Abstract
Over the years, antibiotics have provided an effective treatment for a number of microbial diseases. However recently, there has been an increase in resistant microorganisms that have adapted to our current antibiotics. One of the most dangerous pathogens is methicillin-resistant Staphylococcus aureus (MRSA). With the rise in the cases of MRSA and other resistant pathogens such as vancomycin-resistant Staphylococcus aureus, the need for new antibiotics increases every day. Many challenges face the discovery and development of new antibiotics, making it difficult for these new drugs to reach the market, especially since many of the pharmaceutical companies have stopped searching for antibiotics. With the advent of genome sequencing, new antibiotics are being found by the techniques of genome mining, offering hope for the future.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Infectious Disease Society of America (2004) Bad bugs, no drugs: as antibiotic discovery stagnates… a public health crisis brews. pp. 1–35 http://www.fda.gov/ohrms/dockets/dockets/04s0233/04s-0233-c000005-03-IDSA-vol1.pdf
ScienceDaily (2010) Mining bacterial genome reveals valuable “hidden” drugs. Aug. 2. http://www.sciencedaily.com/releases/2010/08/100801201329.htm
CDC (2012) CDC reminds clinical laboratories and healthcare infection preventionists of their role in the search and containment of vancomycin-resistant Staphylococcus aureus (VRSA). http://www.cdc.gov/HAI/settings/lab/vrsa_lab_search_containment.html
Baltz RH (2008) Renaissance in antibacterial discovery from actinomycetes. Curr Opin Pharmacol 8:557–563
Bergmann S, Shümann J, Scherlach K, Lange C, Brakhage AA, Hertweck C (2007) Genomics-driven discovery of PKS-NPRS hybrid metabolites from Aspergillus nidulans. Nat Chem Biol 3:213–217
Bok JW, Hoffmeister D, Maggio-Hall LA, Murillo R, Glasner JD, Keller NP (2006) Genomic mining for Aspergillus natural products. Chem Biol 13:1–7
Brakhage AA, Schroeckh V (2011) Fungal secondary metabolites—strategies to activate silent gene clusters. Fungal Genet Biol 48:15–22
Challis GL, Ravel J (2000) Coelichelin, a new peptide siderophore encoded by the Streptomyces coelicolor genome: structure prediction from the sequence of its non-ribosomal peptide synthetase. FEMS Microbiol Lett 187:111–114
Challis GL (2008) Mining microbial genomes for new natural products and biosynthetic pathways. Microbiology 154:1555–1569
Chiang Y, Szewczyk E, Nayak T, Davidson AD, Sanchez JF, Lo H, Ho W, Simityan H, Kuo E, Praseuth A, Watanabe K, Oakley BR, Wang CCC (2008) Molecular genetic mining of the Aspergillus secondary metabolome: discovery of the emericellamide biosynthetic pathway. Chem Biol 15:527–532
Christoffersen RE (2006) Antibiotics—an investment worth making? Nat Biotechnol 24:1512–1514
Clatworthy AE, Pierson E, Hung DT (2007) Targeting virulence: a new paradigm for antimicrobial therapy. Nat Chem Biol 3:541–548
Cosgrove SE, Sakoulas G, Perencevich EN, Schwaber MJ, Karchmer AW, Carmeli Y (2006) Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteremia: a meta-analysis. Clin Infect Dis 36:53–59
Demain AL, Spizek J (2012) The antibiotic crisis. In: Tegos G, Mylonakis E (eds) Antimicrobial drug discovery: emerging strategies. CAB International, Wallingford, UK, pp 26–43
Fox JL (2006) The business of developing antibacterials. Nat Biotechnol 24:1521–1528
Gross H, Stockwell VO, Henkels MD, Nowak-Thompson B, Loper JE, Gerwick WH (2007) The genomisotopic approach: a systematic method to isolate products of orphan biosynthetic gene clusters. Chem Biol 14:53–63
Gross H (2007) Strategies to unravel the function of orphan biosynthesis pathways: recent examples and future prospects. Appl Microbiol Biotechnol 75:267–277
Gross H (2009) Genomic mining—a concept for the discovery of new bioactive natural products. Curr Opin Drug Discov Devel 12:207–219
Gwynn MN, Portnoy A, Rittenhouse SF, Payne DJ (2010) Challenges of antibacterial discovery revisited. Ann NY Acad Sci 1213:5–19
Henry C (2005) Genome mining hits pay dirt: DNA sequencing guides discovery and isolation of microbial natural product. Chem Eng News. http://pubs.acs.org/cen/news/83/i38/8338notw8.html
Laureti L, Song L, Huang S, Corre C, Leblond P, Challis GL, Aigle B (2011) Identification of a bioactive 51-membered macrolide complex by activation of a silent polyketide synthase in Streptomyces ambofaciens. Proc Natl Acad Sci USA 108:6258–6263
Lautru S, Deeth RJ, Bailey LM, Challis GL (2005) Discovery of a new peptide natural product by Streptomyces coelicolor genome mining. Nat Chem Biol 1:265–269
Lin X, Hopson R, Cane DE (2006) Genome mining in Streptomyces coelicolor: molecular cloning and characterization of a new sequiterpene synthase. J Amer Chem Soc 128:6022–6023
Livermore DM (2000) Antibiotic resistance in staphylococci. Int J Antimicrob Agents 16:S3–S10
Morris GJ Jr (2008) Germ warfare: are we creating a new generation of superbugs? Nutrition Action Health Letter: Center for Science in the Public Interest. pp. 3–6
Nikolouli K, Mossialos D (2012) Bioactive compounds synthesized by non-ribosomal peptide synthetases and type-I polyketide synthases discovered through genome-mining and metagenomics. Biotechnol Lett 34:1393–1403
Payne DJ, Gwynn MN, Holmes DJ, Pompliano DL (2007) Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat Rev Drug Disc 6:29–40
Pollack A (2010) Rising threat of infections unfazed by antibiotics. New York Times. http://www.nytimes.com/2010/02/27/business/27germ.html?_r=0
Ratti E, Trist D (2001) Continuing evolution of the drug discovery process in the pharmaceutical industry. Pure Appl Chem 73:67–75
Scherlach K, Hertweck C (2006) Discovery of aspoquinolones A–D, prenylated quinoline-2-one alkaloids from Aspergillus nidulans, motivated by genome mining. Org Biomol Chem 4:3517–3520
Sellers LJ (2003) Big pharma bails on anti-infectives research. Pharma Exec 23(12):22
Song L, Barona-Gomez F, Corre C, Xiang L, Udwary DW, Austin MB, Noel JP, Moore BS, Challis GL (2006) Type III polyketide sythase β-ketoacyl-ACP starter unit and ethylmalonyl-CoA extender unit selectivity discovered by Streptomyces coelicolor genome mining. J Amer Chem Soc 128:14754–14755
Spellberg B, Powers JH, Brass EP, Miller LG, Edwards JE Jr (2004) Trends in antimicrobial drug development: implications for the future. Clin Infect Dis 38:1279–1286
Spizek J, Novotna J, Rezanka T, Demain AL (2010) Do we need new antibiotics? The search for new targets and new compounds. J Ind Microbiol Biotechnol 37:1241–1248
Wenzel RP (2004) The antibiotic pipeline—challenges, costs, and values. N Engl J Med 351:523–526
Zhang L, Kezhi Y, Zhang Y, Huang R, Bian J, Zheng C, Sun H, Chen Z, Sun N, An R, Zhao W, Zhuo Y, You J, Song Y, Yu Z, Liu Z, Yang K, Gao H, Dai H, Zhang X, Wang J, Fu C, Pei G, Liu J, Zhang S, Goodfellow M, Jiang Y, Kuai J, Zhou G, Chen X (2007) High-throughput synergy screening identifies microbial metabolites as combination agents for the treatment of fungal infections. Proc Natl Acad Sci USA 104:4606–4611
Acknowledgments
We acknowledge the assistance of the R.I.S.E. honors course, the participation of Drew faculty Kathleen Madden and Jane Liu, and the encouragement given by R.I.S.E Director Dr. Jon Kettenring and R.I.S.E Administrator Miriam Donahue. The first three authors of the paper are undergraduate students of Drew University.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Scheffler, R.J., Colmer, S., Tynan, H. et al. Antimicrobials, drug discovery, and genome mining. Appl Microbiol Biotechnol 97, 969–978 (2013). https://doi.org/10.1007/s00253-012-4609-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00253-012-4609-8