How Viruses Disable Bacterial Immune Systems

“These anti-Crispr proteins keep the bacteria from recognizing the viral DNA,” Lander explained. He called these anti-Crispr proteins “exceptionally clever” because they appear to have evolved to target a crucial piece of the Crispr machinery. If bacteria were to mutate this machinery to avoid viral attacks, the Crispr system would cease to function. “Crispr systems cannot escape from these anti-Crispr proteins without completely changing the mechanism they use to recognize DNA,” he said.

Another anti-Crispr protein uses a different trick. Based on its location and negative charge, the researchers believe this anti-Crispr protein acts as a DNA mimic, fooling Crispr into binding this immobilizing protein, rather than an invading viral DNA.

“These findings are important because we knew that anti-Crispr proteins were blocking bacterial defenses, but we had no idea how,” said Lander. The researchers believe this new understanding of anti-Crispr proteins may eventually lead to more sophisticated and efficient tools for gene editing. Perhaps anti-Crispr proteins can be used in Crispr systems to swoop in to block gene editing—or researchers could degrade anti-Crispr proteins to trigger gene editing. “That might work as an on-off switch for Crispr,” Lander said.

In addition to Lander and Wiedenheft, the study, “Structure Reveals Mechanisms of Viral Suppressors that Intercept a Crispr RNA-Guided Surveillance Complex,” was led by first authors Saikat Chowdhury of TSRI and Joshua Carter of Montana State University. Other authors of the study were MaryClare F. Rollins, Sarah M. Golden, Ryan N. Jackson and Connor Hoffmann of Montana State University; Lyn’Al Nosaka of TSRI; Joseph Bondy-Denomy of the University of California, San Francisco; Karen L. Maxwell and Alan R. Davidson of the University of Toronto, Toronto, CA; and Elizabeth R. Fischer of the National Institutes of Health’s National Institute of Allergy and Infectious Diseases.

The study was supported by the National Institutes of Health (grants P20GM103500, P30GM110732-03, R01GM110270, Q1 R01GM108888, P20GM103474, F32 GM108436, DP2EB020402 and DP5-OD021344); the National Institutes of Health Intramural Research Program; the Canadian Institutes of Health Research (grant MOP-130482 and MOP-136845); the University of California, San Francisco, Program for Breakthrough Biomedical Research, funded in part by the Sandler Foundation; the National Science Foundation EPSCoR (grant EPS-110134); the M.J. Murdock Charitable Trust; and a young investigator award from Amgen. Lander is also supported as a Searle Scholar and Pew Scholar.

(ID:44610366)