Comparative Genomics and Transcriptomics of Organohalide-Respiring Bacteria and Regulation of rdh Gene Transcription

  • Thomas Kruse
  • Hauke Smidt
  • Ute LechnerEmail author


Comparison of the genomes of organohalide-respiring bacteria has improved our understanding of the genetic background of the organohalide respiration process. In this chapter the remarkable differences between obligate and facultative organohalide-respiring bacteria in the number of reductive dehalogenase-encoding genes and the numbers and types of accessory genes are discussed in relation to different lifestyles and evolutionary aspects. Furthermore, the putative function of accessory genes is discussed and a unifying nomenclature is proposed. The genomes also reflect distinct mechanisms for the synthesis or acquisition of the corrinoid cofactors of reductive dehalogenases , which are well in accord with the observed growth requirements of the respective organohalide-respiring bacteria. The value of microarray-based comparative genomics, transcriptomics, and quantitative transcription analyses for understanding the physiology and environmental significance of organohalide respiration is discussed. The reductive dehalogenase genes are in general associated with genes encoding transcriptional regulators, which are likely involved in sensing the halogenated electron acceptors. The role of two types of regulators in transcriptional regulation of organohalide respiration has been investigated. A multiple antibiotic resistance regulator (MarR)-type regulator was shown to regulate negatively the transcription of reductive dehalogenase genes in Dehalococcoides mccartyi. In Desulfitobacterium hafniense, the cAMP receptor protein/fumarate and nitrate reduction (CRP/FNR) regulator, CprK , activates transcription of reductive dehalogenase genes. The molecular mechanism of how ortho-chlorophenols act as effectors has been elucidated and how, through the induction of structural changes, they lead to DNA binding of the regulator.


Twin Arginine Translocation Reductive Dehalogenases Desulfitobacterium Hafniense Strain CBDB1 Organohalide Respiration 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was funded by the German Research Foundation (DFG research unit FOR 1530). Work of HS and TK was financially supported by the EcoLinc Project of the Netherlands Genomics Initiative, the BE-BASIC foundation through projects F07.001.05 and F08.004.01, as well as the European Community program FP7 (grants KBBE-211684; BACSIN, and KBBE-222625; METAEXPLORE). We are grateful to Gary Sawers for comments on the manuscript.


  1. Ahsanul Islam M, Edwards EA, Mahadevan R (2010) Characterizing the metabolism of Dehalococcoides with a constraint-based model. PLoS Comput Biol 6(8). doi: 10.1371/journal.pcbi.1000887
  2. Amos BK, Ritalahti KM, Cruz-Garcia C, Padilla-Crespo E, Löffler FE (2008) Oxygen effect on Dehalococcoides viability and biomarker quantification. Environ Sci Technol 42(15):5718–5726PubMedCrossRefGoogle Scholar
  3. Baelum J, Chambon JC, Scheutz C, Binning PJ, Laier T, Bjerg PL, Jacobsen CS (2013) A conceptual model linking functional gene expression and reductive dechlorination rates of chlorinated ethenes in clay rich groundwater sediment. Water Res 47(7):2467–2478. doi: 10.1016/j.watres.2013.02.016 PubMedCrossRefGoogle Scholar
  4. Banerjee R, Ragsdale SW (2003) The many faces of vitamin B12: catalysis by cobalamin-dependent enzymes. Annu Rev Biochem 72:209–247PubMedCrossRefGoogle Scholar
  5. Behrens S, Azizian MF, McMurdie PJ, Sabalowsky A, Dolan ME, Semprini L, Spormann AM (2008) Monitoring abundance and expression of “Dehalococcoides” species chloroethene-reductive dehalogenases in a tetrachloroethene-dechlorinating flow column. Appl Environ Microbiol 74(18):5695–5703. doi: 10.1128/AEM.00926-08 PubMedPubMedCentralCrossRefGoogle Scholar
  6. Bisaillon A, Beaudet R, Lépine F, Deziel E, Villemur R (2010) Identification and characterization of a novel CprA reductive dehalogenase specific to highly chlorinated phenols from Desulfitobacterium hafniense strain PCP-1. Appl Environ Microbiol 76(22):7536–7540. doi: 10.1128/AEM.01362-10 PubMedPubMedCentralCrossRefGoogle Scholar
  7. Bisaillon A, Beaudet R, Lépine F, Villemur R (2011) Quantitative analysis of the relative transcript levels of four chlorophenol reductive dehalogenase genes in Desulfitobacterium hafniense PCP-1 exposed to chlorophenols. Appl Environ Microbiol 77(17):6261–6264. doi: 10.1128/AEM.00390-11 PubMedPubMedCentralCrossRefGoogle Scholar
  8. Borths EL, Locher KP, Lee AT, Rees DC (2002) The structure of Escherichia coli BtuF and binding to its cognate ATP binding cassette transporter. Proc Natl Acad Sci USA 99(26):16642–16647. doi: 10.1073/pnas.262659699 PubMedPubMedCentralCrossRefGoogle Scholar
  9. Boyer A, Pagé-Bélanger R, Saucier M, Villemur R, Lépine F, Juteau P, Beaudet R (2003) Purification, cloning and sequencing of an enzyme mediating the reductive dechlorination of 2,4,6-trichlorophenol from Desulfitobacterium frappieri PCP-1. Biochem J 373(1):297–303PubMedPubMedCentralCrossRefGoogle Scholar
  10. Cheng D, He JZ (2009) Isolation and characterization of “Dehalococcoides” sp. strain MB, which dechlorinates tetrachloroethene to trans-1,2-dichloroethene. Appl Environ Microbiol 75(18):5910–5918. doi: 10.1128/Aem.00767-09 PubMedPubMedCentralCrossRefGoogle Scholar
  11. Choudhary PK, Duret A, Rohrbach-Brandt E, Holliger C, Sigel RKO, Maillard J (2013) Diversity of cobalamin riboswitches in the corrinoid-producing organohalide respirer Desulfitobacterium hafniense. J Bacteriol 195(22):5186–5195. doi: 10.1128/jb.00730-13 PubMedPubMedCentralCrossRefGoogle Scholar
  12. Chow WL, Cheng D, Wang S, He J (2010) Identification and transcriptional analysis of trans-DCE-producing reductive dehalogenases in Dehalococcoides species. ISME J 4(8):1020–1030. doi: 10.1038/ismej.2010.27 PubMedCrossRefGoogle Scholar
  13. Christiansen N, Ahring BK (1996) Desulfitobacterium hafniense sp. nov., an anaerobic, reductively dechlorinating bacterium. Int J Syst Bacteriol 46(2):442–448CrossRefGoogle Scholar
  14. Christiansen N, Ahring BK, Wohlfarth G, Diekert G (1998) Purification and characterization of the 3-chloro-4-hydroxy-phenylacetate reductive dehalogenase of Desulfitobacterium hafniense. FEBS Lett 436(2):159–162PubMedCrossRefGoogle Scholar
  15. Claas KR, Parrish JR, Maggio-Hall LA, Escalante-Semerena JC (2010) Functional analysis of the nicotinate mononucleotide: 5,6-dimethylbenzimidazole phosphoribosyltransferase (CobT) enzyme, involved in the late steps of coenzyme B12 biosynthesis in Salmonella enterica. J Bacteriol 192(1):145–154PubMedCrossRefGoogle Scholar
  16. Coates ARM, Shinnick TM, Ellis RJ (1993) Chaperonin nomenclature. Mol Microbiol 8(4):787PubMedCrossRefGoogle Scholar
  17. Cuypers H, Viebrock-Sambale A, Zumft WG (1992) NosR, a membrane-bound regulatory component necessary for expression of nitrous oxide reductase in denitrifying Pseudomonas stutzeri. J Bacteriol 174(16):5332–5339PubMedPubMedCentralGoogle Scholar
  18. de Crécy-Lagard V, Forouhar F, Brochier-Armanet C, Tong L, Hunt JF (2012) Comparative genomic analysis of the DUF71/COG2102 family predicts roles in diphthamide biosynthesis and B12 salvage. Biol Direct 7:32PubMedPubMedCentralCrossRefGoogle Scholar
  19. Deshpande NP, Wong YK, Mansfield M, Wilkins MR, Lee M (2013) Genome sequence of Dehalobacter UNSWDHB, a chloroform-dechlorinating bacterium. Genome Announc 1(5):e00720–e00713. doi: 10.1128/genomeA.00720-13 PubMedPubMedCentralCrossRefGoogle Scholar
  20. Dos Santos PC, Fang Z, Mason SW, Setubal JC, Dixon R (2012) Distribution of nitrogen fixation and nitrogenase-like sequences amongst microbial genomes. BMC Genomics 13(1):162PubMedPubMedCentralCrossRefGoogle Scholar
  21. Duret A, Holliger C, Maillard J (2012) The physiological opportunism of Desulfitobacterium hafniense strain TCE1 towards organohalide respiration with tetrachloroethene. Appl Environ Microbiol 78(17):6121–6127. doi: 10.1128/AEM.01221-12 PubMedPubMedCentralCrossRefGoogle Scholar
  22. Finn RD, Bateman A, Clements J, Coggill P, Eberhardt RY, Eddy SR, Heger A, Hetherington K, Holm L, Mistry J, Sonnhammer ELL, Tate J, Punta M (2014) Pfam: the protein families database. Nucleic Acids Res 42(D1):D222–D230. doi: 10.1093/nar/gkt1223 PubMedCrossRefGoogle Scholar
  23. Finneran KT, Forbush HM, VanPraagh CV, Lovley DR (2002) Desulfitobacterium metallireducens sp. nov., an anaerobic bacterium that couples growth to the reduction of metals and humic acids as well as chlorinated compounds. Int J Syst Evol Microbiol 52(Pt 6):1929–1935Google Scholar
  24. Fleischmann RD, Adams MD, White O, Clayton RA, Kirkness EF, Kerlavage AR, Bult CJ, Tomb JF, Dougherty BA, Merrick JM, McKenney K, Sutton G, FitzHugh W, Fields C, Gocayne JD, Scott J, Shirley R, Liu LI, Venter JC (1995) Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science 269(5223):496–521PubMedCrossRefGoogle Scholar
  25. Fletcher KE, Costanza J, Cruz-Garcia C, Ramaswamy NS, Pennell KD, Löffler FE (2011) Effects of elevated temperature on Dehalococcoides dechlorination performance and DNA and RNA biomarker abundance. Environ Sci Technol 45(2):712–718. doi: 10.1021/es1023477 PubMedCrossRefGoogle Scholar
  26. Fung JM, Morris RM, Adrian L, Zinder SH (2007) Expression of reductive dehalogenase genes in Dehalococcoides ethenogenes strain 195 growing on tetrachloroethene, trichloroethene, or 2,3-dichlorophenol. Appl Environ Microbiol 73(14):4439–4445. doi: 10.1128/AEM.00215-07 PubMedPubMedCentralCrossRefGoogle Scholar
  27. Futagami T, Goto M, Furukawa K (2008) Biochemical and genetic bases of dehalorespiration. Chem Rec 8(1):1–12PubMedCrossRefGoogle Scholar
  28. Futagami T, Goto M, Furukawa K (2014) Genetic systems of organohalide-respiring bacteria. In: Nojiri H, Tsuda M, Fukuda M, Kamagata Y (eds) Biodegradative bacteria. How bacteria degrade, survive, adapt and evolve. Springer, Tokyo, pp 59–81. doi: 10.1007/978-4-431-54520-0
  29. Futamata H, Kaiya S, Sugawara M, Hiraishi A (2009) Phylogenetic and transcriptional analyses of a tetrachloroethene-dechlorinating “Dehalococcoides” enrichment culture TUT2264 and its reductive-dehalogenase genes. Microbes Environ 24(4):330–337PubMedCrossRefGoogle Scholar
  30. Gábor K, Verissimo CS, Cyran BC, Ter Horst P, Meijer NP, Smidt H, de Vos WM, van der Oost J (2006) Characterization of CprK1, a CRP/FNR-type transcriptional regulator of halorespiration from Desulfitobacterium hafniense. J Bacteriol 188(7):2604–2613. doi: 10.1128/JB.188.7.2604-2613.2006 PubMedPubMedCentralCrossRefGoogle Scholar
  31. Gábor K, Hailesellasse Sene K, Smidt H, de Vos WM, van der Oost J (2008) Divergent roles of CprK paralogues from Desulfitobacterium hafniense in activating gene expression. Microbiology 154(Pt 12):3686–3696. doi: 10.1099/mic.0.2008/021584-0 PubMedCrossRefGoogle Scholar
  32. Gao R, Stock AM (2009) Biological insights from structures of two-component proteins. Annu Rev Microbiol 63:133–154PubMedPubMedCentralCrossRefGoogle Scholar
  33. Gerritse J, Drzyzga O, Kloetstra G, Keijmel M, Wiersum LP, Hutson R, Collins MD, Gottschal JC (1999) Influence of different electron donors and acceptors on dehalorespiration of tetrachloroethene by Desulfitobacterium frappieri TCE1. Appl Environ Microbiol 65(12):5212–5221PubMedPubMedCentralGoogle Scholar
  34. Goris T, Schubert T, Gadkari J, Wubet T, Tarkka M, Buscot F, Adrian L, Diekert G (2014) Insights into organohalide respiration and the versatile catabolism of Sulfurospirillum multivorans gained from comparative genomics and physiological studies. Environ Microbiol 16(11):3562–3580. doi: 10.1111/1462-2920.12589 PubMedCrossRefGoogle Scholar
  35. Goris T, Hornung B, Kruse T, Reinhold A, Westermann M, Schaap PJ, Smidt H, Diekert G (2015) Draft genome sequence and characterization of Desulfitobacterium hafniense PCE-S. Stand Genomic Sci 10:15. doi: 10.1186/1944-3277-10-15 PubMedPubMedCentralCrossRefGoogle Scholar
  36. Gray MJ, Tavares NK, Escalante-Semerena JC (2008) The genome of Rhodobacter sphaeroides strain 2.4.1 encodes functional cobinamide salvaging systems of archaeal and bacterial origins. Mol Microbiol 70(4):824–836PubMedPubMedCentralGoogle Scholar
  37. Gray MJ, Escalante-Semerena JC (2009) The cobinamide amidohydrolase (cobyric acid-forming) CbiZ enzyme: a critical activity of the cobamide remodelling system of Rhodobacter sphaeroides. Mol Microbiol 74(5):1198–1210. doi: 10.1111/j.1365-2958.2009.06928.x PubMedPubMedCentralCrossRefGoogle Scholar
  38. Gribble GW (1998) Naturally occurring organohalogen compounds. Acc Chem Res 31(3):141–152CrossRefGoogle Scholar
  39. Grostern A, Edwards EA (2009) Characterization of a Dehalobacter coculture that dechlorinates 1,2-dichloroethane to ethene and identification of the putative reductive dehalogenase gene. Appl Environ Microbiol 75(9):2684–2693. doi: 10.1128/AEM.02037-08 PubMedPubMedCentralCrossRefGoogle Scholar
  40. Horwich AL, Fenton WA, Chapman E, Farr GW (2007) Two families of chaperonin: Physiology and mechanism. Annu Rev Cell Dev Biol 23:115–145PubMedCrossRefGoogle Scholar
  41. Hug LA, Salehi M, Nuin P, Tillier ER, Edwards EA (2011) Design and verification of a pangenome microarray oligonucleotide probe set for Dehalococcoides spp. Appl Environ Microbiol 77(15):5361–5369. doi: 10.1128/AEM.00063-11 PubMedPubMedCentralCrossRefGoogle Scholar
  42. Hug LA, Maphosa F, Leys D, Löffler FE, Smidt H, Edwards EA, Adrian L (2013) Overview of organohalide-respiring bacteria and a proposal for a classification system for reductive dehalogenases. Philos Trans R Soc Lond B Biol Sci 368(1616):20120322. doi: 10.1098/rstb.2012.0322 PubMedPubMedCentralCrossRefGoogle Scholar
  43. Islam MA, Waller AS, Hug LA, Provart NJ, Edwards EA, Mahadevan R (2014) New insights into Dehalococcoides mccartyi metabolism from a reconstructed metabolic network-based systems-level analysis of D. mccartyi transcriptomes. PLoS ONE 9(4):e94808. doi: 10.1371/journal.pone.0094808 PubMedPubMedCentralCrossRefGoogle Scholar
  44. John M, Rubick R, Schmitz RP, Rakoczy J, Schubert T, Diekert G (2009) Retentive memory of bacteria: long-term regulation of dehalorespiration in Sulfurospirillum multivorans. J Bacteriol 191(5):1650–1655. doi: 10.1128/JB.00597-08 PubMedCrossRefGoogle Scholar
  45. Johnson DR, Lee PK, Holmes VF, Fortin AC, Alvarez-Cohen L (2005) Transcriptional expression of the tceA gene in a Dehalococcoides-containing microbial enrichment. Appl Environ Microbiol 71(11):7145–7151. doi: 10.1128/AEM.71.11.7145-7151.2005 PubMedPubMedCentralCrossRefGoogle Scholar
  46. Johnson DR, Brodie EL, Hubbard AE, Andersen GL, Zinder SH, Alvarez-Cohen L (2008) Temporal transcriptomic microarray analysis of “Dehalococcoides ethenogenes” strain 195 during the transition into stationary phase. Appl Environ Microbiol 74(9):2864–2872PubMedPubMedCentralCrossRefGoogle Scholar
  47. Johnson DR, Nemir A, Andersen GL, Zinder SH, Alvarez-Cohen L (2009) Transcriptomic microarray analysis of corrinoid responsive genes in Dehalococcoides ethenogenes strain 195. FEMS Microbiol Lett 294(2):198–206PubMedCrossRefGoogle Scholar
  48. Joyce MG, Levy C, Gábor K, Pop SM, Biehl BD, Doukov TI, Ryter JM, Mazon H, Smidt H, van den Heuvel RH, Ragsdale SW, van der Oost J, Leys D (2006) CprK crystal structures reveal mechanism for transcriptional control of halorespiration. J Biol Chem 281(38):28318–28325. doi: 10.1074/jbc.M602654200 PubMedCrossRefGoogle Scholar
  49. Justicia-Leon SD, Ritalahti KM, Mack EE, Löffler FE (2012) Dichloromethane fermentation by a Dehalobacter sp. in an enrichment culture derived from pristine river sediment. Appl Environ Microbiol 78(4):1288–1291. doi: 10.1128/AEM.07325-11 PubMedPubMedCentralCrossRefGoogle Scholar
  50. Keller S, Ruetz M, Kunze C, Kräutler B, Diekert G, Schubert T (2013) Exogenous 5,6-dimethylbenzimidazole caused production of a non-functional tetrachloroethene reductive dehalogenase in Sulfurospirillum multivorans. Environ Microbiol 16(11):3361–3369. doi: 10.1111/1462-2920.12268 PubMedCrossRefGoogle Scholar
  51. Kemp LR, Dunstan MS, Fisher K, Warwicker J, Leys D (2013) The transcriptional regulator CprK detects chlorination by combining direct and indirect readout mechanisms. Philos Trans R Soc Lond B Biol Sci 368(1616):20120323. doi: 10.1098/rstb.2012.0323 PubMedPubMedCentralCrossRefGoogle Scholar
  52. Kim S-H, Harzman C, Davis J, Hutcheson R, Broderick J, Marsh T, Tiedje J (2012) Genome sequence of Desulfitobacterium hafniense DCB-2, a Gram-positive anaerobe capable of dehalogenation and metal reduction. BMC Microbiol 12(1):21. doi: 10.1186/1471-2180-12-21 PubMedPubMedCentralCrossRefGoogle Scholar
  53. Kim YE, Hipp MS, Bracher A, Hayer-Hartl M, Ulrich Hartl F (2013) Molecular chaperone functions in protein folding and proteostasis. Annu Rev Biochem 82:323–355PubMedCrossRefGoogle Scholar
  54. Körner H, Sofia HJ, Zumft WG (2003) Phylogeny of the bacterial superfamily of Crp-Fnr transcription regulators: exploiting the metabolic spectrum by controlling alternative gene programs. FEMS Microbiol Rev 27(5):559–592PubMedCrossRefGoogle Scholar
  55. Krajmalnik-Brown R, Hölscher T, Thomson IN, Saunders FM, Ritalahti KM, Löffler FE (2004) Genetic identification of a putative vinyl chloride reductase in Dehalococcoides sp. strain BAV1. Appl Environ Microbiol 70(10):6347–6351. doi: 10.1128/AEM.70.10.6347-6351.2004 PubMedPubMedCentralCrossRefGoogle Scholar
  56. Kranzioch I, Ganz S, Tiehm A (2014) Chloroethene degradation and expression of Dehalococcoides dehalogenase genes in cultures originating from Yangtze sediments. Environ Sci Pollut Res Int 20(10):7046–7056. doi: 10.1007/s11356-014-3574-4 CrossRefGoogle Scholar
  57. Kräutler B, Fieber W, Ostermann S, Fasching M, Ongania KH, Gruber K, Kratky C, Mikl C (2003) The cofactor of tetrachloroethene reductive dehalogenase of Dehalospirillum multivorans is norpseudo-B-12, a new type of a natural corrinoid. Helv Chim Acta 86(11):3698–3716CrossRefGoogle Scholar
  58. Kruse T, Maillard J, Holliger C, Goodwin L, Woyke T, Teshima H, Bruce D, Detter C, Tapia R, Han C, Huntemann M, Wei C-L, Han J, Chen A, Kyrpides N, Szeto E, Markowitz V, Ivanova N, Pagani I, Pati A, Pitluck S, Nolan M, Holliger C, Smidt H (2013) Complete genome sequence of Dehalobacter restrictus PER-K23. Stand Genomic Sci 8(3):375–388PubMedPubMedCentralCrossRefGoogle Scholar
  59. Kruse T, van de Pas BA, Atteia A, Krab K, Hagen WR, Goodwin L, Chain P, Boeren S, Maphosa F, Schraa G, de Vos WM, van der Oost J, Smidt H, Stams AJ (2015) Genomic, proteomic and biochemical analysis of the organohalide respiratory pathway in Desulfitobacterium dehalogenans. J Bacteriol 197(5):893–904. doi: 10.1128/JB.02370-14 PubMedCrossRefGoogle Scholar
  60. Kube M, Beck A, Zinder SH, Kuhl H, Reinhardt R, Adrian L (2005) Genome sequence of the chlorinated compound-respiring bacterium Dehalococcoides species strain CBDB1. Nat Biotechnol 23(10):1269–1273. doi: 10.1038/nbt1131 PubMedCrossRefGoogle Scholar
  61. Lee PK, Johnson DR, Holmes VF, He J, Alvarez-Cohen L (2006) Reductive dehalogenase gene expression as a biomarker for physiological activity of Dehalococcoides spp. Appl Environ Microbiol 72(9):6161–6168. doi: 10.1128/AEM.01070-06 PubMedPubMedCentralCrossRefGoogle Scholar
  62. Lee PK, Macbeth TW, Sorenson KS Jr, Deeb RA, Alvarez-Cohen L (2008) Quantifying genes and transcripts to assess the in situ physiology of “Dehalococcoides” spp. in a trichloroethene-contaminated groundwater site. Appl Environ Microbiol 74(9):2728–2739. doi: 10.1128/AEM.02199-07 PubMedPubMedCentralCrossRefGoogle Scholar
  63. Lee PKH, Cheng D, Hu P, West KA, Dick GJ, Brodie EL, Andersen GL, Zinder SH, He J, Alvarez-Cohen L (2011) Comparative genomics of two newly isolated Dehalococcoides strains and an enrichment using a genus microarray. ISME J 5(6):1014–1024. doi: 10.1038/ismej.2010.202 PubMedPubMedCentralCrossRefGoogle Scholar
  64. Lee M, Low A, Zemb O, Koenig J, Michaelsen A, Manefield M (2012a) Complete chloroform dechlorination by organochlorine respiration and fermentation. Environ Microbiol 14(4):883–894. doi: 10.1111/j.1462-2920.2011.02656.x PubMedCrossRefGoogle Scholar
  65. Lee PK, Dill BD, Louie TS, Shah M, Verberkmoes NC, Andersen GL, Zinder SH, Alvarez-Cohen L (2012b) Global transcriptomic and proteomic responses of Dehalococcoides ethenogenes strain 195 to fixed nitrogen limitation. Appl Environ Microbiol 78(5):1424–1436. doi: 10.1128/AEM.06792-11 PubMedPubMedCentralCrossRefGoogle Scholar
  66. Levy C, Pike K, Heyes DJ, Joyce MG, Gábor K, Smidt H, van der Oost J, Leys D (2008) Molecular basis of halorespiration control by CprK, a CRP-FNR type transcriptional regulator. Mol Microbiol 70(1):151–167. doi: 10.1111/j.1365-2958.2008.06399.x PubMedPubMedCentralCrossRefGoogle Scholar
  67. Löffler FE, Yan J, Ritalahti KM, Adrian L, Edwards EA, Konstantinidis KT, Müller JA, Fullerton H, Zinder SH, Spormann AM (2013) Dehalococcoides mccartyi gen. nov., sp. nov., obligately organohalide-respiring anaerobic bacteria relevant to halogen cycling and bioremediation, belong to a novel bacterial class, Dehalococcoidia classis nov., order Dehalococcoidales ord. nov. and family Dehalococcoidaceae fam. nov., within the phylum Chloroflexi. Int J Syst Evol Microbiol 63(PART2):625–635PubMedCrossRefGoogle Scholar
  68. Lohner ST, Spormann AM (2013) Identification of a reductive tetrachloroethene dehalogenase in Shewanella sediminis. Philos Trans R Soc Lond B Biol Sci 368(1616):20120326. doi: 10.1098/rstb.2012.0326 PubMedPubMedCentralCrossRefGoogle Scholar
  69. Lund PA (2009) Multiple chaperonins in bacteria—why so many? FEMS Microbiol Rev 33(4):785–800PubMedCrossRefGoogle Scholar
  70. Mac Nelly A, Kai M, Svatoš A, Diekert G, Schubert T (2014) Functional heterologous production of reductive dehalogenases from Desulfitobacterium hafniense strains. Appl Environ Microbiol 80(14):4313–4322. doi: 10.1128/aem.00881-14 PubMedPubMedCentralCrossRefGoogle Scholar
  71. Magnuson JK, Romine MF, Burris DR, Kingsley MT (2000) Trichloroethene reductive dehalogenase from Dehalococcoides ethenogenes: sequence of tceA and substrate range characterization. Appl Environ Microbiol 66(12):5141–5147PubMedPubMedCentralCrossRefGoogle Scholar
  72. Maillard J, Regeard C, Holliger C (2005) Isolation and characterization of Tn-Dha1, a transposon containing the tetrachloroethene reductive dehalogenase of Desulfitobacterium hafniense strain TCE1. Environ Microbiol 7(1):107–117PubMedCrossRefGoogle Scholar
  73. Maillard J, Genevaux P, Holliger C (2011) Redundancy and specificity of multiple trigger factor chaperones in Desulfitobacteria. Microbiology 157(8):2410–2421PubMedCrossRefGoogle Scholar
  74. Mansfeldt CB, Rowe AR, Heavner GL, Zinder SH, Richardson RE (2014) Meta-analyses of Dehalococcoides mccartyi strain 195 transcriptomic profiles identify a respiration rate-related gene expression transition point and interoperon recruitment of a key oxidoreductase subunit. Appl Environ Microbiol 80(19):6062–6072. doi: 10.1128/AEM.02130-14 PubMedPubMedCentralCrossRefGoogle Scholar
  75. Maphosa F (2010) Chasing organohalide respirers: ecogenomics approaches to assess the bioremediation capacity of soils. PhD thesis, Wageningen University, WageningenGoogle Scholar
  76. Maphosa F, Van Passel MWJ, De Vos WM, Smidt H (2012) Metagenome analysis reveals yet unexplored reductive dechlorinating potential of Dehalobacter sp. E1 growing in co-culture with Sedimentibacter sp. Environ Microbiol Rep 4(6):604–616. doi: 10.1111/j.1758-2229.2012.00376.x
  77. Mascher T, Helmann JD, Unden G (2006) Stimulus perception in bacterial signal-transducing histidine kinases. Microbiol Mol Biol Rev 70(4):910–938PubMedPubMedCentralCrossRefGoogle Scholar
  78. Mazon H, Gábor K, Leys D, Heck AJ, van der Oost J, van den Heuvel RH (2007) Transcriptional activation by CprK1 is regulated by protein structural changes induced by effector binding and redox state. J Biol Chem 282(15):11281–11290. doi: 10.1074/jbc.M611177200 PubMedCrossRefGoogle Scholar
  79. McMurdie PJ, Behrens SF, Müller JA, Goke J, Ritalahti KM, Wagner R, Goltsman E, Lapidus A, Holmes S, Löffler FE, Spormann AM (2009) Localized plasticity in the streamlined genomes of vinyl chloride respiring Dehalococcoides. PLoS Genet 5(11):e1000714. doi: 10.1371/journal.pgen.1000714 PubMedPubMedCentralCrossRefGoogle Scholar
  80. McMurdie PJ, Hug LA, Edwards EA, Holmes S, Spormann AM (2011) Site-specific mobilization of vinyl chloride respiration islands by a mechanism common in Dehalococcoides. BMC Genomics 12:287. doi: 10.1186/1471-2164-12-287 PubMedPubMedCentralCrossRefGoogle Scholar
  81. Men Y, Feil H, Verberkmoes NC, Shah MB, Johnson DR, Lee PK, West KA, Zinder SH, Andersen GL, Alvarez-Cohen L (2012) Sustainable syntrophic growth of Dehalococcoides ethenogenes strain 195 with Desulfovibrio vulgaris Hildenborough and Methanobacterium congolense: global transcriptomic and proteomic analyses. ISME J 6(2):410–421. doi: 10.1038/ismej.2011.111 PubMedCrossRefGoogle Scholar
  82. Men Y, Lee PKH, Harding KC, Alvarez-Cohen L (2013) Characterization of four TCE-dechlorinating microbial enrichments grown with different cobalamin stress and methanogenic conditions. Appl Microbiol Biotechnol 97(14):6439–6450PubMedCrossRefGoogle Scholar
  83. Men Y, Seth EC, Yi S, Allen RH, Taga ME, Alvarez-Cohen L (2014) Sustainable growth of Dehalococcoides mccartyi 195 by corrinoid salvaging and remodeling in defined lactate-fermenting consortia. Appl Environ Microbiol 80(7):2133–2141PubMedPubMedCentralCrossRefGoogle Scholar
  84. Moore SJ, Lawrence AD, Biedendieck R, Deery E, Frank S, Howard MJ, Rigby SEJ, Warren MJ (2013) Elucidation of the anaerobic pathway for the corrin component of cobalamin (vitamin B12). Proc Natl Acad Sci USA 110(37):14906–14911. doi: 10.1073/pnas.1308098110 PubMedPubMedCentralCrossRefGoogle Scholar
  85. Morita Y, Futagami T, Goto M, Furukawa K (2009) Functional characterization of the trigger factor protein PceT of tetrachloroethene-dechlorinating Desulfitobacterium hafniense Y51. Appl Microbiol Biotechnol 83(4):775–781PubMedCrossRefGoogle Scholar
  86. Mukherjee K, Bowman KS, Rainey FA, Siddaramappa S, Challacombe JF, Moe WM (2014) Dehalogenimonas lykanthroporepellens BL-DC-9T simultaneously transcribes many rdhA genes during organohalide respiration with 1,2-DCA, 1,2-DCP, and 1,2,3-TCP as electron acceptors. FEMS Microbiol Lett 354(2):111–118. doi: 10.1111/1574-6968.12434 PubMedCrossRefGoogle Scholar
  87. Neumann A, Wohlfarth G, Diekert G (1998) Tetrachloroethene dehalogenase from Dehalospirillum multivorans: cloning, sequencing of the encoding genes, and expression of the pceA gene in Escherichia coli. J Bacteriol 180(16):4140–4145PubMedPubMedCentralGoogle Scholar
  88. Nonaka H, Keresztes G, Shinoda Y, Ikenaga Y, Abe M, Naito K, Inatomi K, Furukawa K, Inui M, Yukawa H (2006) Complete genome sequence of the dehalorespiring bacterium Desulfitobacterium hafniense Y51 and comparison with Dehalococcoides ethenogenes 195. J Bacteriol 188(6):2262–2274PubMedPubMedCentralCrossRefGoogle Scholar
  89. Padilla-Crespo E, Yan J, Swift C, Wagner DD, Chourey K, Hettich RL, Ritalahti KM, Löffler FE (2014) Identification and environmental distribution of dcpA, which encodes the reductive dehalogenase catalyzing the dichloroelimination of 1,2-dichloropropane to propene in organohalide-respiring Chloroflexi. Appl Environ Microbiol 80(3):808–818. doi: 10.1128/AEM.02927-13 PubMedPubMedCentralCrossRefGoogle Scholar
  90. Pagani I, Liolios K, Jansson J, Chen IMA, Smirnova T, Nosrat B, Markowitz VM, Kyrpides NC (2012) The Genomes OnLine Database (GOLD) v. 4: status of genomic and metagenomic projects and their associated metadata. Nucleic Acids Res 40(D1):D571–D579PubMedCrossRefGoogle Scholar
  91. Palmer T, Berks BC (2012) The twin-arginine translocation (Tat) protein export pathway. Nature Rev Microbiol 10(7):483–496Google Scholar
  92. Peng X, Yamamoto S, Vertes AA, Keresztes G, Inatomi K, Inui M, Yukawa H (2012) Global transcriptome analysis of the tetrachloroethene-dechlorinating bacterium Desulfitobacterium hafniense Y51 in the presence of various electron donors and terminal electron acceptors. J Ind Microbiol Biotechnol 39(2):255–268. doi: 10.1007/s10295-011-1023-7 PubMedCrossRefGoogle Scholar
  93. Pop SM, Kolarik RJ, Ragsdale SW (2004) Regulation of anaerobic dehalorespiration by the transcriptional activator CprK. J Biol Chem 279(48):49910–49918. doi: 10.1074/jbc.M409435200 PubMedCrossRefGoogle Scholar
  94. Pöritz M, Goris T, Wubet T, Tarkka MT, Buscot F, Nijenhuis I, Lechner U, Adrian L (2013) Genome sequences of two dehalogenation specialists—Dehalococcoides mccartyi strains BTF08 and DCMB5 enriched from the highly polluted Bitterfeld region. FEMS Microbiol Lett 343(2):101–104. doi: 10.1111/1574-6968.12160 PubMedCrossRefGoogle Scholar
  95. Prat L (2009) Identification and characterization of proteins supporting dehalorespiration in Desulfitobacterium hafniense strain TCE1. Ph.D. thesis, École Polytechnique Fédérale de Lausanne, LausanneGoogle Scholar
  96. Prat L, Maillard J, Grimaud R, Holliger C (2011) Physiological adaptation of Desulfitobacterium hafniense strain TCE1 to tetrachloroethene respiration. Appl Environ Microbiol 77(11):3853–3859PubMedPubMedCentralCrossRefGoogle Scholar
  97. Rahm BG, Richardson RE (2008) Correlation of respiratory gene expression levels and pseudo-steady-state PCE respiration rates in Dehalococcoides ethenogenes. Environ Sci Technol 42(2):416–421PubMedCrossRefGoogle Scholar
  98. Rahm BG, Morris RM, Richardson RE (2006) Temporal expression of respiratory genes in an enrichment culture containing Dehalococcoides ethenogenes. Appl Environ Microbiol 72(8):5486–5491. doi: 10.1128/AEM.00855-06 PubMedPubMedCentralCrossRefGoogle Scholar
  99. Regeard C, Maillard J, Dufraigne C, Deschavanne P, Holliger C (2005) Indications for acquisition of reductive dehalogenase genes through horizontal gene transfer by Dehalococcoides ethenogenes strain 195. Appl Environ Microbiol 71(6):2955–2961PubMedPubMedCentralCrossRefGoogle Scholar
  100. Reinhold A, Westermann M, Seifert J, von Bergen M, Schubert T, Diekert G (2012) Impact of Vitamin B12 on formation of the tetrachloroethene reductive dehalogenase in Desulfitobacterium hafniense strain Y51. Appl Environ Microbiol 78(22):8025–8032PubMedPubMedCentralCrossRefGoogle Scholar
  101. Rowe AR, Heavner GL, Mansfeldt CB, Werner JJ, Richardson RE (2012) Relating chloroethene respiration rates in Dehalococcoides to protein and mRNA biomarkers. Environ Sci Technol 46(17):9388–9397. doi: 10.1021/es300996c PubMedCrossRefGoogle Scholar
  102. Rowe AR, Mansfeldt CB, Heavner GL, Richardson RE (2015) Relating mRNA and protein biomarker levels in a Dehalococcoides and Methanospirillum-containing community. Appl Microbiol Biotechnol 99(5):2313–2327. doi: 10.1007/s00253-014-6220-7 PubMedCrossRefGoogle Scholar
  103. Rupakula A, Kruse T, Boeren S, Holliger C, Smidt H, Maillard J (2013) The restricted metabolism of the obligate organohalide respiring bacterium Dehalobacter restrictus: lessons from tiered functional genomics. Philos Trans R Soc Lond B Biol Sci 368(1616):20120325. doi: 10.1098/rstb.2012.0325 PubMedPubMedCentralCrossRefGoogle Scholar
  104. Rupakula A, Lu Y, Kruse T, Boeren S, Holliger C, Smidt H, Maillard J (2015) Functional genomics of corrinoid starvation in the organohalide-respiring bacterium Dehalobacter restrictus strain PER-K23. Front Microbiol 5:751. doi: 10.3389/fmicb.2014.00751 PubMedPubMedCentralCrossRefGoogle Scholar
  105. Saunders NFW, Houben ENG, Koefoed S, De Weert S, Reijnders WNM, Westerhoff HV, De Boer APN, Van Spanning RJM (1999) Transcription regulation of the nir gene cluster encoding nitrite reductase of Paracoccus denitrificans involves NNR and NirI, a novel type of membrane protein. Mol Microbiol 34(1):24–36PubMedCrossRefGoogle Scholar
  106. Seshadri R, Adrian L, Fouts DE, Eisen JA, Phillippy AM, Methe BA, Ward NL, Nelson WC, Deboy RT, Khouri HM, Kolonay JF, Dodson RJ, Daugherty SC, Brinkac LM, Sullivan SA, Madupu R, Nelson KT, Kang KH, Impraim M, Tran K, Robinson JM, Forberger HA, Fraser CM, Zinder SH, Heidelberg JF (2005) Genome sequence of the PCE-dechlorinating bacterium Dehalococcoides ethenogenes. Science 307(5706):105–108PubMedCrossRefGoogle Scholar
  107. Siddaramappa S, Challacombe JF, Delano SF, Green LD, Daligault H, Bruce D, Detter C, Tapia R, Han S, Goodwin L, Han J, Woyke T, Pitluck S, Pennacchio L, Nolan M, Land M, Chang YJ, Kyrpides NC, Ovchinnikova G, Hauser L, Lapidus A, Yan J, Bowman KS, da Costa MS, Rainey FA, Moe WM (2012) Complete genome sequence of Dehalogenimonas lykanthroporepellens type strain (BL-DC-9T) and comparison to “Dehalococcoides” strains. Stand Genomic Sci 6(2):251–264. doi: 10.4056/sigs.2806097 PubMedPubMedCentralCrossRefGoogle Scholar
  108. Simon J, Klotz MG (2013) Diversity and evolution of bioenergetic systems involved in microbial nitrogen compound transformations. Biochim Biophys Acta 1827(2):114–135. doi: 10.1016/j.bbabio.2012.07.005 PubMedCrossRefGoogle Scholar
  109. Smidt H, van Leest M, van der Oost J, de Vos WM (2000) Transcriptional regulation of the cpr gene cluster in ortho-chlorophenol-respiring Desulfitobacterium dehalogenans. J Bacteriol 182(20):5683–5691PubMedPubMedCentralCrossRefGoogle Scholar
  110. Suyama A, Yamashita M, Yoshino S, Furukawa K (2002) Molecular characterization of the PceA reductive dehalogenase of Desulfitobacterium sp. strain Y51. J Bacteriol 184(13):3419–3425PubMedPubMedCentralCrossRefGoogle Scholar
  111. Suzuki D, Irieda H, Homma M, Kawagishi I, Sudo Y (2010) Phototactic and chemotactic signal transduction by transmembrane receptors and transducers in microorganisms. Sensors 10(4):4010–4039PubMedPubMedCentralCrossRefGoogle Scholar
  112. Tang YJ, Yi S, Zhuang W-Q, Zinder SH, Keasling JD, Alvarez-Cohen L (2009) Investigation of carbon metabolism in “Dehalococcoides ethenogenes” strain 195 by use of isotopomer and transcriptomic analyses. J Bacteriol 191(16):5224–5231PubMedPubMedCentralCrossRefGoogle Scholar
  113. Tang S, Gong Y, Edwards EA (2012) Semi-automatic in silico gap closure enabled de novo assembly of two Dehalobacter genomes from metagenomic data. PLoS ONE 7(12):e52038PubMedPubMedCentralCrossRefGoogle Scholar
  114. Thibodeau J, Gauthier A, Duguay M, Villemur R, Lépine F, Juteau P, Beaudet R (2004) Purification, cloning, and sequencing of a 3,5-dichlorophenol reductive dehalogenase from Desulfitobacterium frappieri PCP-1. Appl Environ Microbiol 70(8):4532–4537. doi: 10.1128/AEM.70.8.4532-4537.2004 PubMedPubMedCentralCrossRefGoogle Scholar
  115. Thirumalai D, Lorimer GH (2001) Chaperonin-mediated protein folding. Annu Rev Biophys Biomol Struct 30:245–269PubMedCrossRefGoogle Scholar
  116. Thomas SH, Wagner RD, Arakaki AK, Skolnick J, Kirby JR, Shimkets LJ, Sanford RA, Löffler FE (2008) The mosaic genome of Anaeromyxobacter dehalogenans strain 2CP-C suggests an aerobic common ancestor to the delta-proteobacteria. PLoS ONE 3(5):e2103. doi: 10.1371/journal.pone.0002103 PubMedPubMedCentralCrossRefGoogle Scholar
  117. Trzebiatowski JR, O’Toole GA, Escalante-Semerena JC (1994) The cobT gene of Salmonella typhimurium encodes the NaMN: 5,6-dimethylbenzimidazole phosphoribosyltransferase responsible for the synthesis of N1-(5-phospho-α-D-ribosyl)-5,6-dimethylbenzimidazole, an intermediate in the synthesis of the nucleotide loop of cobalamin. J Bacteriol 176(12):3568–3575PubMedPubMedCentralGoogle Scholar
  118. van de Pas BA, Smidt H, Hagen WR, van der Oost J, Schraa G, Stams AJ, de Vos WM (1999) Purification and molecular characterization of ortho-chlorophenol reductive dehalogenase, a key enzyme of halorespiration in Desulfitobacterium dehalogenans. J Biol Chem 274(29):20287–22092PubMedCrossRefGoogle Scholar
  119. Villemur R, Saucier M, Gauthier A, Beaudet R (2002) Occurrence of several genes encoding putative reductive dehalogenases in Desulfitobacterium hafniense/frappieri and Dehalococcoides ethenogenes. Can J Microbiol 48(8):697–706PubMedCrossRefGoogle Scholar
  120. Villemur R, Lanthier M, Beaudet R, Lepine F (2006) The Desulfitobacterium genus. FEMS Microbiol Rev 30(5):706–733PubMedCrossRefGoogle Scholar
  121. Wadhams GH, Armitage JP (2004) Making sense of it all: bacterial chemotaxis. Nature Rev Mol Cell Biol 5(12):1024–1037CrossRefGoogle Scholar
  122. Wagner A, Adrian L, Kleinsteuber S, Andreesen JR, Lechner U (2009) Transcription analysis of genes encoding homologues of reductive dehalogenases in “Dehalococcoides” sp. strain CBDB1 by using terminal restriction fragment length polymorphism and quantitative PCR. Appl Environ Microbiol 75(7):1876–1884PubMedPubMedCentralCrossRefGoogle Scholar
  123. Wagner DD, Hug LA, Hatt JK, Spitzmiller MR, Padilla-Crespo E, Ritalahti KM, Edwards EA, Konstantinidis KT, Löffler FE (2012) Genomic determinants of organohalide-respiration in Geobacter lovleyi, an unusual member of the Geobacteraceae. BMC Genomics 13(1):200. doi: 10.1186/1471-2164-13-200 PubMedPubMedCentralCrossRefGoogle Scholar
  124. Wagner A, Segler L, Kleinsteuber S, Sawers G, Smidt H, Lechner U (2013) Regulation of reductive dehalogenase gene transcription in Dehalococcoides mccartyi. Philos Trans R Soc Lond B Biol Sci 368(1616):20120317. doi: 10.1098/rstb.2012.0317 PubMedPubMedCentralCrossRefGoogle Scholar
  125. Waller AS, Krajmalnik-Brown R, Löffler FE, Edwards EA (2005) Multiple reductive-dehalogenase-homologous genes are simultaneously transcribed during dechlorination by Dehalococcoides-containing cultures. Appl Environ Microbiol 71(12):8257–8264. doi: 10.1128/Aem.71.12.8257-8264.2005 PubMedPubMedCentralCrossRefGoogle Scholar
  126. Waller AS, Hug LA, Mo K, Radford DR, Maxwell KL, Edwards EA (2012) Transcriptional analysis of a Dehalococcoides-containing microbial consortium reveals prophage activation. Appl Environ Microbiol 78(4):1178–1186. doi: 10.1128/AEM.06416-11 PubMedPubMedCentralCrossRefGoogle Scholar
  127. Wang S, Chng KR, Wilm A, Zhao S, Yang KL, Nagarajan N, He J (2014a) Genomic characterization of three unique Dehalococcoides that respire on persistent polychlorinated biphenyls. Proc Natl Acad Sci USA 111(33):12103–12108PubMedPubMedCentralCrossRefGoogle Scholar
  128. Wang S, Chng KR, Wu C, Wilm A, Nagarajan N, He J (2014b) Draft genome sequence of polychlorinated biphenyl-dechlorinating Dehalococcoides mccartyi strain SG1, which carries a circular putative plasmid. Genome Announc 2(5):e00901–e00914. doi: 10.1128/genomeA.00901-14 PubMedPubMedCentralGoogle Scholar
  129. West KA, Johnson DR, Hu P, DeSantis TZ, Brodie EL, Lee PK, Feil H, Andersen GL, Zinder SH, Alvarez-Cohen L (2008) Comparative genomics of “Dehalococcoides ethenogenes” 195 and an enrichment culture containing unsequenced “Dehalococcoides” strains. Appl Environ Microbiol 74(11):3533–3540. doi: 10.1128/AEM.01835-07 PubMedPubMedCentralCrossRefGoogle Scholar
  130. West KA, Lee PK, Johnson DR, Zinder SH, Alvarez-Cohen L (2013) Global gene expression of Dehalococcoides within a robust dynamic TCE-dechlorinating community under conditions of periodic substrate supply. Biotechnol Bioeng 110(5):1333–1341. doi: 10.1002/bit.24819 PubMedCrossRefGoogle Scholar
  131. Wilkinson SP, Grove A (2006) Ligand-responsive transcriptional regulation by members of the MarR family of winged helix proteins. Curr Issues Mol Biol 8(1):51–62PubMedGoogle Scholar
  132. Woodson JD, Escalante-Semerena JC (2004) CbiZ, an amidohydrolase enzyme required for salvaging the coenzyme B12 precursor cobinamide in archaea. Proc Natl Acad Sci USA 101(10):3591–3596PubMedPubMedCentralCrossRefGoogle Scholar
  133. Wunsch P, Zumft WG (2005) Functional domains of NosR, a novel transmembrane iron-sulfur flavoprotein necessary for nitrous oxide respiration. J Bacteriol 187(6):1992–2001PubMedPubMedCentralCrossRefGoogle Scholar
  134. Yan J, Ritalahti KM, Wagner DD, Löffler FE (2012) Unexpected specificity of interspecies cobamide transfer from Geobacter spp. to organohalide-respiring Dehalococcoides mccartyi strains. Appl Environ Microbiol 78(18):6630–6636PubMedPubMedCentralCrossRefGoogle Scholar
  135. Yan J, Im J, Yang Y, Löffler FE (2013) Guided cobalamin biosynthesis supports Dehalococcoides mccartyi reductive dechlorination activity. Philos Trans R Soc Lond B Biol Sci 368(1616):20120321. doi: 10.1098/rstb.2012.0320 CrossRefGoogle Scholar
  136. Yi S, Seth EC, Men YJ, Stabler SP, Allen RH, Alvarez-Cohen L, Taga ME (2012) Versatility in corrinoid salvaging and remodeling pathways supports corrinoid-dependent metabolism in Dehalococcoides mccartyi. Appl Environ Microbiol 78(21):7745–7752PubMedPubMedCentralCrossRefGoogle Scholar
  137. Zhang Y, Rodionov D, Gelfand M, Gladyshev V (2009) Comparative genomic analyses of nickel, cobalt and vitamin B12 utilization. BMC Genomics 10(1):78PubMedPubMedCentralCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Laboratory of MicrobiologyWageningen UniversityWageningenThe Netherlands
  2. 2.Institute of Biology/MicrobiologyMartin Luther University Halle-WittenbergHalleGermany

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