细菌如何识别自身DNA

It may come as a bit of a surprise to learn that bacteria have an immune system -- in their case to fight off invasive viruses called phages. And like any immune system -- from single-celled to human -- the first challenge of the bacterial¹ immune system is to detect the difference between "foreign" and "self." This is far from simple, as viruses, bacteria and all other living things are made of DNA² and proteins. A group of researchers at the Weizmann Institute of Science and Tel Aviv University has now revealed exactly how bacteria do this. Their results were published online today in Nature. "In most environments, phages are around ten times more abundant than bacteria. And, like all viruses, phages use the host cell's replication machinery³ to make copies of themselves," says Prof. Rotem Sorek of the Weizmann Institute's Molecular⁴ Genetics Department. "And they are constantly evolving new ways to do this. So bacteria need a very active immune system to survive."   But until recently, scientists were not even sure that bacteria had a so-called adaptive immune system -- one that "remembers" a past encounter to produce a targeted response. That changed several years ago when a bacterial adaptive system called CRISPR was discovered. The CRISPR immune mechanism⁶ is not just crucial to the bacteria, it has a major impact on our daily lives: It is used today, for example, to protect the "good" bacteria that make yogurt and cheese. And it may also affect our future: Scientists have figured out how to use the ingenious CRISPR system to "edit" the human genome -- making it a handy tool for a wide range of clinical applications.   To remember an infection, the CRISPR system grabs a short sequence from the invading viral DNA and inserts it straight into the bacterial genome. The bits of phage DNA are stored in special sections of the genome; these form the immune memory. In subsequent infections, CRISPR uses these sequences to create short strands⁸ of RNA that fit the genetic⁵ sequence of the phages' kin⁷. Protein complexes attached to the RNA then identify the phage DNA and destroy it.   Selectivity is clearly an issue for such a system: Previous research in Sorek's lab had shown that mistakenly grabbing bits of self-DNA can cause the bacterial cell to suffer a sort of autoimmune disease in which it attacks its own DNA, and the results may be fatal to the bacteria. With around 100 times more self- than foreign DNA inside the cell, says Sorek, there would seem to be room for many more mistakes than researchers have actually observed.#p#分页标题#e#