed]
22. Nawrocki EM, Bradshaw M, Johnson EA. 2018. Botulinum neurotoxin-encoding plasmids can be conjugatively transferred to diverse clostridial strains. Sci Rep 8:3100 http://dx.doi.org/10.1038/s41598-018-21342-9. [PubMed]
23. Oguma K. 1976. The stability of toxigenicity in Clostridium botulinum types C and D. J Gen Microbiol 92:67–75 http://dx.doi.org/10.1099/00221287-92-1-67. [PubMed]
24. Sakaguchi Y, Hayashi T, Kurokawa K, Nakayama K, Oshima K, Fujinaga Y, Ohnishi M, Ohtsubo E, Hattori M, Oguma K. 2005. The genome sequence of Clostridium botulinum type C neurotoxin-converting phage and the molecular mechanisms of unstable lysogeny. Proc Natl Acad Sci U S A 102:17472–17477 http://dx.doi.org/10.1073/pnas.0505503102. [PubMed]
25. Brunt J, van Vliet AHM, van den Bos F, Carter AT, Peck MW. 2016. Diversity of the germination apparatus in Clostridium botulinum groups I, II, III, and IV. Front Microbiol 7:1702 http://dx.doi.org/10.3389/fmicb.2016.01702. [PubMed]
26. Brüggemann H, Gottschalk G. 2004. Insights in metabolism and toxin production from the complete genome sequence of Clostridium tetani. Anaerobe 10:53–68 http://dx.doi.org/10.1016/j.anaerobe.2003.08.001. [PubMed]
27. Schiavo G, Rossetto O, Benfenati F, Poulain B, Montecucco C. 1994. Tetanus and botulinum neurotoxins are zinc proteases specific for components of the neuroexocytosis apparatus. Ann N Y Acad Sci 710(1 Toxins and Ex) :65–75 http://dx.doi.org/10.1111/j.1749-6632.1994.tb26614.x. [PubMed]
28. Afshar M, Raju M, Ansell D, Bleck TP. 2011. Narrative review: tetanus—a health threat after natural disasters in developing countries. Ann Intern Med 154:329–335 http://dx.doi.org/10.7326/0003-4819-154-5-201103010-00007. [PubMed]
29. Cohen JE, Wang R, Shen R-F, Wu WW, Keller JE. 2017. Comparative pathogenomics of Clostridium tetani. PLoS One 12:e0182909 http://dx.doi.org/10.1371/journal.pone.0182909. [PubMed]
30. Brüggemann H, Brzuszkiewicz E, Chapeton-Montes D, Plourde L, Speck D, Popoff MR. 2015. Genomics of Clostridium tetani. Res Microbiol 166:326–331 http://dx.doi.org/10.1016/j.resmic.2015.01.002. [PubMed]
31. Skarin H, Håfström T, Westerberg J, Segerman B. 2011. Clostridium botulinum group III: a group with dual identity shaped by plasmids, phages and mobile elements. BMC Genomics 12:185 http://dx.doi.org/10.1186/1471-2164-12-185. [PubMed]
32. Sasaki Y, Takikawa N, Kojima A, Norimatsu M, Suzuki S, Tamura Y. 2001. Phylogenetic positions of Clostridium novyi and Clostridium haemolyticum based on 16S rDNA sequences. Int J Syst Evol Microbiol 51:901–904 http://dx.doi.org/10.1099/00207713-51-3-901. [PubMed]
33. Skarin H, Segerman B. 2014. Plasmidome interchange between Clostridium botulinum, Clostridium novyi and Clostridium haemolyticum converts strains of independent lineages into distinctly different pathogens. PLoS One 9:e107777 http://dx.doi.org/10.1371/journal.pone.0107777. [PubMed]
34. Uzal FA, Freedman JC, Shrestha A, Theoret JR, Garcia J, Awad MM, Adams V, Moore RJ, Rood JI, McClane BA. 2014. Towards an understanding of the role of Clostridium perfringens toxins in human and animal disease. Future Microbiol 9:361–377 http://dx.doi.org/10.2217/fmb.13.168. [PubMed]
35. Rood JI, Adams V, Lacey J, Lyras D, McClane BA, Melville SB, Moore RJ, Popoff MR, Sarker MR, Songer JG, Uzal FA, Van Immerseel F. 2018. Expansion of the Clostridium perfringens toxin-based typing scheme. Anaerobe. Epub ahead of print. doi:10.1016/j.anaerobe.2018.04.011. [PubMed]
36. Lacey JA, Allnutt TR, Vezina B, Van TTH, Stent T, Han X, Rood JI, Wade B, Keyburn AL, Seemann T, Chen H, Haring V, Johanesen PA, Lyras D, Moore RJ. 2018. Whole genome analysis reveals the diversity and evolutionary relationships between necrotic enteritis-causing strains of Clostridium perfringens. BMC Genomics 19:379 http://dx.doi.org/10.1186/s12864-018-4771-1. [PubMed]
37. Lacey JA, Keyburn AL, Ford ME, Portela RW, Johanesen PA, Lyras D, Moore RJ. 2017. Conjugation-mediated horizontal gene transfer of Clostridium perfringens plasmids in the chicken gastrointestinal tract results in the formation of new virulent strains. Appl Environ Microbiol 83:e01814-17 http://dx.doi.org/10.1128/AEM.01814-17. [PubMed]
38. Bannam TL, Yan X-X, Harrison PF, Seemann T, Keyburn AL, Stubenrauch C, Weeramantri LH, Cheung JK, McClane BA, Boyce JD, Moore RJ, Rood JI. 2011. Necrotic enteritis-derived Clostridium perfringens strain with three closely related independently conjugative toxin and antibiotic resistance plasmids. MBio 2:e00190-11 http://dx.doi.org/10.1128/mBio.00190-11. [PubMed]
39. Lepp D, Roxas B, Parreira VR, Marri PR, Rosey EL, Gong J, Songer JG, Vedantam G, Prescott JF. 2010. Identification of novel pathogenicity loci in Clostridium perfringens strains that cause avian necrotic enteritis. PLoS One 5:e10795 http://dx.doi.org/10.1371/journal.pone.0010795. [PubMed]
40. Ronco T, Stegger M, Ng KL, Lilje B, Lyhs U, Andersen PS, Pedersen K. 2017. Genome analysis of Clostridium perfringens isolates from healthy and necrotic enteritis infected chickens and turkeys. BMC Res Notes 10:270 http://dx.doi.org/10.1186/s13104-017-2594-9. [PubMed]
41. Lacey JA, Johanesen PA, Lyras D, Moore RJ. 2016. Genomic diversity of necrotic enteritis-associated strains of Clostridium perfringens: a review. Avian Pathol 45:302–307 http://dx.doi.org/10.1080/03079457.2016.1153799. [PubMed]
42. Lepp D, Gong J, Songer JG, Boerlin P, Parreira VR, Prescott JF. 2013. Identification of accessory genome regions in poultry Clostridium perfringens isolates carrying the netB plasmid. J Bacteriol 195:1152–1166 http://dx.doi.org/10.1128/JB.01032-12. [PubMed]
43. Hassan KA, Elbourne LDH, Tetu SG, Melville SB, Rood JI, Paulsen IT. 2015. Genomic analyses of Clostridium perfringens isolates from five toxinotypes. Res Microbiol 166:255–263 http://dx.doi.org/10.1016/j.resmic.2014.10.003. [PubMed]
44. Myers GSA, Rasko DA, Cheung JK, Ravel J, Seshadri R, DeBoy RT, Ren Q, Varga J, Awad MM, Brinkac LM, Daugherty SC, Haft DH, Dodson RJ, Madupu R, Nelson WC, Rosovitz MJ, Sullivan SA, Khouri H, Dimitrov GI, Watkins KL, Mulligan S, Benton J, Radune D, Fisher DJ, Atkins HS, Hiscox T, Jost BH, Billington SJ, Songer JG, McClane BA, Titball RW, Rood JI, Melville SB, Paulsen IT. 2006. Skewed genomic variability in strains of the toxigenic bacterial pathogen, Clostridium perfringens. Genome Res 16:1031–1040 http://dx.doi.org/10.1101/gr.5238106. [PubMed]
45. Eyre DW, Cule ML, Wilson DJ, Griffiths D, Vaughan A, O’Connor L, Ip CLC, Golubchik T, Batty EM, Finney JM, Wyllie DH, Didelot X, Piazza P, Bowden R, Dingle KE, Harding RM, Crook DW, Wilcox MH, Peto TEA, Walker AS. 2013. Diverse sources of C. difficile infection identified on whole-genome sequencing. N Engl J Med 369:1195–1205 http://dx.doi.org/10.1056/NEJMoa1216064. [PubMed]
46. Janezic S, Rupnik M. 2015. Genomic diversity of Clostridium difficile strains. Res Microbiol 166:353–360 http://dx.doi.org/10.1016/j.resmic.2015.02.002. [PubMed]
47. Knight DR, Elliott B, Chang BJ, Perkins TT, Riley TV. 2015. Diversity and evolution in the genome of Clostridium difficile. Clin Microbiol Rev 28:721–741 http://dx.doi.org/10.1128/CMR.00127-14. [PubMed]
48. Lemee L, Dhalluin A, Pestel-Caron M, Lemeland J-F, Pons J-L. 2004. Multilocus sequence typing analysis of human and animal Clostridium difficile isolates of various toxigenic types. J Clin Microbiol 42:2609–2617 http://dx.doi.org/10.1128/JCM.42.6.2609-2617.2004. [PubMed]
49. Griffiths D, Fawley W, Kachrimanidou M, Bowden R, Crook DW, Fung R, Golubchik T, Harding RM, Jeffery KJM, Jolley KA, Kirton R, Peto TE, Rees G, Stoesser N, Vaughan A, Walker AS, Young BC, Wilcox M, Dingle KE. 2010. Multilocus sequence typing of Clostridium difficile. J Clin Microbiol 48:770–778 http://dx.doi.org/10.1128/JCM.01796-09. [PubMed]
50. Knetsch CW, Terveer EM, Lauber C, Gorbalenya AE, Harmanus C, Kuijper EJ, Corver J, van Leeuwen HC. 2012. Comparative analysis of an expanded Clostridium difficile reference strain collection reveals genetic diversity and evolution through six lineages. Infect Genet Evol 12:1577–1585 http://dx.doi.org/10.1016/j.meegid.2012.06.003. [PubMed]
51. He M, Sebaihia M, Lawley TD, Stabler RA, Dawson LF, Martin MJ, Holt KE, Seth-Smith HMB, Quail MA, Rance R, Brooks K, Churcher C, Harris D, Bentley SD, Burrows C, Clark L, Corton C, Murray V, Rose G, Thurston S, van Tonder A, Walker D, Wren BW, Dougan G, Parkhill J. 2010. Evolutionary dynamics of Clostridium difficile over short and long time scales. Proc Natl Acad Sci U S A 107:7527–7532 http://dx.doi.org/10.1073/pnas.0914322107. [PubMed]
52. Dingle KE, Elliott B, Robinson E, Griffiths D, Eyre DW, Stoesser N, Vaughan A, Golubchik T, Fawley WN, Wilcox MH, Peto TE, Walker AS, Riley TV, Crook DW, Didelot X. 2014. Evolutionary history of the Clostridium difficile pathogenicity locus. Genome Biol Evol 6:36–52 http://dx.doi.org/10.1093/gbe/evt204. [PubMed]
53. Janezic S, Potocnik M, Zidaric V, Rupnik M. 2016. Highly divergent Clostridium difficile strains isolated from the environment. PLoS One 11:e0167101 http://dx.doi.org/10.1371/journal.pone.0167101. [PubMed]
54. Scaria J, Ponnala L, Janvilisri T, Yan W, Mueller LA, Chang Y-F. 2010. Analysis of ultra low genome conservation in Clostridium difficile. PLoS One 5:e15147 http://dx.doi.org/10.1371/journal.pone.0015147. [PubMed]
55. Forgetta V, Oughton MT, Marquis P, Brukner I, Blanchette R, Haub K, Magrini V, Mardis ER, Gerding DN, Loo VG, Miller MA, Mulvey MR, Rupnik M, Dascal A, Dewar K. 2011. Fourteen-genome comparison identifies DNA markers for severe-disease-associated strains of Clostridium difficile. J Clin Microbiol 49:2230–2238 http://dx.doi.org/10.1128/JCM.00391-11. [PubMed]
56. Scaria J, Mao C, Chen J-W, McDonough SP, Sobral B, Chang Y-F. 2013. Differential stress transcriptome landscape of historic and recently emerged hypervirulent strains of Clostridium difficile strains determined using RNA-seq. PLoS One 8:e78489 http://dx.doi.org/10.1371/journal.pone.0078489. [PubMed]
57. Stabler RA, He M, Dawson L, Martin M, Valiente E, Corton C, Lawley TD, Sebaihia M, Quail MA, Rose G, Gerding DN, Gibert M, Popoff MR, Parkhill J, Dougan G, Wren BW. 2009. Comparative genome and phenotypic analysis of Clostridium difficile 027 strains provides insight into the evolution of a hypervirulent bacterium. Genome Biol 10:R102 http://dx.doi.org/10.1186/gb-2009-10-9-r102. [PubMed]
58. Murillo T, Ramírez-Vargas G, Riedel T, Overmann J, Andersen JM, Guzmán-Verri C, Chaves-Olarte E, Rodríguez C, Dagan T. 2018. Two groups of cocirculating, epidemic Clostridiodes difficile strains microdiversify through different mechanisms. Genome Biol Evol 10:982–998 http://dx.doi.org/10.1093/gbe/evy059. [PubMed]
59. He M, Miyajima F, Roberts P, Ellison L, Pickard DJ, Martin MJ, Connor TR, Harris SR, Fairley D, Bamford KB, D’Arc S, Brazier J, Brown D, Coia JE, Douce G, Gerding D, Kim HJ, Koh TH, Kato H, Senoh M, Louie T, Michell S, Butt E, Peacock SJ, Brown NM, Riley T, Songer G, Wilcox M, Pirmohamed M, Kuijper E, Hawkey P, Wren BW, Dougan G, Parkhill J, Lawley TD. 2013. Emergence and global spread of epidemic healthcare-associated Clostridium difficile. Nat Genet 45:109–113 http://dx.doi.org/10.1038/ng.2478. [PubMed]
60. Collins J, Robinson C, Danhof H, Knetsch CW, van Leeuwen HC, Lawley TD, Auchtung JM, Britton RA. 2018. Dietary trehalose enhances virulence of epidemic Clostridium difficile. Nature 553:291–294 http://dx.doi.org/10.1038/nature25178. [PubMed]
61. Cairns MD, Preston MD, Hall CL, Gerding DN, Hawkey PM, Kato H, Kim H, Kuijper EJ, Lawley TD, Pituch H, Reid S, Kullin B, Riley TV, Solomon K, Tsai PJ, Weese JS, Stabler RA, Wren BW. 2017. Comparative genome analysis and global phylogeny of the toxin variant Clostridium difficile PCR ribotype 017 reveals the evolution of two independent sublineages. J Clin Microbiol 55:865–876 http://dx.doi.org/10.1128/JCM.01296-16. [PubMed]
62. Collins DA, Hawkey PM, Riley TV. 2013. Epidemiology of Clostridium difficile infection in Asia. Antimicrob Resist Infect Control 2:21 http://dx.doi.org/10.1186/2047-2994-2-21. [PubMed]
63. Sebaihia M, Wren BW, Mullany P, Fairweather NF, Minton N, Stabler R, Thomson NR, Roberts AP, Cerdeño-Tárraga AM, Wang H, Holden MTG, Wright A, Churcher C, Quail MA, Baker S, Bason N, Brooks K, Chillingworth T, Cronin A, Davis P, Dowd L, Fraser A, Feltwell T, Hance Z, Holroyd S, Jagels K, Moule S, Mungall K, Price C, Rabbinowitsch E, Sharp S, Simmonds M, Stevens K, Unwin L, Whithead S, Dupuy B, Dougan G, Barrell B, Parkhill J. 2006. The multidrug-resistant human pathogen Clostridium difficile has a highly mobile, mosaic genome. Nat Genet 38:779–786 http://dx.doi.org/10.1038/ng1830. [PubMed]
64. Stabler RA, Valiente E, Dawson LF, He M, Parkhill J, Wren BW. 2010. In-depth genetic analysis of Clostridium difficile PCR-ribotype 027 strains reveals high genome fluidity including point mutations and inversions. Gut Microbes 1:269–276 http://dx.doi.org/10.4161/gmic.1.4.11870. [PubMed]
65. Smits WK, Weese JS, Roberts AP, Harmanus C, Hornung B. 2018. A helicase-containing module defines a family of pCD630-like plasmids in Clostridium difficile. Anaerobe 49:78–84 http://dx.doi.org/10.1016/j.anaerobe.2017.12.005. [PubMed]
66. Johanesen P, Lyras D. 2016. Methods for determining transfer of mobile genetic elements in Clostridium difficile. Methods Mol Biol 1476:199–2134. [PubMed]
67. Govind R, Vediyappan G, Rolfe RD, Dupuy B, Fralick JA. 2009. Bacteriophage-mediated toxin gene regulation in Clostridium difficile. J Virol 83:12037–12045 http://dx.doi.org/10.1128/JVI.01256-09. [PubMed]
68. Hargreaves KR, Kropinski AM, Clokie MRJ. 2014. What does the talking? Quorum sensing signalling genes discovered in a bacteriophage genome. PLoS One 9:e85131 http://dx.doi.org/10.1371/journal.pone.0085131. [PubMed]
69. Goh S, Ong PF, Song KP, Riley TV, Chang BJ. 2007. The complete genome sequence of Clostridium difficile phage phiC2 and comparisons to phiCD119 and inducible prophages of CD630. Microbiology 153:676–685 http://dx.doi.org/10.1099/mic.0.2006/002436-0. [PubMed]
70. Rupnik M, Dupuy B, Fairweather NF, Gerding DN, Johnson S, Just I, Lyerly DM, Popoff MR, Rood JI, Sonenshein AL, Thelestam M, Wren BW, Wilkins TD, von Eichel-Streiber C. 2005. Revised nomenclature of Clostridium difficile toxins and associated genes. J Med Microbiol 54:113–117 http://dx.doi.org/10.1099/jmm.0.45810-0. [PubMed]
71. Monot M, Boursaux-Eude C, Thibonnier M, Vallenet D, Moszer I, Medigue C, Martin-Verstraete I, Dupuy B. 2011. Reannotation of the genome sequence of Clostridium difficile strain 630. J Med Microbiol 60:1193–1199 http://dx.doi.org/10.1099/jmm.0.030452-0. [PubMed]
72. Braun V, Hundsberger T, Leukel P, Sauerborn M, von Eichel-Streiber C. 1996. Definition of the single integration site of the pathogenicity locus in Clostridium difficile. Gene 181:29–38 http://dx.doi.org/10.1016/S0378-1119(96)00398-8.
73. Kim SJ, Kim H, Seo Y, Yong D, Jeong SH, Chong Y, Lee K. 2010. Molecular characterization of toxin A-negative, toxin B-positive variant strains of Clostridium difficile isolated in Korea. Diagn Microbiol Infect Dis 67:198–201 http://dx.doi.org/10.1016/j.diagmicrobio.2010.01.007. [PubMed]
74. Didelot X, Eyre DW, Cule M, Ip CL, Ansari MA, Griffiths D, Vaughan A, O’Connor L, Golubchik T, Batty EM, Piazza P, Wilson DJ, Bowden R, Donnelly PJ, Dingle KE, Wilcox M, Walker AS, Crook DW, Peto TE, Harding RM. 2012. Microevolutionary analysis of Clostridium difficile genomes to investigate transmission. Genome Biol 13:R118 http://dx.doi.org/10.1186/gb-2012-13-12-r118. [PubMed]
75. Kumar N, Miyajima F, He M, Roberts P, Swale A, Ellison L, Pickard D, Smith G, Molyneux R, Dougan G, Parkhill J, Wren BW, Parry CM, Pirmohamed M, Lawley TD. 2016. Genome-based infection tracking reveals dynamics of Clostridium difficile transmission and disease recurrence. Clin Infect Dis 62:746–752 http://dx.doi.org/10.1093/cid/civ1031. [PubMed]
76. Eyre DW, Griffiths D, Vaughan A, Golubchik T, Acharya M, O’Connor L, Crook DW, Walker AS, Peto TEA. 2013. Asymptomatic Clostridium difficile colonisation and onward transmission. PLoS One 8:e78445 http://dx.doi.org/10.1371/journal.pone.0078445. [PubMed]
77. Knetsch CW, Connor TR, Mutreja A, van Dorp SM, Sanders IM, Browne HP, Harris D, Lipman L, Keessen EC, Corver J, Kuijper EJ, Lawley TD. 2014. Whole genome sequencing reveals potential spread of Clostridium difficile between humans and farm animals in the Netherlands, 2002 to 2011. Euro Surveill 19:20954 http://dx.doi.org/10.2807/1560-7917.ES2014.19.45.20954. [PubMed]
78. Knight DR, Squire MM, Collins DA, Riley TV. 2017. Genome analysis of Clostridium difficile PCR ribotype 014 lineage in Australian pigs and humans reveals a diverse genetic repertoire and signatures of long-range interspecies transmission. Front Microbiol 7:2138 http://dx.doi.org/10.3389/fmicb.2016.02138. [PubMed]
79. Groß U, Brzuszkiewicz E, Gunka K, Starke J, Riedel T, Bunk B, Spröer C, Wetzel D, Poehlein A, Chibani C, Bohne W, Overmann J, Zimmermann O, Daniel R, Liesegang H. 2018. Comparative genome and phenotypic analysis of three Clostridioides difficile strains isolated from a single patient provide insight into multiple infection of C. difficile. BMC Genomics 19:1 http://dx.doi.org/10.1186/s12864-017-4368-0. [PubMed]
80. Sachsenheimer FE, Yang I, Zimmermann O, Wrede C, Müller LV, Gunka K, Groß U, Suerbaum S. 2018. Genomic and phenotypic diversity of Clostridium difficile during long-term sequential recurrences of infection. Int J Med Microbiol 308:364–377 http://dx.doi.org/10.1016/j.ijmm.2018.02.002. [PubMed]
81. Eyre DW, Babakhani F, Griffiths D, Seddon J, Del Ojo Elias C, Gorbach SL, Peto TEA, Crook DW, Walker AS. 2014. Whole-genome sequencing demonstrates that fidaxomicin is superior to vancomycin for preventing reinfection and relapse of infection with Clostridium difficile. J Infect Dis 209:1446–1451 http://dx.doi.org/10.1093/infdis/jit598. [PubMed]
82. Couchman EC, Browne HP, Dunn M, Lawley TD, Songer JG, Hall V, Petrovska L, Vidor C, Awad M, Lyras D, Fairweather NF. 2015. Clostridium sordellii genome analysis reveals plasmid localized toxin genes encoded within pathogenicity loci. BMC Genomics 16:392 http://dx.doi.org/10.1186/s12864-015-1613-2. [PubMed]
83. Scaria J, Suzuki H, Ptak CP, Chen J-W, Zhu Y, Guo X-K, Chang Y-F. 2015. Comparative genomic and phenomic analysis of Clostridium difficile and Clostridium sordellii, two related pathogens with differing host tissue preference. BMC Genomics 16:448 http://dx.doi.org/10.1186/s12864-015-1663-5. [PubMed]
84. Vidor C, Awad M, Lyras D. 2015. Antibiotic resistance, virulence factors and genetics of Clostridium sordellii. Res Microbiol 166:368–374 http://dx.doi.org/10.1016/j.resmic.2014.09.003. [PubMed]
85. Keyburn AL, Yan X-X, Bannam TL, Van Immerseel F, Rood JI, Moore RJ. 2010. Association between avian necrotic enteritis and Clostridium perfringens strains expressing NetB toxin. Vet Res 41:21 http://dx.doi.org/10.1051/vetres/2009069. [PubMed]
86. Vidor CJ, Watts TD, Adams V, Bulach D, Couchman E, Rood JI, Fairweather NF, Awad M, Lyras D. 2018. Clostridium sordellii pathogenicity locus plasmid pCS1-1 encodes a novel clostridial conjugation locus. MBio 9:e01761-17 http://dx.doi.org/10.1128/mBio.01761-17. [PubMed]
87. Dehoux P, Marvaud JC, Abouelleil A, Earl AM, Lambert T, Dauga C. 2016. Comparative genomics of Clostridium bolteae and Clostridium clostridioforme reveals species-specific genomic properties and numerous putative antibiotic resistance determinants. BMC Genomics 17:819 http://dx.doi.org/10.1186/s12864-016-3152-x. [PubMed]
88. Useh NM, Nok AJ, Esievo KA. 2003. Pathogenesis and pathology of blackleg in ruminants: the role of toxins and neuraminidase. A short review. Vet Q 25:155–159 http://dx.doi.org/10.1080/01652176.2003.9695158. [PubMed]
89. Uzal FA. 2012. Evidence-based medicine concerning efficacy of vaccination against Clostridium chauvoei infection in cattle. Vet Clin North Am Food Anim Pract 28:71–77, viii http://dx.doi.org/10.1016/j.cvfa.2011.12.006. [PubMed]
90. Weatherhead JE, Tweardy DJ. 2012. Lethal human neutropenic entercolitis caused by Clostridium chauvoei in the United States: tip of the iceberg? J Infect 64:225–227 http://dx.doi.org/10.1016/j.jinf.2011.09.004. [PubMed]
91. Frey J, Falquet L. 2015. Patho-genetics of Clostridium chauvoei. Res Microbiol 166:384–392 http://dx.doi.org/10.1016/j.resmic.2014.10.013. [PubMed]
92. Thomas P, Semmler T, Eichhorn I, Lübke-Becker A, Werckenthin C, Abdel-Glil MY, Wieler LH, Neubauer H, Seyboldt C. 2017. First report of two complete Clostridium chauvoei genome sequences and detailed in silico genome analysis. Infect Genet Evol 54:287–298 http://dx.doi.org/10.1016/j.meegid.2017.07.018. [PubMed]
93. Rychener L, InAlbon S, Djordjevic SP, Chowdhury PR, Ziech RE, de Vargas AC, Frey J, Falquet L. 2017. Clostridium chauvoei, an evolutionary dead-end pathogen. Front Microbiol 8:1054 http://dx.doi.org/10.3389/fmicb.2017.01054. [PubMed]
94. Srivastava I, Aldape MJ, Bryant AE, Stevens DL. 2017. Spontaneous C. septicum gas gangrene: a literature review. Anaerobe 48:165–171 http://dx.doi.org/10.1016/j.anaerobe.2017.07.008. [PubMed]
95. Stevens DL, Aldape MJ, Bryant AE. 2012. Life-threatening clostridial infections. Anaerobe 18:254–259 http://dx.doi.org/10.1016/j.anaerobe.2011.11.001. [PubMed]
96. Benamar S, Cassir N, Caputo A, Cadoret F, La Scola B. 2016. Complete genome sequence of Clostridium septicum strain CSUR P1044, isolated from the human gut microbiota. Genome Announc 4:e00922-16 http://dx.doi.org/10.1128/genomeA.00922-16. [PubMed]
97. Stoddard SF, Smith BJ, Hein R, Roller BRK, Schmidt TM. 2015. rrnDB: improved tools for interpreting rRNA gene abundance in bacteria and archaea and a new foundation for future development. Nucleic Acids Res 43(D1) :D593–D598 http://dx.doi.org/10.1093/nar/gku1201. [PubMed]
98. Kiu R, Caim S, Alcon-Giner C, Belteki G, Clarke P, Pickard D, Dougan G, Hall LJ. 2017. Preterm infant-associated Clostridium tertium, Clostridium cadaveris, and Clostridium paraputrificum strains: genomic and evolutionary insights. Genome Biol Evol 9:2707–2714 http://dx.doi.org/10.1093/gbe/evx210. [PubMed]
99. Wong YM, Juan JC, Gan HM, Austin CM. 2014. Draft genome sequence of Clostridium bifermentans strain WYM, a promising biohydrogen producer isolated from landfill leachate sludge. Genome Announc 2:e00077-14. [PubMed]
100. Zhou C, Ma Q, Mao X, Liu B, Yin Y, Xu Y. 2014. New insights into clostridia through comparative analyses of their 40 genomes. BioEnergy Res 7:1481–1492 http://dx.doi.org/10.1007/s12155-014-9486-9.
101. Sievers F, Wilm A, Dineen D, Gibson TJ, Karplus K, Li W, Lopez R, McWilliam H, Remmert M, Söding J, Thompson JD, Higgins DG. 2011. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol 7:539 http://dx.doi.org/10.1038/msb.2011.75. [PubMed]
102. Hoang DT, Chernomor O, von Haeseler A, Minh BQ, Vinh LS. 2018. UFBoot2: improving the ultrafast bootstrap approximation. Mol Biol Evol 35:518–522 http://dx.doi.org/10.1093/molbev/msx281. [PubMed]
103. Nguyen L-T, Schmidt HA, von Haeseler A, Minh BQ. 2015. IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. Mol Biol Evol 32:268–274 http://dx.doi.org/10.1093/molbev/msu300. [PubMed]
104. Smith TJ, Hill KK, Xie G, Foley BT, Williamson CHD, Foster JT, Johnson SL, Chertkov O, Teshima H, Gibbons HS, Johnsky LA, Karavis MA, Smith LA. 2015. Genomic sequences of six botulinum neurotoxin-producing strains representing three clostridial species illustrate the mobility and diversity of botulinum neurotoxin genes. Infect Genet Evol 30:102–113 http://dx.doi.org/10.1016/j.meegid.2014.12.002. [PubMed]
105. Halpin JL, Hill K, Johnson SL, Bruce DC, Shirey TB, Dykes JK, Lúquez C. 2017. Finished whole-genome sequences of Clostridium butyricum toxin subtype E4 and Clostridium baratii toxin subtype F7 strains. Genome Announc 5:e00375-17. [PubMed]
106. Sebaihia M, Peck MW, Minton NP, Thomson NR, Holden MTG, Mitchell WJ, Carter AT, Bentley SD, Mason DR, Crossman L, Paul CJ, Ivens A, Wells-Bennik MHJ, Davis IJ, Cerdeño-Tárraga AM, Churcher C, Quail MA, Chillingworth T, Feltwell T, Fraser A, Goodhead I, Hance Z, Jagels K, Larke N, Maddison M, Moule S, Mungall K, Norbertczak H, Rabbinowitsch E, Sanders M, Simmonds M, White B, Whithead S, Parkhill J. 2007. Genome sequence of a proteolytic (group I) Clostridium botulinum strain Hall A and comparative analysis of the clostridial genomes. Genome Res 17:1082–1092 http://dx.doi.org/10.1101/gr.6282807. [PubMed]
107. Woudstra C, Le Maréchal C, Souillard R, Bayon-Auboyer M-H, Mermoud I, Desoutter D, Fach P. 2016. New insights into the genetic diversity of Clostridium botulinum group III through extensive genome exploration. Front Microbiol 7:757 http://dx.doi.org/10.3389/fmicb.2016.00757. [PubMed]
108. Hassan KA, Elbourne LDH, Tetu SG, Johnson EA, Paulsen IT. 2014. Genome sequence of the neurotoxigenic Clostridium butyricum strain 5521. Genome Announc 2:e00632-14 http://dx.doi.org/10.1128/genomeA.00632-14. [PubMed]
109. Knetsch CW, Kumar N, Forster SC, Connor TR, Browne HP, Harmanus C, Sanders IM, Harris SR, Turner L, Morris T, Perry M, Miyajima F, Roberts P, Pirmohamed M, Songer JG, Weese JS, Indra A, Corver J, Rupnik M, Wren BW, Riley TV, Kuijper EJ, Lawley TD. 2018. Zoonotic transfer of Clostridium difficile harboring antimicrobial resistance between farm animals and humans. J Clin Microbiol 56:e01384-17. [PubMed]
110. Saeb AT, Abouelhoda M, Selvaraju M, Althawadi SI, Mutabagani M, Adil M, Al Hokail A, Tayeb HT. 2017. The use of next-generation sequencing in the identification of a fastidious pathogen: a lesson from a clinical setup. Evol Bioinform Online 12:1176934316686072. [PubMed]
111. Bettegowda C, Huang X, Lin J, Cheong I, Kohli M, Szabo SA, Zhang X, Diaz LA Jr, Velculescu VE, Parmigiani G, Kinzler KW, Vogelstein B, Zhou S. 2006. The genome and transcriptomes of the anti-tumor agent Clostridium novyi-NT. Nat Biotechnol 24:1573–1580 http://dx.doi.org/10.1038/nbt1256. [PubMed]
112. Shimizu T, Ohtani K, Hirakawa H, Ohshima K, Yamashita A, Shiba T, Ogasawara N, Hattori M, Kuhara S, Hayashi H. 2002. Complete genome sequence of Clostridium perfringens, an anaerobic flesh-eater. Proc Natl Acad Sci U S A 99:996–1001 http://dx.doi.org/10.1073/pnas.022493799. [PubMed]
113. Brüggemann H, Bäumer S, Fricke WF, Wiezer A, Liesegang H, Decker I, Herzberg C, Martínez-Arias R, Merkl R, Henne A, Gottschalk G. 2003. The genome sequence of Clostridium tetani, the causative agent of tetanus disease. Proc Natl Acad Sci U S A 100:1316–1321 http://dx.doi.org/10.1073/pnas.0335853100. [PubMed]
114. Honkalas VS, Dabir AP, Arora P, Ranade DR, Dhakephalkar PK. 2015. Draft genome sequence of Clostridium celerecrescens 152B isolated from sub-seafloor methane hydrate deposits. Mar Genomics 21:23–24 http://dx.doi.org/10.1016/j.margen.2015.01.008. [PubMed]
115. Chia J-H, Feng Y, Su L-H, Wu T-L, Chen C-L, Liang Y-H, Chiu C-H. 2017. Clostridium innocuum is a significant vancomycin-resistant pathogen for extraintestinal clostridial infection. Clin Microbiol Infect 23:560–566 http://dx.doi.org/10.1016/j.cmi.2017.02.025. [PubMed]
116. Poehlein A, Riegel K, König SM, Leimbach A, Daniel R, Dürre P. 2015. Genome sequence of Clostridium sporogenes DSM 795(T), an amino acid-degrading, nontoxic surrogate of neurotoxin-producing Clostridium botulinum. Stand Genomic Sci 10:40 http://dx.doi.org/10.1186/s40793-015-0016-y. [PubMed]
117. Cambridge JM, Blinkova AL, Salvador Rocha EI, Bode Hernández A, Moreno M, Ginés-Candelaria E, Goetz BM, Hunicke-Smith S, Satterwhite E, Tucker HO, Walker JR. 2018. Genomics of Clostridium taeniosporum, an organism which forms endospores with ribbon-like appendages. PLoS One 13:e0189673 http://dx.doi.org/10.1371/journal.pone.0189673. [PubMed]
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/content/journal/microbiolspec/10.1128/microbiolspec.GPP3-0033-2018
2019-06-21
2019-08-25

Abstract:

Whole-genome sequences are now available for all the clinically important clostridia and many of the lesser or opportunistically pathogenic clostridia. The complex clade structures of , , and the species that produce botulinum toxins have been delineated by whole-genome sequence analysis. The true clostridia of cluster I show relatively low levels of gross genomic rearrangements within species, in contrast to the species of cluster XI, notably , which have been found to have very plastic genomes with significant levels of chromosomal rearrangement. Throughout the clostridial phylotypes, a large proportion of the strain diversity is driven by the acquisition and loss of mobile elements, including phages, plasmids, insertion sequences, and transposons. Genomic analysis has been used to investigate the diversity and spread of within hospital settings, the zoonotic transfer of isolates, and the emergence, origins, and geographic spread of epidemic ribotypes. In the clades defined by chromosomal sequence analysis show no indications of clustering based on host species or geographical location. Whole-genome sequence analysis helps to define the different survival and pathogenesis strategies that the clostridia use. Some, such as , produce toxins which rapidly act to kill the host, whereas others, such as and , produce less lethal toxins which can damage tissue but do not rapidly kill the host. The genomes provide a resource that can be mined to identify potential vaccine antigens and targets for other forms of therapeutic intervention.

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Figures

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FIGURE 1

Relationships within the . Maximum likelihood tree of 16S rRNA genes of members of the family. 16S small subunit rRNA gene sequences were retrieved from RDP (release 11) and NCBI:GenBank (http://www.ncbi.nlm.nih.gov/). Sequences were aligned using Clustal Omega. The multiple sequence alignment was used to build a maximum likelihood tree using IQ-TREE with the general time reversible model (GTR+F+G6) and rapid bootstrapping (-bb 2000) nonparametric bootstraps (-v) ( 101 103 ). Clusters are labeled corresponding to the groups proposed in Collins et al. and genus groups as proposed by Parks et al. ( 7 , 8 ). Clusters from Collins et al. that are not included are due to reclassification outside of the family.

Source: microbiolspec June 2019 vol. 7 no. 3 doi:10.1128/microbiolspec.GPP3-0033-2018
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Image of FIGURE 2
FIGURE 2

Relationships within . Maximum likelihood tree of 16s rRNA genes of members of the genus . 16S small subunit rRNA gene sequences were retrieved from RDP (release 11) and NCBI:GenBank (http://www.ncbi.nlm.nih.gov/). Sequences were aligned using Clustal Omega. The multiple sequence alignment was used to build a maximum likelihood tree using IQ-TREE with the general time reversible model (GTR+F+G6) and rapid bootstrapping (-bb 2000) nonparametric bootstraps (-v) ( 101 103 ). Clusters are labeled corresponding to the groups proposed in Collins et al. ( 8 ). groups I to IV are labeled.

Source: microbiolspec June 2019 vol. 7 no. 3 doi:10.1128/microbiolspec.GPP3-0033-2018
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Tables

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TABLE 1

Pathogenic clostridial genomes available in GenBank

Source: microbiolspec June 2019 vol. 7 no. 3 doi:10.1128/microbiolspec.GPP3-0033-2018
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TABLE 2

Phenotypic groups of

Source: microbiolspec June 2019 vol. 7 no. 3 doi:10.1128/microbiolspec.GPP3-0033-2018
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TABLE 3

Presence and absence of toxins within toxinotypes

Source: microbiolspec June 2019 vol. 7 no. 3 doi:10.1128/microbiolspec.GPP3-0033-2018

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