1887

Abstract

Hypermutable simple sequence repeats (SSRs) are drivers of phase variation (PV) whose stochastic, high-frequency, reversible switches in gene expression are a common feature of several pathogenic bacterial species, including the human pathogen Campylobacter jejuni. Here we examine the distribution and conservation of known and putative SSR-driven phase variable genes – the phasome – in the genus Campylobacter. PhasomeIt, a new program, was specifically designed for rapid identification of SSR-mediated PV. This program detects the location, type and repeat number of every SSR. Each SSR is linked to a specific gene and its putative expression state. Other outputs include conservation of SSR-driven phase-variable genes and the ‘core phasome’ – the minimal set of PV genes in a phylogenetic grouping. Analysis of 77 complete Campylobacter genome sequences detected a ‘core phasome’ of conserved PV genes in each species and a large number of rare PV genes with few, or no, homologues in other genome sequences. Analysis of a set of partial genome sequences, with food-chain-associated metadata, detected evidence of a weak link between phasome and source host for disease-causing isolates of sequence type (ST)-828 but not the ST-21 or ST-45 complexes. Investigation of the phasomes in the genus Campylobacter provided evidence of overlapping but distinctive mechanisms of PV-mediated adaptation to specific niches. This suggests that the phasome could be involved in host adaptation and spread of campylobacters. Finally, this tool is malleable and will have utility for studying the distribution and genic effects of other repetitive elements in diverse bacterial species.

  • This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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2018-10-23
2024-04-19
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References

  1. van der Woude MW, Bäumler AJ. Phase and antigenic variation in bacteria. Clin Microbiol Rev 2004; 17:581–611 [View Article][PubMed]
    [Google Scholar]
  2. Bayliss CD, Palmer ME. Evolution of simple sequence repeat-mediated phase variation in bacterial genomes. Ann N Y Acad Sci 2012; 1267:39–44 [View Article][PubMed]
    [Google Scholar]
  3. Cooper KK, Cooper MA, Zuccolo A, Joens LA. Re-sequencing of a virulent strain of Campylobacter jejuni NCTC11168 reveals potential virulence factors. Res Microbiol 2013; 164:6–11 [View Article][PubMed]
    [Google Scholar]
  4. Oldfield NJ, Matar S, Bidmos FA, Alamro M, Neal KR et al. Prevalence and phase variable expression status of two autotransporters, NalP and MspA, in carriage and disease isolates of Neisseria meningitidis. PLoS One 2013; 8:e69746 [View Article][PubMed]
    [Google Scholar]
  5. Aidley J. Genomics and Population Dynamics of Phase Variable Genes In campylobacter University of Leicester; 2017
    [Google Scholar]
  6. Wanford JJ, Green LR, Aidley J, Bayliss CD. Phasome analysis of pathogenic and commensal Neisseria species expands the known repertoire of phase variable genes, and highlights common adaptive strategies. PLoS One 2018; 13:e0196675 [View Article][PubMed]
    [Google Scholar]
  7. Moxon R, Bayliss C, Hood D. Bacterial contingency loci: the role of simple sequence DNA repeats in bacterial adaptation. Annu Rev Genet 2006; 40:307–333 [View Article][PubMed]
    [Google Scholar]
  8. Lecuit M, Abachin E, Martin A, Poyart C, Pochart P et al. Immunoproliferative small intestinal disease associated with Campylobacter jejuni. N Engl J Med 2004; 350:239–248 [View Article][PubMed]
    [Google Scholar]
  9. Tam CC, O'Brien SJ, Adak GK, Meakins SM, Frost JA. Campylobacter coli - an important foodborne pathogen. J Infect 2003; 47:28–32 [View Article][PubMed]
    [Google Scholar]
  10. Burgos-Portugal JA, Kaakoush NO, Raftery MJ, Mitchell HM. Pathogenic potential of Campylobacter ureolyticus. Infect Immun 2012; 80:883–890 [View Article][PubMed]
    [Google Scholar]
  11. Jones K. Campylobacters in water, sewage and the environment. Symp Ser Soc Appl Microbiol 2001; 90:68S–79 [View Article][PubMed]
    [Google Scholar]
  12. O'Leary J, Corcoran D, Lucey B. Comparison of the EntericBio multiplex PCR system with routine culture for detection of bacterial enteric pathogens. J Clin Microbiol 2009; 47:3449–3453 [View Article][PubMed]
    [Google Scholar]
  13. O'Donovan D, Corcoran GD, Lucey B, Sleator RD. Campylobacter ureolyticus: a portrait of the pathogen. Virulence 2014; 5:498–506 [View Article][PubMed]
    [Google Scholar]
  14. Gebhart CJ, Edmonds P, Ward GE, Kurtz HJ, Brenner DJ. "Campylobacter hyointestinalis" sp. nov.: a new species of Campylobacter found in the intestines of pigs and other animals. J Clin Microbiol 1985; 21:715–720[PubMed]
    [Google Scholar]
  15. On SL, Bloch B, Holmes B, Hoste B, Vandamme P. Campylobacter hyointestinalis subsp. lawsonii subsp. nov., isolated from the porcine stomach, and an emended description of Campylobacter hyointestinalis. Int J Syst Bacteriol 1995; 45:767–774 [View Article][PubMed]
    [Google Scholar]
  16. Yahara K, Méric G, Taylor AJ, de Vries SP, Murray S et al. Genome-wide association of functional traits linked with Campylobacter jejuni survival from farm to fork. Environ Microbiol 2017; 19:361–380 [View Article][PubMed]
    [Google Scholar]
  17. Sheppard SK, Didelot X, Meric G, Torralbo A, Jolley KA et al. Genome-wide association study identifies vitamin B5 biosynthesis as a host specificity factor in Campylobacter. Proc Natl Acad Sci USA 2013; 110:11923–11927 [View Article][PubMed]
    [Google Scholar]
  18. Gilbert MJ, Miller WG, Yee E, Zomer AL, van der Graaf-van Bloois L et al. Comparative genomics of Campylobacter fetus from reptiles and mammals reveals divergent evolution in host-associated lineages. Genome Biol Evol 2016; 8:2006–2019 [View Article][PubMed]
    [Google Scholar]
  19. Lin WH, Kussell E. Evolutionary pressures on simple sequence repeats in prokaryotic coding regions. Nucleic Acids Res 2012; 40:2399–2413 [View Article][PubMed]
    [Google Scholar]
  20. Wanford JJ, Lango-Scholey L, Nothaft H, Hu Y, Szymanski CM et al. Random sorting of Campylobacter jejuni phase variants due to a narrow bottleneck during colonization of broiler chickens. Microbiology 2018; 164:896–907 [View Article][PubMed]
    [Google Scholar]
  21. Bayliss CD, Bidmos FA, Anjum A, Manchev VT, Richards RL et al. Phase variable genes of Campylobacter jejuni exhibit high mutation rates and specific mutational patterns but mutability is not the major determinant of population structure during host colonization. Nucleic Acids Res 2012; 40:5876–5889 [View Article][PubMed]
    [Google Scholar]
  22. Cock PJ, Antao T, Chang JT, Chapman BA, Cox CJ et al. Biopython: freely available Python tools for computational molecular biology and bioinformatics. Bioinformatics 2009; 25:1422–1423 [View Article][PubMed]
    [Google Scholar]
  23. Merkel A, Gemmell NJ. Detecting microsatellites in genome data: variance in definitions and bioinformatic approaches cause systematic bias. Evol Bioinform Online 2008; 4:1–6 [View Article][PubMed]
    [Google Scholar]
  24. Benson DA, Cavanaugh M, Clark K, Karsch-Mizrachi I, Lipman DJ et al. GenBank. Nucleic Acids Res 2013; 41:D36–D42 [View Article][PubMed]
    [Google Scholar]
  25. Brocchieri L, Karlin S. Protein length in eukaryotic and prokaryotic proteomes. Nucleic Acids Res 2005; 33:3390–3400 [View Article][PubMed]
    [Google Scholar]
  26. Talevich E, Invergo BM, Cock PJ, Chapman BA. Bio.Phylo: a unified toolkit for processing, analyzing and visualizing phylogenetic trees in Biopython. BMC Bioinformatics 2012; 13:209 [View Article][PubMed]
    [Google Scholar]
  27. Thomas DK, Lone AG, Selinger LB, Taboada EN, Uwiera RR et al. Comparative variation within the genome of Campylobacter jejuni NCTC 11168 in human and murine hosts. PLoS One 2014; 9:e88229 [View Article][PubMed]
    [Google Scholar]
  28. Revez J, Schott T, Rossi M, Hänninen ML. Complete genome sequence of a variant of Campylobacter jejuni NCTC 11168. J Bacteriol 2012; 194:6298–6299 [View Article][PubMed]
    [Google Scholar]
  29. Skarp CP, Akinrinade O, Nilsson AJ, Ellström P, Myllykangas S et al. Comparative genomics and genome biology of invasive Campylobacter jejuni. Sci Rep 2015; 5:17300 [View Article][PubMed]
    [Google Scholar]
  30. Sheppard SK, Cheng L, Méric G, de Haan CP, Llarena AK et al. Cryptic ecology among host generalist Campylobacter jejuni in domestic animals. Mol Ecol 2014; 23:2442–2451 [View Article][PubMed]
    [Google Scholar]
  31. Parkhill J, Wren BW, Mungall K, Ketley JM, Churcher C et al. The genome sequence of the food-borne pathogen Campylobacter jejuni reveals hypervariable sequences. Nature 2000; 403:665–668 [View Article][PubMed]
    [Google Scholar]
  32. Pearson BM, Rokney A, Crossman LC, Miller WG, Wain J et al. Complete genome sequence of the Campylobacter coli clinical isolate 15-537360. Genome Announc 2013; 1:e01056 [View Article][PubMed]
    [Google Scholar]
  33. Henderson IR, Owen P, Nataro JP. Molecular switches–the ON and OFF of bacterial phase variation. Mol Microbiol 1999; 33:919–932 [View Article][PubMed]
    [Google Scholar]
  34. Saunders NJ, Peden JF, Hood DW, Moxon ER. Simple sequence repeats in the Helicobacter pylori genome. Mol Microbiol 1998; 27:1091–1098 [View Article][PubMed]
    [Google Scholar]
  35. de Bolle X, Bayliss CD, Field D, van de Ven T, Saunders NJ et al. The length of a tetranucleotide repeat tract in Haemophilus influenzae determines the phase variation rate of a gene with homology to type III DNA methyltransferases. Mol Microbiol 2000; 35:211–222 [View Article][PubMed]
    [Google Scholar]
  36. Hitchen P, Brzostek J, Panico M, Butler JA, Morris HR et al. Modification of the Campylobacter jejuni flagellin glycan by the product of the Cj1295 homopolymeric-tract-containing gene. Microbiology 2010; 156:1953–1962 [View Article][PubMed]
    [Google Scholar]
  37. Karlyshev AV, Linton D, Gregson NA, Wren BW. A novel paralogous gene family involved in phase-variable flagella-mediated motility in Campylobacter jejuni. Microbiology 2002; 148:473–480 [View Article][PubMed]
    [Google Scholar]
  38. van Alphen LB, Wuhrer M, Bleumink-Pluym NM, Hensbergen PJ, Deelder AM et al. A functional Campylobacter jejuni maf4 gene results in novel glycoforms on flagellin and altered autoagglutination behaviour. Microbiology 2008; 154:3385–3397 [View Article][PubMed]
    [Google Scholar]
  39. Sheppard SK, Colles FM, Carthy N, Strachan NJC, Ogden ID et al. Niche segregation and genetic structure of Campylobacter jejuni populations from wild and agricultural host species; 20113484–3490
  40. Sheppard SK, Colles F, Richardson J, Cody AJ, Elson R et al. Host association of Campylobacter genotypes transcends geographic variation; 2010; 765269–5277
  41. Lango-Scholey L, Aidley J, Woodacre A, Jones MA, Bayliss CD. High throughput method for analysis of repeat number for 28 phase variable loci of Campylobacter jejuni strain NCTC11168. PLoS One 2016; 11:e0159634 [View Article][PubMed]
    [Google Scholar]
  42. Aidley J, Rajopadhye S, Akinyemi NM, Lango-Scholey L, Jones MA et al. Nonselective bottlenecks control the divergence and diversification of phase-variable bacterial populations. MBio 2017; 8:e00878-17 [View Article][PubMed]
    [Google Scholar]
  43. Artymovich K, Kim JS, Linz JE, Hall DF, Kelley LE et al. A "successful allele" at Campylobacter jejuni contingency locus Cj0170 regulates motility; "successful alleles" at locus Cj0045 are strongly associated with mouse colonization. Food Microbiol 2013; 34:425–430 [View Article][PubMed]
    [Google Scholar]
  44. Libby E, Rainey PB. Exclusion rules, bottlenecks and the evolution of stochastic phenotype switching. Proc Biol Sci 2011; 278:3574–3583 [View Article][PubMed]
    [Google Scholar]
  45. Patra P, Klumpp S. Emergence of phenotype switching through continuous and discontinuous evolutionary transitions. Phys Biol 2015; 12:046004 [View Article][PubMed]
    [Google Scholar]
  46. McNally DJ, Lamoureux MP, Karlyshev AV, Fiori LM, Li J et al. Commonality and biosynthesis of the O-methyl phosphoramidate capsule modification in Campylobacter jejuni. J Biol Chem 2007; 282:28566–28576 [View Article][PubMed]
    [Google Scholar]
  47. Sørensen MC, van Alphen LB, Harboe A, Li J, Christensen BB et al. Bacteriophage F336 recognizes the capsular phosphoramidate modification of Campylobacter jejuni NCTC11168. J Bacteriol 2011; 193:6742–6749 [View Article][PubMed]
    [Google Scholar]
  48. Aidley J, Sørensen MCH, Bayliss CD, Brøndsted L. Phage exposure causes dynamic shifts in the expression states of specific phase-variable genes of Campylobacter jejuni. Microbiology 2017; 163:911–919 [View Article][PubMed]
    [Google Scholar]
  49. Ryan KA, Lo RY. Characterization of a CACAG pentanucleotide repeat in Pasteurella haemolytica and its possible role in modulation of a novel type III restriction-modification system. Nucleic Acids Res 1999; 27:1505–1511 [View Article][PubMed]
    [Google Scholar]
  50. Anjum A, Brathwaite KJ, Aidley J, Connerton PL, Cummings NJ et al. Phase variation of a Type IIG restriction-modification enzyme alters site-specific methylation patterns and gene expression in Campylobacter jejuni strain NCTC11168. Nucleic Acids Res 2016; 44:4581–4594 [View Article][PubMed]
    [Google Scholar]
  51. Manso AS, Chai MH, Atack JM, Furi L, de Ste Croix M et al. A random six-phase switch regulates pneumococcal virulence via global epigenetic changes. Nat Commun 2014; 5:5055 [View Article][PubMed]
    [Google Scholar]
  52. Bayliss CD, Callaghan MJ, Moxon ER. High allelic diversity in the methyltransferase gene of a phase variable type III restriction-modification system has implications for the fitness of Haemophilus influenzae. Nucleic Acids Res 2006; 34:4046–4059 [View Article][PubMed]
    [Google Scholar]
  53. Seib KL, Peak IR, Jennings MP. Phase variable restriction-modification systems in Moraxella catarrhalis. FEMS Immunol Med Microbiol 2002; 32:159–165[PubMed]
    [Google Scholar]
  54. Snipen L, Ussery DW. Standard operating procedure for computing pangenome trees. Stand Genomic Sci 2010; 2:135–141 [View Article][PubMed]
    [Google Scholar]
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