6,963
Views
81
CrossRef citations to date
0
Altmetric
Review

Metagenomics and novel gene discovery

Promise and potential for novel therapeutics

, , &
Pages 399-412 | Received 06 Sep 2013, Accepted 14 Nov 2013, Published online: 01 Apr 2013

References

  • Sleator RD, Shortall C, Hill C. Metagenomics. Lett Appl Microbiol 2008; 47:361 - 6; http://dx.doi.org/10.1111/j.1472-765X.2008.02444.x; PMID: 19146522
  • Rappé MS, Giovannoni SJ. The uncultured microbial majority. Annu Rev Microbiol 2003; 57:369 - 94; http://dx.doi.org/10.1146/annurev.micro.57.030502.090759; PMID: 14527284
  • Knight R, Jansson J, Field D, Fierer N, Desai N, Fuhrman JA, Hugenholtz P, van der Lelie D, Meyer F, Stevens R, et al. Unlocking the potential of metagenomics through replicated experimental design. Nat Biotechnol 2012; 30:513 - 20; http://dx.doi.org/10.1038/nbt.2235; PMID: 22678395
  • Whitman WB, Coleman DC, Wiebe WJ. Prokaryotes: the unseen majority. Proc Natl Acad Sci U S A 1998; 95:6578 - 83; http://dx.doi.org/10.1073/pnas.95.12.6578; PMID: 9618454
  • Amann RI, Ludwig W, Schleifer KH. Phylogenetic identification and in situ detection of individual microbial cells without cultivation. Microbiol Rev 1995; 59:143 - 69; PMID: 7535888
  • Hugenholtz P. Exploring prokaryotic diversity in the genomic era. Genome Biol 2002; 3:S0003; http://dx.doi.org/10.1186/gb-2002-3-2-reviews0003; PMID: 11864374
  • Rinke C, Schwientek P, Sczyrba A, Ivanova NN, Anderson IJ, Cheng JF, Darling A, Malfatti S, Swan BK, Gies EA, et al. Insights into the phylogeny and coding potential of microbial dark matter. Nature 2013; 499:431 - 7; http://dx.doi.org/10.1038/nature12352; PMID: 23851394
  • Furrie E. A molecular revolution in the study of intestinal microflora. Gut 2006; 55:141 - 3; http://dx.doi.org/10.1136/gut.2005.081695; PMID: 16407377
  • Voget S, Leggewie C, Uesbeck A, Raasch C, Jaeger KE, Streit WR. Prospecting for novel biocatalysts in a soil metagenome. Appl Environ Microbiol 2003; 69:6235 - 42; http://dx.doi.org/10.1128/AEM.69.10.6235-6242.2003; PMID: 14532085
  • Santosa DA. Rapid extraction and purification of environmental DNA for molecular cloning applications and molecular diversity studies. Mol Biotechnol 2001; 17:59 - 64; http://dx.doi.org/10.1385/MB:17:1:59; PMID: 11280931
  • Purohit MK, Singh SP. Assessment of various methods for extraction of metagenomic DNA from saline habitats of coastal Gujarat (India) to explore molecular diversity. Lett Appl Microbiol 2009; 49:338 - 44; http://dx.doi.org/10.1111/j.1472-765X.2009.02663.x; PMID: 19712192
  • Delmont TO, Robe P, Clark I, Simonet P, Vogel TM. Metagenomic comparison of direct and indirect soil DNA extraction approaches. J Microbiol Methods 2011; 86:397 - 400; http://dx.doi.org/10.1016/j.mimet.2011.06.013; PMID: 21723887
  • Venter JC, Remington K, Heidelberg JF, Halpern AL, Rusch D, Eisen JA, Wu D, Paulsen I, Nelson KE, Nelson W, et al. Environmental genome shotgun sequencing of the Sargasso Sea. Science 2004; 304:66 - 74; http://dx.doi.org/10.1126/science.1093857; PMID: 15001713
  • Salonen A, Nikkilä J, Jalanka-Tuovinen J, Immonen O, Rajilić-Stojanović M, Kekkonen RA, Palva A, de Vos WM. Comparative analysis of fecal DNA extraction methods with phylogenetic microarray: effective recovery of bacterial and archaeal DNA using mechanical cell lysis. J Microbiol Methods 2010; 81:127 - 34; http://dx.doi.org/10.1016/j.mimet.2010.02.007; PMID: 20171997
  • Thomas T, Gilbert J, Meyer F. Metagenomics - a guide from sampling to data analysis. Microb Inform Exp 2012; 2:3; http://dx.doi.org/10.1186/2042-5783-2-3; PMID: 22587947
  • Béjà O, Aravind L, Koonin EV, Suzuki MT, Hadd A, Nguyen LP, Jovanovich SB, Gates CM, Feldman RA, Spudich JL, et al. Bacterial rhodopsin: evidence for a new type of phototrophy in the sea. Science 2000; 289:1902 - 6; http://dx.doi.org/10.1126/science.289.5486.1902; PMID: 10988064
  • Béjà O, Spudich EN, Spudich JL, Leclerc M, DeLong EF. Proteorhodopsin phototrophy in the ocean. Nature 2001; 411:786 - 9; http://dx.doi.org/10.1038/35081051; PMID: 11459054
  • Liu L, Li Y, Li S, Hu N, He Y, Pong R, Lin D, Lu L, Law M. Comparison of next-generation sequencing systems. J Biomed Biotechnol 2012; 2012:251364; http://dx.doi.org/10.1155/2012/251364; PMID: 22829749
  • Loman NJ, Misra RV, Dallman TJ, Constantinidou C, Gharbia SE, Wain J, Pallen MJ. Performance comparison of benchtop high-throughput sequencing platforms. Nat Biotechnol 2012; 30:434 - 9; http://dx.doi.org/10.1038/nbt.2198; PMID: 22522955
  • Metzker ML. Sequencing technologies - the next generation. Nat Rev Genet 2010; 11:31 - 46; http://dx.doi.org/10.1038/nrg2626; PMID: 19997069
  • Pareek CS, Smoczynski R, Tretyn A. Sequencing technologies and genome sequencing. J Appl Genet 2011; 52:413 - 35; http://dx.doi.org/10.1007/s13353-011-0057-x; PMID: 21698376
  • Schloss PD, Handelsman J. Biotechnological prospects from metagenomics. Curr Opin Biotechnol 2003; 14:303 - 10; http://dx.doi.org/10.1016/S0958-1669(03)00067-3; PMID: 12849784
  • Hess M, Sczyrba A, Egan R, Kim TW, Chokhawala H, Schroth G, Luo S, Clark DS, Chen F, Zhang T, et al. Metagenomic discovery of biomass-degrading genes and genomes from cow rumen. Science 2011; 331:463 - 7; http://dx.doi.org/10.1126/science.1200387; PMID: 21273488
  • Kotik M. Novel genes retrieved from environmental DNA by polymerase chain reaction: current genome-walking techniques for future metagenome applications. J Biotechnol 2009; 144:75 - 82; http://dx.doi.org/10.1016/j.jbiotec.2009.08.013; PMID: 19712711
  • Tuffin M, Anderson D, Heath C, Cowan DA. Metagenomic gene discovery: how far have we moved into novel sequence space?. Biotechnol J 2009; 4:1671 - 83; http://dx.doi.org/10.1002/biot.200900235; PMID: 19946882
  • Singh B, Gautam SK, Verma V, Kumar M, Singh B. Metagenomics in animal gastrointestinal ecosystem: Potential biotechnological prospects. Anaerobe 2008; 14:138 - 44; http://dx.doi.org/10.1016/j.anaerobe.2008.03.002; PMID: 18457965
  • Bell PJ, Sunna A, Gibbs MD, Curach NC, Nevalainen H, Bergquist PL. Prospecting for novel lipase genes using PCR. Microbiology 2002; 148:2283 - 91; PMID: 12177322
  • Knietsch A, Waschkowitz T, Bowien S, Henne A, Daniel R. Construction and screening of metagenomic libraries derived from enrichment cultures: generation of a gene bank for genes conferring alcohol oxidoreductase activity on Escherichia coli. Appl Environ Microbiol 2003; 69:1408 - 16; http://dx.doi.org/10.1128/AEM.69.3.1408-1416.2003; PMID: 12620823
  • Courtois S, Cappellano CM, Ball M, Francou FX, Normand P, Helynck G, Martinez A, Kolvek SJ, Hopke J, Osburne MS, et al. Recombinant environmental libraries provide access to microbial diversity for drug discovery from natural products. Appl Environ Microbiol 2003; 69:49 - 55; http://dx.doi.org/10.1128/AEM.69.1.49-55.2003; PMID: 12513976
  • Feng Z, Kallifidas D, Brady SF. Functional analysis of environmental DNA-derived type II polyketide synthases reveals structurally diverse secondary metabolites. Proc Natl Acad Sci U S A 2011; 108:12629 - 34; http://dx.doi.org/10.1073/pnas.1103921108; PMID: 21768346
  • Owen JG, Reddy BV, Ternei MA, Charlop-Powers Z, Calle PY, Kim JH, Brady SF. Mapping gene clusters within arrayed metagenomic libraries to expand the structural diversity of biomedically relevant natural products. Proc Natl Acad Sci U S A 2013; 110:11797 - 802; http://dx.doi.org/10.1073/pnas.1222159110; PMID: 23824289
  • Banik JJ, Brady SF. Cloning and characterization of new glycopeptide gene clusters found in an environmental DNA megalibrary. Proc Natl Acad Sci U S A 2008; 105:17273 - 7; http://dx.doi.org/10.1073/pnas.0807564105; PMID: 18987322
  • Banik JJ, Craig JW, Calle PY, Brady SF. Tailoring enzyme-rich environmental DNA clones: a source of enzymes for generating libraries of unnatural natural products. J Am Chem Soc 2010; 132:15661 - 70; http://dx.doi.org/10.1021/ja105825a; PMID: 20945895
  • Iwai S, Chai B, Sul WJ, Cole JR, Hashsham SA, Tiedje JM. Gene-targeted-metagenomics reveals extensive diversity of aromatic dioxygenase genes in the environment. ISME J 2010; 4:279 - 85; http://dx.doi.org/10.1038/ismej.2009.104; PMID: 19776767
  • Bayer TS, Widmaier DM, Temme K, Mirsky EA, Santi DV, Voigt CA. Synthesis of methyl halides from biomass using engineered microbes. J Am Chem Soc 2009; 131:6508 - 15; http://dx.doi.org/10.1021/ja809461u; PMID: 19378995
  • Allgaier M, Reddy A, Park JI, Ivanova N, D’haeseleer P, Lowry S, Sapra R, Hazen TC, Simmons BA, VanderGheynst JS, et al. Targeted discovery of glycoside hydrolases from a switchgrass-adapted compost community. PLoS One 2010; 5:e8812; http://dx.doi.org/10.1371/journal.pone.0008812; PMID: 20098679
  • Frost LS, Leplae R, Summers AO, Toussaint A. Mobile genetic elements: the agents of open source evolution. Nat Rev Microbiol 2005; 3:722 - 32; http://dx.doi.org/10.1038/nrmicro1235; PMID: 16138100
  • Jones BV, Marchesi JR. Transposon-aided capture (TRACA) of plasmids resident in the human gut mobile metagenome. Nat Methods 2007; 4:55 - 61; http://dx.doi.org/10.1038/nmeth964; PMID: 17128268
  • Jones BV, Sun F, Marchesi JR. Comparative metagenomic analysis of plasmid encoded functions in the human gut microbiome. BMC Genomics 2010; 11:46; http://dx.doi.org/10.1186/1471-2164-11-46; PMID: 20085629
  • Warburton PJ, Allan E, Hunter S, Ward J, Booth V, Wade WG, Mullany P. Isolation of bacterial extrachromosomal DNA from human dental plaque associated with periodontal disease, using transposon-aided capture (TRACA). FEMS Microbiol Ecol 2011; 78:349 - 54; http://dx.doi.org/10.1111/j.1574-6941.2011.01166.x; PMID: 21711368
  • Zhang T, Zhang XX, Ye L. Plasmid metagenome reveals high levels of antibiotic resistance genes and mobile genetic elements in activated sludge. PLoS One 2011; 6:e26041; http://dx.doi.org/10.1371/journal.pone.0026041; PMID: 22016806
  • Recchia GD, Hall RM. Gene cassettes: a new class of mobile element. Microbiology 1995; 141:3015 - 27; http://dx.doi.org/10.1099/13500872-141-12-3015; PMID: 8574395
  • Stokes HW, Holmes AJ, Nield BS, Holley MP, Nevalainen KM, Mabbutt BC, Gillings MR. Gene cassette PCR: sequence-independent recovery of entire genes from environmental DNA. Appl Environ Microbiol 2001; 67:5240 - 6; http://dx.doi.org/10.1128/AEM.67.11.5240-5246.2001; PMID: 11679351
  • Wu YW, Rho M, Doak TG, Ye Y. Oral spirochetes implicated in dental diseases are widespread in normal human subjects and carry extremely diverse integron gene cassettes. Appl Environ Microbiol 2012; 78:5288 - 96; http://dx.doi.org/10.1128/AEM.00564-12; PMID: 22635997
  • Sureshan V, Deshpande CN, Boucher Y, Koenig JE, Stokes HW, Harrop SJ, Curmi PM, Mabbutt BC, Midwest Center for Structural Genomics. Integron gene cassettes: a repository of novel protein folds with distinct interaction sites. PLoS One 2013; 8:e52934; http://dx.doi.org/10.1371/journal.pone.0052934; PMID: 23349695
  • Akopyants NS, Fradkov A, Diatchenko L, Hill JE, Siebert PD, Lukyanov SA, Sverdlov ED, Berg DE. PCR-based subtractive hybridization and differences in gene content among strains of Helicobacter pylori. Proc Natl Acad Sci U S A 1998; 95:13108 - 13; http://dx.doi.org/10.1073/pnas.95.22.13108; PMID: 9789049
  • Diatchenko L, Lau YF, Campbell AP, Chenchik A, Moqadam F, Huang B, Lukyanov S, Lukyanov K, Gurskaya N, Sverdlov ED, et al. Suppression subtractive hybridization: a method for generating differentially regulated or tissue-specific cDNA probes and libraries. Proc Natl Acad Sci U S A 1996; 93:6025 - 30; http://dx.doi.org/10.1073/pnas.93.12.6025; PMID: 8650213
  • Galbraith EA, Antonopoulos DA, White BA. Suppressive subtractive hybridization as a tool for identifying genetic diversity in an environmental metagenome: the rumen as a model. Environ Microbiol 2004; 6:928 - 37; http://dx.doi.org/10.1111/j.1462-2920.2004.00575.x; PMID: 15305918
  • Meyer QC, Burton SG, Cowan DA. Subtractive hybridization magnetic bead capture: a new technique for the recovery of full-length ORFs from the metagenome. Biotechnol J 2007; 2:36 - 40; http://dx.doi.org/10.1002/biot.200600156; PMID: 17124705
  • Simon C, Daniel R. Construction of small-insert and large-insert metagenomic libraries. In: Streit, WR and Daniel, R, ed(s). Metagenomics - Methods and Protocols New York: Humana Press, 2010.
  • Riesenfeld CS, Schloss PD, Handelsman J. Metagenomics: genomic analysis of microbial communities. Annu Rev Genet 2004; 38:525 - 52; http://dx.doi.org/10.1146/annurev.genet.38.072902.091216; PMID: 15568985
  • Ekkers DM, Cretoiu MS, Kielak AM, Elsas JD. The great screen anomaly--a new frontier in product discovery through functional metagenomics. Appl Microbiol Biotechnol 2012; 93:1005 - 20; http://dx.doi.org/10.1007/s00253-011-3804-3; PMID: 22189864
  • Sleator RD. A beginner’s guide to phylogenetics. Microb Ecol 2013; 66:1 - 4; http://dx.doi.org/10.1007/s00248-013-0236-x; PMID: 23624570
  • Sleator RD. Phylogenetics. Arch Microbiol 2011; 193:235 - 9; http://dx.doi.org/10.1007/s00203-011-0677-x; PMID: 21249334
  • Gabor E, Liebeton K, Niehaus F, Eck J, Lorenz P. Updating the metagenomics toolbox. Biotechnol J 2007; 2:201 - 6; http://dx.doi.org/10.1002/biot.200600250; PMID: 17294408
  • Boni IV. [Diverse molecular mechanisms for translation initiation in prokaryotes]. Mol Biol (Mosk) 2006; 40:658 - 68; http://dx.doi.org/10.1134/S002689330604011X; PMID: 16913225
  • Gabor EM, Alkema WB, Janssen DB. Quantifying the accessibility of the metagenome by random expression cloning techniques. Environ Microbiol 2004; 6:879 - 86; http://dx.doi.org/10.1111/j.1462-2920.2004.00640.x; PMID: 15305913
  • Uchiyama T, Miyazaki K. Functional metagenomics for enzyme discovery: challenges to efficient screening. Curr Opin Biotechnol 2009; 20:616 - 22; http://dx.doi.org/10.1016/j.copbio.2009.09.010; PMID: 19850467
  • Lämmle K, Zipper H, Breuer M, Hauer B, Buta C, Brunner H, Rupp S. Identification of novel enzymes with different hydrolytic activities by metagenome expression cloning. J Biotechnol 2007; 127:575 - 92; http://dx.doi.org/10.1016/j.jbiotec.2006.07.036; PMID: 16963141
  • Chung EJ, Lim HK, Kim JC, Choi GJ, Park EJ, Lee MH, Chung YR, Lee SW. Forest soil metagenome gene cluster involved in antifungal activity expression in Escherichia coli. Appl Environ Microbiol 2008; 74:723 - 30; http://dx.doi.org/10.1128/AEM.01911-07; PMID: 18065615
  • McMahon MD, Guan C, Handelsman J, Thomas MG. Metagenomic analysis of Streptomyces lividans reveals host-dependent functional expression. Appl Environ Microbiol 2012; 78:3622 - 9; http://dx.doi.org/10.1128/AEM.00044-12; PMID: 22427497
  • Craig JW, Chang FY, Kim JH, Obiajulu SC, Brady SF. Expanding small-molecule functional metagenomics through parallel screening of broad-host-range cosmid environmental DNA libraries in diverse proteobacteria. Appl Environ Microbiol 2010; 76:1633 - 41; http://dx.doi.org/10.1128/AEM.02169-09; PMID: 20081001
  • Li Y, Wexler M, Richardson DJ, Bond PL, Johnston AW. Screening a wide host-range, waste-water metagenomic library in tryptophan auxotrophs of Rhizobium leguminosarum and of Escherichia coli reveals different classes of cloned trp genes. Environ Microbiol 2005; 7:1927 - 36; http://dx.doi.org/10.1111/j.1462-2920.2005.00853.x; PMID: 16309391
  • Angelov A, Mientus M, Liebl S, Liebl W. A two-host fosmid system for functional screening of (meta)genomic libraries from extreme thermophiles. Syst Appl Microbiol 2009; 32:177 - 85; http://dx.doi.org/10.1016/j.syapm.2008.01.003; PMID: 19285378
  • Dobrijevic D, Di Liberto G, Tanaka K, de Wouters T, Dervyn R, Boudebbouze S, Binesse J, Blottière HM, Jamet A, Maguin E, et al. High-throughput system for the presentation of secreted and surface-exposed proteins from Gram-positive bacteria in functional metagenomics studies. PLoS One 2013; 8:e65956; http://dx.doi.org/10.1371/journal.pone.0065956; PMID: 23799065
  • Aakvik T, Degnes KF, Dahlsrud R, Schmidt F, Dam R, Yu L, Völker U, Ellingsen TE, Valla S. A plasmid RK2-based broad-host-range cloning vector useful for transfer of metagenomic libraries to a variety of bacterial species. FEMS Microbiol Lett 2009; 296:149 - 58; http://dx.doi.org/10.1111/j.1574-6968.2009.01639.x; PMID: 19459950
  • Kakirde KS, Wild J, Godiska R, Mead DA, Wiggins AG, Goodman RM, Szybalski W, Liles MR. Gram negative shuttle BAC vector for heterologous expression of metagenomic libraries. Gene 2011; 475:57 - 62; http://dx.doi.org/10.1016/j.gene.2010.11.004; PMID: 21112378
  • Terrón-González L, Medina C, Limón-Mortés MC, Santero E. Heterologous viral expression systems in fosmid vectors increase the functional analysis potential of metagenomic libraries. Sci Rep 2013; 3:1107; http://dx.doi.org/10.1038/srep01107; PMID: 23346364
  • Johnston C, Douarre PE, Soulimane T, Pletzer D, Weingart H, MacSharry J, Coffey A, Sleator RD, O’Mahony J. Codon optimisation to improve expression of a Mycobacterium avium ssp. paratuberculosis-specific membrane-associated antigen by Lactobacillus salivarius. Pathog Dis 2013; 68:27 - 38; http://dx.doi.org/10.1111/2049-632X.12040; PMID: 23620276
  • Warren RL, Freeman JD, Levesque RC, Smailus DE, Flibotte S, Holt RA. Transcription of foreign DNA in Escherichia coli. Genome Res 2008; 18:1798 - 805; http://dx.doi.org/10.1101/gr.080358.108; PMID: 18701636
  • Kudla G, Murray AW, Tollervey D, Plotkin JB. Coding-sequence determinants of gene expression in Escherichia coli. Science 2009; 324:255 - 8; http://dx.doi.org/10.1126/science.1170160; PMID: 19359587
  • Roller M, Lucic V, Nagy I, Perica T, Vlahovicek K. Environmental shaping of codon usage and functional adaptation across microbial communities. Nucleic Acids Res 2013; 41:8842 - 52; http://dx.doi.org/10.1093/nar/gkt673; PMID: 23921637
  • Gillespie DE, Brady SF, Bettermann AD, Cianciotto NP, Liles MR, Rondon MR, Clardy J, Goodman RM, Handelsman J. Isolation of antibiotics turbomycin a and B from a metagenomic library of soil microbial DNA. Appl Environ Microbiol 2002; 68:4301 - 6; http://dx.doi.org/10.1128/AEM.68.9.4301-4306.2002; PMID: 12200279
  • Kallifidas D, Kang HS, Brady SF. Tetarimycin A, an MRSA-active antibiotic identified through induced expression of environmental DNA gene clusters. J Am Chem Soc 2012; 134:19552 - 5; http://dx.doi.org/10.1021/ja3093828; PMID: 23157252
  • Chang FY, Brady SF. Cloning and characterization of an environmental DNA-derived gene cluster that encodes the biosynthesis of the antitumor substance BE-54017. J Am Chem Soc 2011; 133:9996 - 9; http://dx.doi.org/10.1021/ja2022653; PMID: 21542592
  • Chang FY, Brady SF. Discovery of indolotryptoline antiproliferative agents by homology-guided metagenomic screening. Proc Natl Acad Sci U S A 2013; 110:2478 - 83; http://dx.doi.org/10.1073/pnas.1218073110; PMID: 23302687
  • Feeney A, Sleator RD. The human gut microbiome: the ghost in the machine. Future Microbiol 2012; 7:1235 - 7; http://dx.doi.org/10.2217/fmb.12.105; PMID: 23075440
  • Sleator RD. The human superorganism - of microbes and men. Med Hypotheses 2010; 74:214 - 5; http://dx.doi.org/10.1016/j.mehy.2009.08.047; PMID: 19836146
  • Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, Fernandes GR, Tap J, Bruls T, Batto JM, et al, MetaHIT Consortium. Enterotypes of the human gut microbiome. Nature 2011; 473:174 - 80; http://dx.doi.org/10.1038/nature09944; PMID: 21508958
  • Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 2012; 486:207 - 14; http://dx.doi.org/10.1038/nature11234; PMID: 22699609
  • Kurokawa K, Itoh T, Kuwahara T, Oshima K, Toh H, Toyoda A, Takami H, Morita H, Sharma VK, Srivastava TP, et al. Comparative metagenomics revealed commonly enriched gene sets in human gut microbiomes. DNA Res 2007; 14:169 - 81; http://dx.doi.org/10.1093/dnares/dsm018; PMID: 17916580
  • Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, et al, MetaHIT Consortium. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010; 464:59 - 65; http://dx.doi.org/10.1038/nature08821; PMID: 20203603
  • Claesson MJ, Jeffery IB, Conde S, Power SE, O’Connor EM, Cusack S, Harris HM, Coakley M, Lakshminarayanan B, O’Sullivan O, et al. Gut microbiota composition correlates with diet and health in the elderly. Nature 2012; 488:178 - 84; http://dx.doi.org/10.1038/nature11319; PMID: 22797518
  • Rea MC, Dobson A, O’Sullivan O, Crispie F, Fouhy F, Cotter PD, Shanahan F, Kiely B, Hill C, Ross RP. Effect of broad- and narrow-spectrum antimicrobials on Clostridium difficile and microbial diversity in a model of the distal colon. Proc Natl Acad Sci U S A 2011; 108:Suppl 1 4639 - 44; http://dx.doi.org/10.1073/pnas.1001224107; PMID: 20616009
  • Rea MC, Sit CS, Clayton E, O’Connor PM, Whittal RM, Zheng J, Vederas JC, Ross RP, Hill C. Thuricin CD, a posttranslationally modified bacteriocin with a narrow spectrum of activity against Clostridium difficile. Proc Natl Acad Sci U S A 2010; 107:9352 - 7; http://dx.doi.org/10.1073/pnas.0913554107; PMID: 20435915
  • Murphy K, O’Sullivan O, Rea MC, Cotter PD, Ross RP, Hill C. Genome mining for radical SAM protein determinants reveals multiple sactibiotic-like gene clusters. PLoS One 2011; 6:e20852; http://dx.doi.org/10.1371/journal.pone.0020852; PMID: 21760885
  • Nature E. The antibiotic alarm. Nature 2013; 495:141; http://dx.doi.org/10.1038/495141a; PMID: 23495392
  • Davies SC. Annual Report of the Chief Medical Officer: Volume Two, 2011; Infections and the rise of antimicrobial resistance Department of Health, London 2013.
  • European Medicines Agency. European Centre for Disease Prevention and Control. Joint technical report: the bacterial challenge—time to react. http://ecdc.europa.eu/en/publications/Publications/0909_TER_The_Bacterial_Challenge_Time_to_React.pdf 2009.
  • Alanis AJ. Resistance to antibiotics: are we in the post-antibiotic era?. Arch Med Res 2005; 36:697 - 705; http://dx.doi.org/10.1016/j.arcmed.2005.06.009; PMID: 16216651
  • Payne DJ, Gwynn MN, Holmes DJ, Pompliano DL. Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat Rev Drug Discov 2007; 6:29 - 40; http://dx.doi.org/10.1038/nrd2201; PMID: 17159923
  • Coates AR, Halls G, Hu Y. Novel classes of antibiotics or more of the same?. Br J Pharmacol 2011; 163:184 - 94; http://dx.doi.org/10.1111/j.1476-5381.2011.01250.x; PMID: 21323894
  • Haiser HJ, Gootenberg DB, Chatman K, Sirasani G, Balskus EP, Turnbaugh PJ. Predicting and manipulating cardiac drug inactivation by the human gut bacterium Eggerthella lenta. Science 2013; 341:295 - 8; http://dx.doi.org/10.1126/science.1235872; PMID: 23869020
  • Wallace BD, Wang H, Lane KT, Scott JE, Orans J, Koo JS, Venkatesh M, Jobin C, Yeh LA, Mani S, et al. Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science 2010; 330:831 - 5; http://dx.doi.org/10.1126/science.1191175; PMID: 21051639
  • Haiser HJ, Turnbaugh PJ. Is it time for a metagenomic basis of therapeutics?. Science 2012; 336:1253 - 5; http://dx.doi.org/10.1126/science.1224396; PMID: 22674325
  • Roeselers G, Bouwman J, Venema K, Montijn R. The human gastrointestinal microbiota--an unexplored frontier for pharmaceutical discovery. Pharmacol Res 2012; 66:443 - 7; http://dx.doi.org/10.1016/j.phrs.2012.09.007; PMID: 23000437
  • Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA. Diversity of the human intestinal microbial flora. Science 2005; 308:1635 - 8; http://dx.doi.org/10.1126/science.1110591; PMID: 15831718
  • Sleator RD. Probiotics -- a viable therapeutic alternative for enteric infections especially in the developing world. Discov Med 2010; 10:119 - 24; PMID: 20807472
  • Sleator RD, Hill C. Rational design of improved pharmabiotics. J Biomed Biotechnol 2009; 2009:275287; http://dx.doi.org/10.1155/2009/275287; PMID: 19753318
  • Watson D, Sleator RD, Hill C, Gahan CG. Enhancing bile tolerance improves survival and persistence of Bifidobacterium and Lactococcus in the murine gastrointestinal tract. BMC Microbiol 2008; 8:176; http://dx.doi.org/10.1186/1471-2180-8-176; PMID: 18844989
  • Sleator RD, Hill C. ‘Bioengineered Bugs’ - a patho-biotechnology approach to probiotic research and applications. Med Hypotheses 2008; 70:167 - 9; http://dx.doi.org/10.1016/j.mehy.2007.03.008; PMID: 17452084
  • Sleator RD, Hill C. New frontiers in probiotic research. Lett Appl Microbiol 2008; 46:143 - 7; http://dx.doi.org/10.1111/j.1472-765X.2007.02293.x; PMID: 18028323
  • Sleator RD, Hill C. Designer probiotics: a potential therapeutic for Clostridium difficile?. J Med Microbiol 2008; 57:793 - 4; http://dx.doi.org/10.1099/jmm.0.47697-0; PMID: 18480340
  • Sleator RD, Hill C. Battle of the bugs. Science 2008; 321:1294 - 5; http://dx.doi.org/10.1126/science.321.5894.1294b; PMID: 18772416
  • Sleator RD, Hill C. Patho-biotechnology; using bad bugs to make good bugs better. Sci Prog 2007; 90:1 - 14; http://dx.doi.org/10.3184/003685007780440530; PMID: 17455762
  • Sleator RD, Hill C. Patho-biotechnology: using bad bugs to do good things. Curr Opin Biotechnol 2006; 17:211 - 6; http://dx.doi.org/10.1016/j.copbio.2006.01.006; PMID: 16459072
  • FAO/WHO. Expert consultation on evaluation of health and nutritional properties of probiotics in food including milk powder with live lactic acid bacteria. FAO/WHO (Food and Agriculture Organization/World Health Organization) Cordoba, Argentina: WHO 2001.
  • Paton AW, Morona R, Paton JC. A new biological agent for treatment of Shiga toxigenic Escherichia coli infections and dysentery in humans. Nat Med 2000; 6:265 - 70; http://dx.doi.org/10.1038/73111; PMID: 10700227
  • Focareta A, Paton JC, Morona R, Cook J, Paton AW. A recombinant probiotic for treatment and prevention of cholera. Gastroenterology 2006; 130:1688 - 95; http://dx.doi.org/10.1053/j.gastro.2006.02.005; PMID: 16697733
  • Paton AW, Jennings MP, Morona R, Wang H, Focareta A, Roddam LF, Paton JC. Recombinant probiotics for treatment and prevention of enterotoxigenic Escherichia coli diarrhea. Gastroenterology 2005; 128:1219 - 28; http://dx.doi.org/10.1053/j.gastro.2005.01.050; PMID: 15887106
  • Paton AW, Morona R, Paton JC. Designer probiotics for prevention of enteric infections. Nat Rev Microbiol 2006; 4:193 - 200; http://dx.doi.org/10.1038/nrmicro1349; PMID: 16462752
  • Paton AW, Morona R, Paton JC. Bioengineered microbes in disease therapy. Trends Mol Med 2012; 18:417 - 25; http://dx.doi.org/10.1016/j.molmed.2012.05.006; PMID: 22721939
  • Rosberg-Cody E, Stanton C, O’Mahony L, Wall R, Shanahan F, Quigley EM, Fitzgerald GF, Ross RP. Recombinant lactobacilli expressing linoleic acid isomerase can modulate the fatty acid composition of host adipose tissue in mice. Microbiology 2011; 157:609 - 15; http://dx.doi.org/10.1099/mic.0.043406-0; PMID: 21178166
  • Choi HJ, Ahn JH, Park SH, Do KH, Kim J, Moon Y. Enhanced wound healing by recombinant Escherichia coli Nissle 1917 via human epidermal growth factor receptor in human intestinal epithelial cells: therapeutic implication using recombinant probiotics. Infect Immun 2012; 80:1079 - 87; http://dx.doi.org/10.1128/IAI.05820-11; PMID: 22184415
  • Culligan EP, Hill C, Sleator RD. Probiotics and gastrointestinal disease: successes, problems and future prospects. Gut Pathog 2009; 1:19; http://dx.doi.org/10.1186/1757-4749-1-19; PMID: 19930635
  • Culligan EP, Marchesi JR, Hill C, Sleator RD. Mining the human gut microbiome for novel stress resistance genes. Gut Microbes 2012; 3:394 - 7; http://dx.doi.org/10.4161/gmic.20984; PMID: 22688726
  • Sleator RD, Hill C. Engineered pharmabiotics with improved therapeutic potential. Hum Vaccin 2008; 4:271 - 4; http://dx.doi.org/10.4161/hv.4.4.6315; PMID: 18682694
  • Mattila-Sandholm T, Myllärinen P, Crittenden R, Mogensen G, Fondén R, Saarela M. Technological challenges for future probiotic foods. Int Dairy J 2002; 12:173 - 82; http://dx.doi.org/10.1016/S0958-6946(01)00099-1
  • Sleator RD, Francis GA, O’Beirne D, Gahan CG, Hill C. Betaine and carnitine uptake systems in Listeria monocytogenes affect growth and survival in foods and during infection. J Appl Microbiol 2003; 95:839 - 46; http://dx.doi.org/10.1046/j.1365-2672.2003.02056.x; PMID: 12969299
  • Sleator RD, Gahan CG, Abee T, Hill C. Identification and disruption of BetL, a secondary glycine betaine transport system linked to the salt tolerance of Listeria monocytogenes LO28. Appl Environ Microbiol 1999; 65:2078 - 83; PMID: 10224004
  • Sleator RD, O’Driscoll B, Hill C, Gahan CGM. Analysis of the role of betL in contributing to the growth and survival of Listeria monocytogenes LO28. Int J Food Microbiol 2000; 60:261 - 8; http://dx.doi.org/10.1016/S0168-1605(00)00316-0; PMID: 11016615
  • Hoffmann RF, McLernon S, Feeney A, Hill C, Sleator RD. A single point mutation in the listerial betL σ (A) -dependent promoter leads to improved osmo- and chill-tolerance and a morphological shift at elevated osmolarity. Bioengineered 2013; 4:4; http://dx.doi.org/10.4161/bioe.24094; PMID: 23478432
  • Sheehan VM, Sleator RD, Fitzgerald GF, Hill C. Heterologous expression of BetL, a betaine uptake system, enhances the stress tolerance of Lactobacillus salivarius UCC118. Appl Environ Microbiol 2006; 72:2170 - 7; http://dx.doi.org/10.1128/AEM.72.3.2170-2177.2006; PMID: 16517668
  • Sheehan VM, Sleator RD, Hill C, Fitzgerald GF. Improving gastric transit, gastrointestinal persistence and therapeutic efficacy of the probiotic strain Bifidobacterium breve UCC2003. Microbiology 2007; 153:3563 - 71; http://dx.doi.org/10.1099/mic.0.2007/006510-0; PMID: 17906153
  • FAO/WHO. Working Group on Drafting Guidelines for the Evaluation of Probiotics in Food. 2002. Available from: http://www.who.int/foodsafety/fs_management/en/probiotic_guidelines.pdf
  • Yoon MY, Lee KM, Yoon Y, Go J, Park Y, Cho YJ, Tannock GW, Yoon SS. Functional screening of a metagenomic library reveals operons responsible for enhanced intestinal colonization by gut commensal microbes. Appl Environ Microbiol 2013; 79:3829 - 38; http://dx.doi.org/10.1128/AEM.00581-13; PMID: 23584783
  • Kimoto H, Nomura M, Kobayashi M, Mizumachi K, Okamoto T. Survival of lactococci during passage through mouse digestive tract. Can J Microbiol 2003; 49:707 - 11; http://dx.doi.org/10.1139/w03-092; PMID: 14735220
  • Cotter PD, Hill C. Surviving the acid test: responses of gram-positive bacteria to low pH. [table of contents.] Microbiol Mol Biol Rev 2003; 67:429 - 53; http://dx.doi.org/10.1128/MMBR.67.3.429-453.2003; PMID: 12966143
  • Guazzaroni ME, Morgante V, Mirete S, González-Pastor JE. Novel acid resistance genes from the metagenome of the Tinto River, an extremely acidic environment. Environ Microbiol 2013; 15:1088 - 102; http://dx.doi.org/10.1111/1462-2920.12021; PMID: 23145860
  • Culligan EP, Sleator RD, Marchesi JR, Hill C. Functional metagenomics reveals novel salt tolerance loci from the human gut microbiome. ISME J 2012; 6:1916 - 25; http://dx.doi.org/10.1038/ismej.2012.38; PMID: 22534607
  • Sleator RD, Hill C. Bacterial osmoadaptation: the role of osmolytes in bacterial stress and virulence. FEMS Microbiol Rev 2002; 26:49 - 71; http://dx.doi.org/10.1111/j.1574-6976.2002.tb00598.x; PMID: 12007642
  • Ridlon JM, Kang DJ, Hylemon PB. Bile salt biotransformations by human intestinal bacteria. J Lipid Res 2006; 47:241 - 59; http://dx.doi.org/10.1194/jlr.R500013-JLR200; PMID: 16299351
  • Jones BV, Begley M, Hill C, Gahan CG, Marchesi JR. Functional and comparative metagenomic analysis of bile salt hydrolase activity in the human gut microbiome. Proc Natl Acad Sci U S A 2008; 105:13580 - 5; http://dx.doi.org/10.1073/pnas.0804437105; PMID: 18757757
  • Jones ML, Tomaro-Duchesneau C, Martoni CJ, Prakash S. Cholesterol lowering with bile salt hydrolase-active probiotic bacteria, mechanism of action, clinical evidence, and future direction for heart health applications. Expert Opin Biol Ther 2013; 13:631 - 42; http://dx.doi.org/10.1517/14712598.2013.758706; PMID: 23350815
  • Kumar M, Nagpal R, Kumar R, Hemalatha R, Verma V, Kumar A, Chakraborty C, Singh B, Marotta F, Jain S, Yadav H.. Cholesterol-lowering probiotics as potential biotherapeutics for metabolic diseases. Exp Diabetes Res. 2012; 2012:902917
  • Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci 2012; 13:701 - 12; http://dx.doi.org/10.1038/nrn3346; PMID: 22968153
  • Barrett E, Ross RP, O’Toole PW, Fitzgerald GF, Stanton C. γ-Aminobutyric acid production by culturable bacteria from the human intestine. J Appl Microbiol 2012; 113:411 - 7; http://dx.doi.org/10.1111/j.1365-2672.2012.05344.x; PMID: 22612585
  • Collins SM, Bercik P. The relationship between intestinal microbiota and the central nervous system in normal gastrointestinal function and disease. Gastroenterology 2009; 136:2003 - 14; http://dx.doi.org/10.1053/j.gastro.2009.01.075; PMID: 19457424
  • Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG. The probiotic Bifidobacteria infantis: An assessment of potential antidepressant properties in the rat. J Psychiatr Res 2008; 43:164 - 74; http://dx.doi.org/10.1016/j.jpsychires.2008.03.009; PMID: 18456279
  • Lyte M. Probiotics function mechanistically as delivery vehicles for neuroactive compounds: Microbial endocrinology in the design and use of probiotics. Bioessays 2011; 33:574 - 81; http://dx.doi.org/10.1002/bies.201100024; PMID: 21732396
  • Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, Bienenstock J, Cryan JF. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A 2011; 108:16050 - 5; http://dx.doi.org/10.1073/pnas.1102999108; PMID: 21876150
  • Dinan TG, Stanton C, Cryan JF. Psychobiotics: a novel class of psychotropic. Biol Psychiatry 2013; 74:720 - 6; http://dx.doi.org/10.1016/j.biopsych.2013.05.001; PMID: 23759244
  • Steidler L, Neirynck S, Huyghebaert N, Snoeck V, Vermeire A, Goddeeris B, Cox E, Remon JP, Remaut E. Biological containment of genetically modified Lactococcus lactis for intestinal delivery of human interleukin 10. Nat Biotechnol 2003; 21:785 - 9; http://dx.doi.org/10.1038/nbt840; PMID: 12808464
  • Ahmad SI, Kirk SH, Eisenstark A. Thymine metabolism and thymineless death in prokaryotes and eukaryotes. Annu Rev Microbiol 1998; 52:591 - 625; http://dx.doi.org/10.1146/annurev.micro.52.1.591; PMID: 9891809
  • Braat H, Rottiers P, Hommes DW, Huyghebaert N, Remaut E, Remon JP, van Deventer SJ, Neirynck S, Peppelenbosch MP, Steidler L. A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn’s disease. Clin Gastroenterol Hepatol 2006; 4:754 - 9; http://dx.doi.org/10.1016/j.cgh.2006.03.028; PMID: 16716759
  • Kong W, Brovold M, Koeneman BA, Clark-Curtiss J, Curtiss R 3rd. Turning self-destructing Salmonella into a universal DNA vaccine delivery platform. Proc Natl Acad Sci U S A 2012; 109:19414 - 9; http://dx.doi.org/10.1073/pnas.1217554109; PMID: 23129620
  • Bahey-El-Din M. Lactococcus lactis-based vaccines from laboratory bench to human use: an overview. Vaccine 2012; 30:685 - 90; http://dx.doi.org/10.1016/j.vaccine.2011.11.098; PMID: 22154771
  • O’ Driscoll A, Sleator RD. Synthetic DNA: the next generation of big data storage. Bioengineered 2013; 4:123 - 5; http://dx.doi.org/10.4161/bioe.24296; PMID: 23514938
  • Sleator RD. Digital biology: a new era has begun. Bioengineered 2012; 3:311 - 2; http://dx.doi.org/10.4161/bioe.22367; PMID: 23099453
  • Chakrabarty AM. Bioengineered bugs, drugs and contentious issues in patenting. Bioeng Bugs 2010; 1:2 - 8; http://dx.doi.org/10.4161/bbug.1.1.9850; PMID: 21327122