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A chemical defence against phage infection.

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PubMed ID: 30518855

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Kronheim S, Daniel-Ivad M, Duan Z, Hwang S, Wong AI, Mantel I, Nodwell JR, Maxwell KL

Nature. 12 2018. doi: 10.1038/s41586-018-0767-x

COMMENT: In this work the authors report a new chemical anti-phage defence system frequent in Streptomyces that by means of the insertion of three naturally produced molecules into DNA  blocks phage replication.

OBJECTIVE:

To discover and study a new anti-phage defence system with a probably important evolutionary role for bacteria.

RESULTS: 

Streptomyces species commonly produce secondary metabolites that provide them with a chemical anti-phage defence system. In contrast to other bacterial anti-phage systems (which are usually specific to a narrow range of phages), small molecules such as DNA-intercalating compounds could provide broad protection against all dsDNA phages, by targeting an essential and universal step early in the life cycle of a phage.

... we observed that daunorubicin was able to block the replication of a variety of E. coli dsDNA phages. We found that all types of dsDNA phages, including those belongingto the siphophage, myophage and podophage families were inhibited by daunorubicin, whereas the single-stranded DNA (ssDNA) phage M13 was not. We tested two Pseudomonas aeruginosa phages and found that these phages were inhibited as well

CONCLUSIONS: 

We show that three naturally produced molecules that insert into DNA are able to block phage replication, whereas molecules that target DNA by other mechanisms do not. Because double-stranded DNA phages are the most numerous group in the biosphere and the production of secondary metabolites by bacteria is ubiquitous, this mechanism of anti-phage defence probably has a major evolutionary role in shaping bacterial communities.

... because the Streptomyces genus is predicted to be capable of producing on the order of 100,000 antimicrobial compounds, most of which are as-yet uncharacterized, we expect that other classes of anti-phage molecules also exist. Identification of these compounds will reveal new groups of bioactive compounds that, similar to the anthracyclines used in cancer treatment, may have broad applicability for therapeutic purposes.

 

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Raquel Tobes