Self-resistance mechanisms to DNA-damaging antitumor antibiotics in actinobacteria.

Self-resistance mechanisms to DNA-damaging antitumor antibiotics in actinobacteria. Curr Opin Microbiol. 2018 Apr 08;45:100-108 Authors: Tenconi E, Rigali S Abstract 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. PMID: 29642052 [PubMed - as supplied by publisher]
Source: Current Opinion in Microbiology - Category: Microbiology Authors: Tags: Curr Opin Microbiol Source Type: research