Using genome comparisons of wild-type and resistant mutants of to help understand mechanisms of resistance to methane inhibitors Open Access

Abstract

Methane emissions from enteric fermentation in the ruminant digestive system generated by methanogenic archaea are a significant contributor to anthropogenic greenhouse gas emissions. Additionally, methane produced as an end-product of enteric fermentation is an energy loss from digested feed. To control the methane emissions from ruminants, extensive research in the last decades has been focused on developing viable enteric methane mitigation practices, particularly, using methanogen-specific inhibitors. We report here the utilization of two known inhibitors of methanogenic archaea, neomycin and chloroform, together with a recently identified inhibitor, echinomycin, to produce resistant mutants of S2 and S0001. Whole-genome sequencing at high coverage (> 100-fold) was performed subsequently to investigate the potential targets of these inhibitors at the genomic level. Upon analysis of the whole-genome sequencing data, we identified mutations in a number of genetic loci pointing to potential mechanisms of inhibitor action and their underlying mechanisms of resistance.

Loading

Article metrics loading...

/content/journal/acmi/10.1099/acmi.0.000244
2021-07-21
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/acmi/3/7/acmi000244.html?itemId=/content/journal/acmi/10.1099/acmi.0.000244&mimeType=html&fmt=ahah

References

  1. Duin EC, Wagner T, Shima S, Prakash D, Cronin B et al. Mode of action uncovered for the specific reduction of methane emissions from ruminants by the small molecule 3-nitrooxypropanol. P Natl Acad Sci USA 2016; 113:E3185-E
    [Google Scholar]
  2. Myhre G. Anthropogenic and natural radiative forcing. Stocker T. eds In Climate Change 2013: The Physical Science Basis. Contribution of Working Group I to the Fifth Assessment Report of the Intergovernmental Panel on Climate Change Cambridge, UK: Cambridge Univ Press; 2013 pp 659–740
    [Google Scholar]
  3. Gerber PJ, Henderson B, Makkar HPS. Mitigation of greenhouse gas emissions in livestock production – A review of technical options for non-CO2 emissions. In FAO Animal Production and Health Paper Vol NO.177 FAO, Roman, Italy: 2013
    [Google Scholar]
  4. Conrad R. The global methane cycle: recent advances in understanding the microbial processes involved. Environ Microbiol Rep 2009; 1:285–292 [View Article] [PubMed]
    [Google Scholar]
  5. Johnson KA, Johnson DE. Methane emissions from Cattle. J Anim Sci 1995; 73:2483–2492 [View Article] [PubMed]
    [Google Scholar]
  6. Van Nevel CJ, Demeyer DI. Control of rumen methanogenesis. Environ Monit Assess 1996; 42:73–97 [View Article] [PubMed]
    [Google Scholar]
  7. Henderson G, Cook GM, Ronimus RS. Enzyme- and gene-based approaches for developing methanogen-specific compounds to control ruminant methane emissions: A review. Anim Prod Sci 2016
    [Google Scholar]
  8. Hook SE, Wright ADG, McBride BW. Methanogens: Methane producers of the rumen and mitigation strategies. Archaea 2010; 2010:945785 [View Article]
    [Google Scholar]
  9. Buddle BM, Denis M, Attwood GT, Altermann E, Janssen PH et al. Strategies to reduce methane emissions from farmed ruminants grazing on pasture. Vet J 2011; 188:11–17 [View Article] [PubMed]
    [Google Scholar]
  10. Leahy SC, Kelly WJ, Altermann E, Ronimus RS, Yeoman CJ et al. The genome sequence of the rumen methanogen Methanobrevibacter ruminantium reveals new possibilities for controlling ruminant methane emissions. PloS one 2010; 5:e8926 [View Article] [PubMed]
    [Google Scholar]
  11. Sun XZ, Henderson G, Cox F, Molano G, Harrison SJ et al. Lambs fed fresh winter forage rape (Brassica napus L.) emit less methane than those fed perennial ryegrass (Lolium perenne L.), and possible mechanisms behind the difference. PloS one 2015; 10:
    [Google Scholar]
  12. Eckard RJ, Grainger C, de Klein CAM. Options for the abatement of methane and nitrous oxide from ruminant production: A review. Livest Sci 2010; 130:47–56 [View Article]
    [Google Scholar]
  13. Patra AK, Saxena J. A new perspective on the use of plant secondary metabolites to inhibit methanogenesis in the rumen. Phytochemistry 2010; 71:1198–1222 [View Article] [PubMed]
    [Google Scholar]
  14. Hegarty RS. Reducing rumen methane emissions through elimination of rumen protozoa. Aust J Agr Res 1999; 50:1321–1327
    [Google Scholar]
  15. Wedlock DN, Pedersen G, Denis M, Dey D, Janssen PH et al. Development of a vaccine to mitigate greenhouse gas emissions in agriculture: Vaccination of sheep with methanogen fractions induces antibodies that block methane production in vitro. New Zeal Vet J 2010; 58:29–36
    [Google Scholar]
  16. Chalupa W. Chemical control of rumen microbial metabolism. Ruckebusch Y, Thivend P. eds In Digestive Physiology and Metabolism in Ruminants: Proceedings of the 5th International Symposium on Ruminant Physiology, Held at Clermont – Ferrand, on 3rd–7th September, 1979 Dordrecht: Springer Netherlands; 1980 pp 325–347
    [Google Scholar]
  17. Trei JE, Scott GC, Parish RC. Influence of Methane Inhibition on energetic efficiency of lambs. J Anim Sci 1972; 34:510–517 [View Article] [PubMed]
    [Google Scholar]
  18. Immig I, Demeyer D, Fiedler D, Van Nevel C, Mbanzamihigo L. Attempts to induce reductive acetogenesis into a sheep rumen. Arch Tierernahr 1996; 49:363–370 [View Article]
    [Google Scholar]
  19. Denman SE, Martinez Fernandez G, Shinkai T, Mitsumori M, McSweeney CS. Metagenomic analysis of the rumen microbial community following inhibition of methane formation by a halogenated methane analog. Front Microbiol 2015; 6:1087 [View Article]
    [Google Scholar]
  20. Knight T, Ronimus RS, Dey D, Tootill C, Naylor G et al. Chloroform decreases rumen methanogenesis and methanogen populations without altering rumen function in cattle. Animal Feed Science and Technology 2011 166–167 101–112 [View Article]
    [Google Scholar]
  21. Garcia-Lopez PM, Kung L, Odom JM. In vitro inhibition of microbial methane production by 9,10-anthraquinone. J Anim Sci 1996; 74:2276–2284 [View Article] [PubMed]
    [Google Scholar]
  22. Soliva CR, Amelchanka SL, Duval SM, Kreuzer M. Ruminal methane inhibition potential of various pure compounds in comparison with garlic oil as determined with a rumen simulation technique (Rusitec. Br J Nutr 2011; 106:114–122 [View Article] [PubMed]
    [Google Scholar]
  23. Hristov AN, Oh J, Giallongo F, Frederick TW, Harper MT et al. An inhibitor persistently decreased enteric methane emission from dairy cows with no negative effect on milk production (vol 112, pg 10663, 2015. P Natl Acad Sci USA 2015; 112:E5218-E
    [Google Scholar]
  24. Farley KR, Metcalf WW. 2019) The streptothricin acetyltransferase (sat) gene as a positive selectable marker for methanogenic archaea. FEMS Microbiol Lett 2019; 366:fnz216 [View Article] [PubMed]
    [Google Scholar]
  25. Jasso-Chávez R, Lira-Silva E, González-Sánchez K, Larios-Serrato V, Mendoza-Monzoy DL et al. 2019) Marine Archaeon Methanosarcina acetivorans enhances polyphosphate metabolism under persistent cadmium stress. Front Microbiol 2019; 10:2432 [View Article] [PubMed]
    [Google Scholar]
  26. Gilbert DE, Vandermarel GA, Vanboom JH, Feigon J. Unstable Hoogsteen base-pairs adjacent to Echinomycin binding-sites within a DNA duplex. P Natl Acad Sci USA 1989; 86:3006–3010
    [Google Scholar]
  27. Dell A, Williams DH, Morris HR, Smith GA, Feeney J et al. Structure revision of the antibiotic echinomycin. J Am Chem Soc 1975; 97:2497–2502 [View Article] [PubMed]
    [Google Scholar]
  28. Kim JB, Lee GS, Kim YB, Kim SK, Kim YH. In vitro antibacterial activity of echinomycin and a novel analogue, YK2000, against vancomycin-resistant enterococci. Int J Antimicrob Ag 2004; 24:613–615
    [Google Scholar]
  29. Kong DH, Park EJ, Stephen AG, Calvani M, Cardellina JH et al. Echinomycin, a small-molecule inhibitor of hypoxia-inducible factor-1 DNA-binding activity. Cancer Res 2005; 65:9047–9055 [View Article] [PubMed]
    [Google Scholar]
  30. Jayasuriya H, Zink DL, Polishook JD, Bills GF, Dombrowski AW et al. Identification of diverse microbial metabolites as potent inhibitors of HIV-1 tat transactivation. Chem Biodivers 2005; 2:112–122 [View Article] [PubMed]
    [Google Scholar]
  31. Lee YK, Park JH, Moon HT, Lee DY, Yun JH et al. The short-term effects on restenosis and thrombosis of echinomycin-eluting stents topcoated with a hydrophobic heparin-containing polymer. Biomaterials 2007; 28:1523–1530
    [Google Scholar]
  32. Park YS, Shin WS, Kim SK. In vitro and in vivo activities of echinomycin against clinical isolates of Staphylococcus aureus. J Antimicrob Chemoth 2008; 61:163–168
    [Google Scholar]
  33. Weimar MR, Cheung J, Dey D, McSweeney C, Morrison M et al. Development of multiwell-plate methods using pure cultures of methanogens to identify new inhibitors for suppressing ruminant methane emissions. Appl Environ Microb 2017; 83:15 [View Article]
    [Google Scholar]
  34. Bauchop T. Inhibition of rumen methanogenesis by methane analogues. J Bacteriol 1967; 94:171–177 [View Article] [PubMed]
    [Google Scholar]
  35. Martinez-Fernandez G, Denman SE, Yang C, Cheung J, Mitsumori M et al. Methane inhibition alters the microbial community, hydrogen flow, and fermentation response in the rumen of cattle. Front Microbiol 2016; 7:1122 [View Article] [PubMed]
    [Google Scholar]
  36. Gunsalus RP, Wolfe RS. ATP activation and properties of the methyl coenzyme M reductase system in Methanobacterium thermoautotrophicum. J Bacteriol 1978; 135:851–857 [View Article] [PubMed]
    [Google Scholar]
  37. Graham DE, White RH. Elucidation of methanogenic coenzyme biosyntheses: from spectroscopy to genomics. Nat Prod Rep 2002; 19:133–147 [View Article] [PubMed]
    [Google Scholar]
  38. Pecher T, Böck A. In vivo susceptibility of halophilic and methanogenic organisms to protein synthesis inhibitors. FEMS Microbiol Lett 1981; 10:295–297 [View Article]
    [Google Scholar]
  39. Weisburg WG, Tanner RS. Aminoglycoside sensitivity of archaebacteria. FEMS Microbiol Lett 1982; 14:307–310 [View Article]
    [Google Scholar]
  40. Argyle JL, Tumbula DL, Leigh JA. Neomycin resistance as a selectable marker in Methanococcus maripaludis. Appl Environ Microbiol 1996; 62:4233–4237 [View Article]
    [Google Scholar]
  41. Whitman WB, Shieh J, Sohn S, Caras DS, Premachandran U. Isolation and characterization of 22 Mesophilic Methanococci. System Appl Microbiol 1986; 7:235–240 [View Article]
    [Google Scholar]
  42. Hendrickson EL, Kaul R, Zhou Y, Bovee D, Chapman P et al. Complete genome sequence of the genetically tractable hydrogenotrophic methanogen Methanococcus maripaludis. J Bacteriol 2004; 186:6956–6969 [View Article] [PubMed]
    [Google Scholar]
  43. Walters AD, Smith SE, Chong JPJ. Shuttle vector system for Methanococcus maripaludis with improved transformation efficiency. Appl Environ Microbiol 2011; 77:2549–2551 [View Article]
    [Google Scholar]
  44. Moore BC, Leigh JA. Markerless mutagenesis in Methanococcus maripaludis demonstrates roles for alanine dehydrogenase, alanine racemase, and alanine permease. J Bacteriol 2005; 187:972–979 [View Article] [PubMed]
    [Google Scholar]
  45. Long F, Wang LL, Lupa B, Whitman BB. A flexible system for cultivation of Methanococcus and other formate-utilizing methanogens. Archaea 2017; 7046026:
    [Google Scholar]
  46. Kearse M, Moir R, Wilson A, Stones-Havas S, Cheung M et al. Geneious Basic: an integrated and extendable desktop software platform for the organization and analysis of sequence data. Bioinformatics 2012; 28:1647–1649 [View Article]
    [Google Scholar]
  47. Oberto J. SyntTax: a web server linking synteny to prokaryotic taxonomy. BMC Bioinform 2013; 14: [View Article]
    [Google Scholar]
  48. Altschul SF, Madden TL, Schaffer AA, Zhang JH, Zhang Z et al. Gapped blast and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 1997; 25:3389–3402 [View Article] [PubMed]
    [Google Scholar]
  49. Long F. Aspects of sulfur metabolism of methane-producing archaeon Methanococcus maripaludis. The University of Georgia PhD Thesis 2017
    [Google Scholar]
  50. Dale AW, Nickelsen L, Scholz F, Hensen C, Oschlies A et al. A revised global estimate of dissolved iron fluxes from marine sediments. Global Biogeochem Cycles 2015; 29:691–707 [View Article]
    [Google Scholar]
  51. de Chanvalon AT, Metzger E, Mouret A, Knoery J, Geslin E et al. Two dimensional mapping of iron release in marine sediments at submillimetre scale. Mar Chem 2017; 191:34–49
    [Google Scholar]
  52. Hildenbrand C, Stock T, Lange C, Rother M, Soppa J. Genome copy numbers and gene conversion in methanogenic archaea. J Bacteriol 2011; 193:734–743 [View Article] [PubMed]
    [Google Scholar]
  53. Lazar V, Nagy I, Spohn R, Csorgo B, Gyorkei A et al. Genome-wide analysis captures the determinants of the antibiotic cross-resistance interaction network. Nat Commun 2014; 5:4352 [View Article] [PubMed]
    [Google Scholar]
  54. Zolova OE, Mady ASA, Garneau-Tsodikova S. Recent developments in bisintercalator natural products. Biopolymers 2010; 93:777–790 [View Article]
    [Google Scholar]
  55. Sarmiento F, Mrázek J. Whitman WB Genome-scale analysis of gene function in the hydrogenotrophic methanogenic archaeon Methanococcus maripaludis. Proc Natl Acad Sci U S A 2013; 110:4726–4731 [View Article] [PubMed]
    [Google Scholar]
  56. Wright GD. Aminoglycoside-modifying enzymes. Curr Opin Microbiol 1999; 2:499–503 [View Article] [PubMed]
    [Google Scholar]
  57. Azucena E, Mobashery S. Aminoglycoside-modifying enzymes: mechanisms of catalytic processes and inhibition. Drug Resist Updat 2001; 4:106–117 [View Article] [PubMed]
    [Google Scholar]
  58. Smigán P, Polák P, Majernik A. Greksák MIsolation and characterization of a neomycin-resistant mutant of Methanobacterium thermoautotrophicum with a lesion in Na+-translocating ATPase (synthase. FEBS Lett 1997; 420:93–96 [View Article] [PubMed]
    [Google Scholar]
  59. Wood JM, Kennedy FS, Wolfe RS. The reaction of multihalogenated hydrocarbons with free and bound reduced vitamin B 12. Biochemistry 1968; 7:1707–1713 [View Article]
    [Google Scholar]
  60. Gottschalk G, Thauer RK. The N+-translocating methyltransferase complex from methanogenic archaea. Biochim Biophys Acta 2001; 5050:28–36
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/acmi/10.1099/acmi.0.000244
Loading
/content/journal/acmi/10.1099/acmi.0.000244
Loading

Data & Media loading...

Supplements

Supplementary material 1

EXCEL

Most cited Most Cited RSS feed