Researchers discover biological basis of'bacterial immune system'25 November 2009

Bacteria don't have easy lives. In addition tomammalian immune systems that besiege thebugs, they have natural enemies calledbacteriophages, viruses that kill half the bacteriaon Earth every two days.

Still, bacteria and another class of microorganismscalled archaea (first discovered in extremeenvironments such as deep-sea volcanic vents)manage just fine, thank you, in part because theyhave a built-in defense system that helps protectthem from many viruses and other invaders.

A team of scientists led by researchers at theUniversity of Georgia has now discovered how thisbacterial defense system works, and it could leadto new classes of targeted antibiotics, new tools tostudy gene function in microorganisms and morestable bacterial cultures used by food andbiotechnology industries to make products such asyogurt and cheese.

The research was published today in the journal Cell.

"Understanding how bacteria defend themselvesgives us important information that can be used toweaken bacteria that are harmful and strengthenbacteria that are helpful," said Michael Terns, aprofessor of biochemistry and molecular biology inUGA's Franklin College of Arts and Sciences. "Wealso hope to exploit this knowledge to develop newtools to speed research on microorganisms."

Other authors on the Cell paper include RebeccaTerns, a senior research scientist in biochemistryand molecular biology at UGA; Caryn Hale, agraduate student in the Terns lab at UGA; LanceWells, an assistant professor of biochemistry andmolecular biology and Georgia Cancer CoalitionScholar at UGA and his graduate student PengZhao; and research associate Sara Olson,assistant professor Michael Duff and associateprofessor Brenton Graveley of the University of

Connecticut Health Center.

The system, whose mechanism of action wasuncovered in the Terns lab (Michael and RebeccaTerns are a husband-wife team), involves a"dynamic duo" made up of a bacterial RNA thatrecognizes and physically attaches itself to a viraltarget molecule, and partner proteins that cut upthe target, thereby "silencing" the would-be cellkiller.

The invader surveillance component of the dynamicduo (an RNA with a viral recognition sequence)comes from sites in the genomes of bacteria andarchaea, known technically as "clustered regularlyinterspaced short palindromic repeats" or morefamiliarly called CRISPRs. (A palindrome is a wordor sentence that reads the same forward andbackward.) CRISPR RNAs don't work alone infighting invaders, though.

Their partners in invader defense are Cas proteinsthat arise from a suite of genes called "CRISPR-associated" or Cas genes. Together, they form the"CRISPR-Cas system," and the new paperdescribes this dynamic duo and how they protectbacteria from viruses.

"You can look at one as a police dog that tracksdown and latches onto an invader, and the other asa police officer that follows along and `silences' theoffender," said Rebecca Terns. "It functions like ourown immune system, constantly watching for andneutralizing intruders. But the surveillance is doneby tiny CRISPR RNAs rather than antibodies."

What the team discovered was that a particularcomplex of CRISPR RNAs and a subset of the Casproteins termed the RAMP module recognizes anddestroys invader RNAs that it encounters.

"This work has uncovered intriguing parallelsbetween the bacterial CRISPR-Cas system and thehuman immune system, suggesting a novel way to

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target disease-causing bacteria," said LaurieTompkins, Ph.D., who oversees geneticmechanisms grants at the National Institutes ofHealth's National Institute of General MedicalSciences. "It may be possible to turn CRISPR-Casinto a suicide machine, killing pathogenic bacteriaby an attack on their own molecules, similar to theself-destruction seen in human autoimmunediseases."

Understanding how the system silences invadersopens up opportunities to exploit it. So far,CRISPRs have been found in about half of thebacterial genomes that have been mapped orsequenced and in nearly all sequenced archaealgenomes. Such pervasiveness indicates that anability to manipulate the CRISPR-Cas system couldyield a broad range of applications. For example,using the knowledge that they have obtained in thiswork, the Terns now envision being able to designnew CRISPR RNAs that will take advantage of thesystem to selectively cleave target RNAs inbacterial cells.

"These could target viruses that wipe out cultures ofbacteria used by industry to produce enzymes,"said Michael Terns, "or could target the geneproducts of the bacteria themselves. With this set ofCas proteins, we now know how to cut a targetRNA at the site we choose."

"Believe it or not, we have only recently recognizedthat these microorganisms have a heritableimmune system [because it is so different from ourown]," added Rebecca Terns.

Remarkably, scientists are already in a position tobegin to capitalize on their rapidly growingknowledge of this bacterial immune system.

Source: University of Georgia (news : web)

APA citation: Researchers discover biological basis of 'bacterial immune system' (2009, November 25)retrieved 26 July 2018 from https://phys.org/news/2009-11-biological-basis-bacterial-immune.html

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