Development of CRISPR-Cas13a-based antimicrobials capable of sequence-specific killing of target bacteria
Year: 2020
Type: article
Abstract: The emergence of antimicrobial-resistant bacteria is an increasingly serious threat to global health, necessitating the development of innovative antimicrobials. Here we report the development of a series of CRISPR-Cas13a-based antibacterial nucleocapsids, termed CapsidCas13a(s), capable of sequence-specific killing of carbapenem-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus by recognizing corresponding antimicrobial resistance genes. CapsidCas13a constructs are generated by packaging programmed CRISPR-Cas13a into a bacteriophage capsid to target antimicrobial resistance genes. Contrary to Cas9-based antimicrobials that lack bacterial killing capacity when the target genes are located on a plasmid, the CapsidCas13a(s) exhibit strong bacterial killing activities upon recognizing target genes regardless of their location. Moreover, we also demonstrate that the CapsidCas13a(s) can be applied to detect bacterial genes through gene-specific depletion of bacteria without employing nucleic acid manipulation and optical visualization devices. Our data underscore the potential of CapsidCas13a(s) as both therapeutic agents against antimicrobial-resistant bacteria and nonchemical agents for detection of bacterial genes.
Source: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,380
Funders: Massachusetts Institute of Technology, Takeda Science Foundation, Japan Agency for Medical Research and Development, Imperial College London, Ministry of Education, Culture, Sports, Science and Technology, Jichi Medical University, Mochida Memorial Foundation for Medical and Pharmaceutical Research, Medical Research Council, Japan Society for the Promotion of Science
Awards: Role of cGAS in bacterial virulence and antimicrobial resistance., Development of bacteriophage therapy for normalisation of bacterial flora and treatment of diseases., G3246125953, G3334138709, mecAを標的としたMRSAに対する抗菌ファージの開発, Integrated understanding of the beta-lactam resistant mechanisms in mutations responsible for the beta-lactam resistance in oxacillin susceptible MRSA, Development of target-specific bactericidal chimeric phages using a synthetic genome, G6168406386, Translational Research Initiative, Development of a novel antibacterial using bacteriophage and RNA targeting CRISPR system, G7059574175, Comprehensive transcriptome analysis of group A streptococci using the murine invasive model reveals a key gene network causing severe invasive diseases, The mechanism of spread of epidemic clones of antimicrobial resistant bacteria, G8302323029, Mechanism of persistent infection caused by genome rearrangement, 薬剤耐性菌に対する新規追尾型抗菌治療法の開発, Development of a chasing type antimicrobial using bacteriophage
OpenAlex ID: W3033658243