TY - JOUR
T1 - Anti-CRISPR prediction using deep learning reveals an inhibitor of Cas13b nucleases
AU - Wandera, Katharina G.
AU - Alkhnbashi, Omer S.
AU - Bassett, Harris v.I.
AU - Mitrofanov, Alexander
AU - Hauns, Sven
AU - Migur, Anzhela
AU - Backofen, Rolf
AU - Beisel, Chase L.
N1 - Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/7/21
Y1 - 2022/7/21
N2 - As part of the ongoing bacterial-phage arms race, CRISPR-Cas systems in bacteria clear invading phages whereas anti-CRISPR proteins (Acrs) in phages inhibit CRISPR defenses. Known Acrs have proven extremely diverse, complicating their identification. Here, we report a deep learning algorithm for Acr identification that revealed an Acr against type VI-B CRISPR-Cas systems. The algorithm predicted numerous putative Acrs spanning almost all CRISPR-Cas types and subtypes, including over 7,000 putative type IV and VI Acrs not predicted by other algorithms. By performing a cell-free screen for Acr hits against type VI-B systems, we identified a potent inhibitor of Cas13b nucleases we named AcrVIB1. AcrVIB1 blocks Cas13b-mediated defense against a targeted plasmid and lytic phage, and its inhibitory function principally occurs upstream of ribonucleoprotein complex formation. Overall, our work helps expand the known Acr universe, aiding our understanding of the bacteria-phage arms race and the use of Acrs to control CRISPR technologies.
AB - As part of the ongoing bacterial-phage arms race, CRISPR-Cas systems in bacteria clear invading phages whereas anti-CRISPR proteins (Acrs) in phages inhibit CRISPR defenses. Known Acrs have proven extremely diverse, complicating their identification. Here, we report a deep learning algorithm for Acr identification that revealed an Acr against type VI-B CRISPR-Cas systems. The algorithm predicted numerous putative Acrs spanning almost all CRISPR-Cas types and subtypes, including over 7,000 putative type IV and VI Acrs not predicted by other algorithms. By performing a cell-free screen for Acr hits against type VI-B systems, we identified a potent inhibitor of Cas13b nucleases we named AcrVIB1. AcrVIB1 blocks Cas13b-mediated defense against a targeted plasmid and lytic phage, and its inhibitory function principally occurs upstream of ribonucleoprotein complex formation. Overall, our work helps expand the known Acr universe, aiding our understanding of the bacteria-phage arms race and the use of Acrs to control CRISPR technologies.
UR - https://www.scopus.com/pages/publications/85134785223
U2 - 10.1016/j.molcel.2022.05.003
DO - 10.1016/j.molcel.2022.05.003
M3 - Article
C2 - 35649413
AN - SCOPUS:85134785223
SN - 1097-2765
VL - 82
SP - 2714-2726.e4
JO - Molecular Cell
JF - Molecular Cell
IS - 14
ER -