Abstract
Relatively few new antibiotics targeted against nucleic acids have been developed in the last 50 years. Rifamycins and a wide group of related microbial compounds block RNA synthesis by specific inhibition of bacterial RNA polymerase without interacting with mammalian analog enzymes. Others, such as actinomycins or doxorubicin, interfere with transcription in both bacterial and mammalian systems and may be used as antitumor drugs because the fast growth favors a higher percentage of death in malignant cells respect to normal counterparts. Another group of antibiotics interferes with DNA synthesis by acting on the bacterial DNA gyrase involved in the mechanism of replication of closed-circular DNA. Most members of this group, including aminocoumarin antibiotics, work by binding to the ATPase active site located on one subunit of the gyrase enzyme. Moreover, antibiotics effective against mammalian topoisomerases or able to prevent normal DNA distribution into daughter cells are being also used as antineoplastic drugs. In spite of the wide variety of mechanisms classically invoked to explain the primary action of antibacterial drugs, a new view is emerging whereby the killing damage behind all major classes of antibiotics appears to stem from the generation of destructive molecules that fatally damage nucleic acids through a long chain of cellular events.
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Gacto, M., Madrid, M., Franco, A., Soto, T., Cansado, J., Vicente-Soler, J. (2014). The Cornerstone of Nucleic Acid-Affecting Antibiotics in Bacteria. In: Villa, T., Veiga-Crespo, P. (eds) Antimicrobial Compounds. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-40444-3_6
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