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Bacteria engages in chemical warfare against viruses

Getty / AurichBacteria have many ways to fight the viruses that plague them, called phages. The CRISPR-Cas system and restriction…

 Bacteria engage in chemical warfare against viruses

Getty / Aurich

Bacteria have many ways to fight the viruses that plague them, called phages. The CRISPR-Cas system and restriction enzymes that cleave phage DNA are best understood, but there are others. They use a variety of mechanisms and stop phage at different stages of infection, but they all depend on biological players: proteins and RNA. New work has only shown that bacteria can use chemical weapons as well.

Bacteria produce a wide range of active small molecules that are not essential for survival but provide a growth benefit. Some of these small molecules, which kill their other microbes, are already used (by us) as antibiotics. It was also observed more than fifty years ago that bacteria make molecules that can inhibit the growth of phages. But it was not clear if these molecules were made specifically because they lowered the phages. Only now with the background knowledge that (a) bacteria produce many bioactive compounds, many of which fight other microorganisms, and that (b) phages are a large bacterial skin, researchers thought to control.

screened 4,960 compounds for their ability to protect E. coli from phage infection and found 1

1 as a customer. Nine out of the 11 were those called DNA intercalators. The nucleotides that comprise DNA (A, T, C and G) are flat molecules, and stacked parallel to each other along the DNA helix. DNA intercalation agent slides in between, interference with copy of DNA during cell division.

Streptomyces are soil bacteria that are a real supply of drugs. They make more than two thirds of the antibiotics we use, and they make four of the DNA-intercalating compounds identified in this screen, which are already used as cancer drugs. To determine whether these molecules work in nature to deter phage infection as they do in the lab, researchers gathered Streptomyces from all over the world, Bangladesh, Canada, China, India, Jamaica and exposed them to an experimental battery.

They found that the DNA intercalating substances (the chemicals daunorubicin and doxorubicin were the representatives used) made by these bugs were effective in protecting them from pharyngeal infection and that the ability to make them is quite well preserved; About 30 percent of the Streptomyces strains that they investigated could do it.

The agents block one step early in the infection: after the phage has injected its DNA into the bacterial host cell, but before the DNA is copied. The authors speculate that phage DNA is particularly vulnerable at this time on the low levels of intercalating agents produced by the bacteria, perhaps because it has not yet accumulated a protective shield of DNA binding proteins. These chemicals effectively block the replication of all double-stranded DNA phages. Because they can diffuse from the cell that makes them, the cells that produce them can defend an entire bacterial community.

Biologists have long called intercalation agents to visualize DNA: ethidium bromide is visible under ultraviolet light and used to stain DNA in the lab; Propidium iodide is a red fluorescent dye commonly used to see the cell’s relative DNA content during the cell cycle analysis (it helps us differentiate between the cells that have copied their DNA but not yet divided from those who do not). But bacteria have apparently used them too far beyond ours.

Nature 2018. DOI: 10.1038 / s41586-018-0767x (To DOIs).

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