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Self-resistance mechanisms to DNA-damaging antitumor antibiotics in actinobacteria
- Tenconi, Elodie, Rigali, Sébastien
- Current opinion in microbiology 2018 v.45 pp. 100-108
- DNA, Streptomyces coelicolor, anthracyclines, antibiotics, cytotoxicity, drug therapy, morphogenesis, neoplasm cells, programmed cell death, suicide
- Streptomyces and few other Actinobacteria naturally produce compounds currently used in chemotherapy for being cytotoxic against various types of tumor cells by damaging the DNA structure and/or inhibiting DNA functions. DNA-damaging antitumor antibiotics belong to different classes of natural compounds that are structurally unrelated such as anthracyclines, bleomycins, enediynes, mitomycins, and prodiginines. By targeting a ubiquitous molecule and housekeeping functions, these compounds are also cytotoxic to their producer. How DNA-damaging antitumor antibiotics producing actinobacteria avoid suicide is the theme of the current review which illustrates the different strategies developed for self-resistance such as toxin sequestration, efflux, modification, destruction, target repair/protection, or stochastic activity. Finally, the observed spatio-temporal correlation between cell death, morphogenesis, and prodiginine production in S. coelicolor suggests a new physiological role for these molecules, that, together with their self-resistance mechanisms, would function as new types of toxin-antitoxin systems recruited in programmed cell death processes of the producer.