Chapter 62 : Genomics and Innovation in Antibiotics

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Every newly sequenced genome reveals hitherto-unknown proteins whose roles can then be determined. Secondly, chemotherapeutic agents can be developed to interfere with or enhance those functions. A closely coupled concern is whether the headlong rush into genomics has unreasonably marginalized existing approaches to pharmaceutical innovation. Writing in Nature Biotechnology, David Horrobin observed that, with rare exceptions, most of the top 20 multinational pharmaceutical companies are not generating in-house the new products needed to sustain the rates of growth they have enjoyed in the past. The promise is that genomics, together with combinatorial chemistry and high-throughput screening, can bring relief from the grim scenario. Completed genome sequences, from Haemophilus influenzae in 1995 to Sorangium cellulosum in 2008, not only reveal many hitherto unrecognized targets for attack, but also emphasize how limited are the numbers of bacterial functions that thwart with conventional antibiotics. Comparative genomics assist further in eliminating, as possible candidates, genes which are functional in other organisms but whose activities are no longer required by the pathogen in question. Much surely remains to be gained from the corpus of knowledge (and of bacterial strains) accumulated during decades of conventional research on antibiotics. Many proposals have been made, including searches for new antibiotics using novel test methods, examination of previously unculturable bacteria, innovative culture conditions, and means of overcoming penetration barriers to render drugs effective against organisms they do not at present touch.

Citation: Dixon B. 2009. Genomics and Innovation in Antibiotics, p 292-295. In Animalcules. ASM Press, Washington, DC. doi: 10.1128/9781555817442.ch62
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1. Horrobin, D. F. 2001. Realism in drug discovery—could Cassandra be right? Nat. Biotechnol. 19: 1099 1100.
2. Innes, C. M. J.,, and E. J. Allan. 2001. Induction, growth and antibiotic production of Streptomyces viridifaciens L-form bacteria. J. Appl. Microbiol. 90: 301 308.
3. Waterhouse, R. N.,, H. Buhariwalla,, D. Bourn,, E. J. Rattray,, and L. A. Glover. 1996. CCD detection of lux-marked Pseudomonas syringaepv. phaseolicola L-forms associated with Chinese cabbage and the resulting disease protection against Xanthomonas campestris. Lett. Appl. Microbiol. 22: 262 266.
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