Syndicate content

NAR “Breakthrough Article” Describes Details of Antibiotic Resistance to CRISPR-Induced Disruption of Mobile Genetic Elements; IncC Conjugative Plasmids & SXT/R391 Elements Repair Double-Strand Breaks Caused by CRISPR–Cas During Conjugation

In a “Breakthrough Article” published on June 18, 2020 in Nucleic Acids Research (NAR), a group of scientists in the Département de Biologie, Université de Sherbrooke in Quebec (Canada) led by Vincent Burrus, PhD, has described how certain conjugative plasmids (that promote mobilization and transfer of antibiotic-resistance genes between bacterial strains and species) evade the degradative mechanisms of CRISPR defense systems. “Breakthrough Articles” at NAR describe studies that solve a long-standing problem in their field or provide exceptional new insight and understanding into an area of research that will clearly motivate and guide new research opportunities and directions. They represent the top papers that NAR receives for publication and are selected by the Editors based on nominations by authors and/or reviewers, and on the subsequent recommendation of the reviewers and editorial board members. This open-access “Breakthrough Article” article is titled “IncC Conjugative Plasmids and SXT/R391 Elements Repair Double-Strand Breaks Caused by CRISPR–Cas During Conjugation.” Antibiotic-resistance genes are mainly transmitted by integrative and conjugative elements (ICEs), and conjugative plasmids, but also by bacteriophages. Although bacteria have evolved defense mechanisms against such invaders (including CRISPR-Cas and Restriction-Modification systems), mobile genetic elements have also evolved diverse strategies to overcome these barriers. In this manuscript, the authors demonstrate that drug resistance-associated Incompatibility group C (IncC) conjugative plasmids and SXT/R391 ICEs are resilient against damage caused by CRISPR-Cas during entry into a new host by conjugation. A conserved locus of five genes appears to be involved in CRISPR and restriction evasion, including two genes that encode homologues of the Redβ (Syn) and λ Exonuclease (Exo) proteins from bacteriophage λ and that promote double-strand break repair by using short repeat sequences. The CRISPR and restriction evasion genes described in this study are conserved in IncA, IncC, IncT, IncP-7 and untyped conjugative plasmids, as well as SXT/R391 ICEs.

This manuscript highlights a novel mechanism of CRISPR-Cas evasion that does not rely on blocking Cas endonuclease activity. It also characterizes the biological function of Redβ/λ Exo homologues encoded by a wide range of mobile genetic elements, including conjugative plasmids, ICEs, and lambdoid bacteriophages.

Several investigators and editors who evaluated this manuscript nominated it for breakthrough status, stating “the discovery that the Syn-Exo systems may have at least in part evolved as anti-CRISPR proteins is quite profound” and expand our understanding of “a group of plasmids that are known to have a broad host range and that are particularly important in spreading resistance.”

Dr. Burrus’s laboratory at Université de Sherbrooke investigates the molecular mechanisms contributing to exchanges of genetic material between bacteria (horizontal gene transfer) and the impact of these exchanges on the evolution of microbial genomes. The lab’s models are mobile genetic elements that are responsible for the dissemination of antibiotic-resistance genes in Vibrio cholerae and Enterobacteria.

NUCLEIC ACIDS RESEARCH & BREAKTHROUGH ARTICLES

Nucleic Acids Research (NAR) is a publication of Oxford University Press and is fully open-access.Its mission is to provide outstanding, scientist-led evaluation and dissemination of the highest-caliber research across a wide range of disciplines focused on the role of nucleic acids and nucleic acid interacting molecules in cellular and molecular biology.

“Breakthrough articles” at NAR describe studies that solve a long-standing problem in their field or provide exceptional new insight and understanding into an area of research that will clearly motivate and guide new research opportunities and directions. They represent the top papers that NAR receives for publication and are selected by the Editors based on nominations by authors and/or reviewers, and on the subsequent recommendation of the reviewers and editorial board members.

[Nucleic Acids Research "Breakthrough Article"]