Antibiotics discovery

Bad Bugs, No Drugs. As Antibiotic Discovery Stagnates A Public Health Crisis Brews. A July 2004 white paper by IDSA (www.idsociety.org). 

Antibiotic Discovery year Chemical class Mechanism of action... 

We recommend readers to an informative book on antibiotics. In this chapter, we focus on natural product or natural product derived antibiotics and the discussion of opportunities of antibiotic discovery. 

Dougherty, T. et al. (2002). Microbial genomics and novel antibiotic discovery. New Technol. New Drugs Curr. Pharmaceut. Design 8(13), 1119—1135. 

Flieger, M. et al. (1997). Ergot alkaloids — sources, structures and analytical methods. Folia Microbiol. 42(1), 3-29. Glass, J. et al. (2002). Streptococcus pneumoniae as a genomics platform for broad spectrum antibiotic discovery. Curr. Opin. Microbiol. 5(3), 338—342. 

The personality of scientists, especially when fame or money enters their lives, suggests that scientist are humans first and scientists second. The fact that so many people involved in antibiotic discovery were treated so badly, or treated others so poorly, shows that Nobel Prize winners are not always noble. 

This chapter focuses on a novel antibiotic discovery paradigm. Metallo-hydrolases and Mur ligases are used to illustrate this approach. New methods to identify and prioritize targets, develop screens, and evaluate new inhibitors are discussed. New developments in enzyme-based assays, such as pathway assays, are also presented. This new approach is opening new venues for screening targets that are difficult to screen because substrates are not easily available. 

II. METALLO-HYDROLASES A FAMILY OF TARGETS FOR NOVEL ANTIBIOTIC DISCOVERY... 

Table 1 Candidate Metallo-Hydrolases for New Antibiotic Discovery in Bacteria...

Although a very considerable amount of time and effort was expended in the early days of antibiotic discovery (by this we mean the mid to late 1940s), only three general use antifungal agents entered clinical practice as a result. Perhaps the first clinically used antifungal natural product (our information on... 

In retrospect, neither of these important antimicrobial agents could have been developed if Lilly did not have a fully integrated natural products discovery group that included scientists dedicated to bioconversions of natural products and medicinal chemists dedicated to modifying complex cyclic peptides and other secondary metabolites. This may be a lesson learned to help guide antibiotic discovery and development in the 21st century. 

R. B. Sykes and D. P. Bonner, "Monobactam Antibiotics History and Development," in J. D. Williams and P. Woods, Eds., Aztreonam, The Antibiotic Discovery for Gram-negative Infections, Royal Society Medicine International Congress Symposium Series No. 89, Royal Society Medicine, London, 1985, pp. 3-24. 

Birnbaum J, Kahan FM, Kropp H, MacDonald JS. Carbapenems, a new class of beta-lactam antibiotics. Discovery and development of imipenem/cilastatin. Am J Med 1985 78(6A) 3-21. 

Davis, D.R., McAlpine, J.B., Pazoles, C.J., Talbot, M.K, Alder, E.A., White, C., Jonas, B.M., Murray, B.E., Weinstock, G.M., and Rogers, B.L. (2001) Enterococcus faecalis multi-drug resistance transporters application for antibiotic discovery. Journal of Molecular Microbiology and Biotechnology, 3 (2),... 

In 1952, Conover developed tetracycline (Figure 1.20) from chlortetracycline by removal of its chlorine atom by catalytic hydrogenation, and then oxytetracycline. The discovery prompted an industry-wide search for superior structurally modified antibiotics, which has provided most of the important antibiotic discoveries made since then. 

The years between 1940 and 1959 have been justly called the golden era of antibiotic discovery. During this period every important class of antibacterial antibiotic now known was recognized (Table III). Indeed, many specific drugs (e.g., benzylpenicillin, streptomycin, oxytetracycline, chloramphenicol, neomycin, and erythromycin) which presently occupy major places in therapeutic practice were discovered during that period. 

Table IV. Timing and Source of Significant Antibacterial Antibiotic Discoveries 1939—1969...

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