Development of CRISPR-Cas13a-based antimicrobials capable of sequence-specific killing of target bacteria
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Development of CRISPR-Cas13a-based antimicrobials capable of sequence-specific killing of target bacteria. / Kiga, Kotaro; Tan, Xin-Ee; Ibarra-Chávez, Rodrigo; Watanabe, Shinya; Aiba, Yoshifumi; Sato’o, Yusuke; Li, Feng-Yu; Sasahara, Teppei; Cui, Bintao; Kawauchi, Moriyuki; Boonsiri, Tanit; Thitiananpakorn, Kanate; Taki, Yusuke; Azam, Aa Haeruman; Suzuki, Masato; Penadés, José R; Cui, Longzhu.
In: Nature Communications, Vol. 11, 2934, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Development of CRISPR-Cas13a-based antimicrobials capable of sequence-specific killing of target bacteria
AU - Kiga, Kotaro
AU - Tan, Xin-Ee
AU - Ibarra-Chávez, Rodrigo
AU - Watanabe, Shinya
AU - Aiba, Yoshifumi
AU - Sato’o, Yusuke
AU - Li, Feng-Yu
AU - Sasahara, Teppei
AU - Cui, Bintao
AU - Kawauchi, Moriyuki
AU - Boonsiri, Tanit
AU - Thitiananpakorn, Kanate
AU - Taki, Yusuke
AU - Azam, Aa Haeruman
AU - Suzuki, Masato
AU - Penadés, José R
AU - Cui, Longzhu
PY - 2020
Y1 - 2020
N2 - Emergence of antimicrobial-resistant bacteria is an increasingly serious threat to global health, necessitating the development of innovative antimicrobials. We established a series of CRISPR-Cas13a-based antimicrobials, termed PhagoCas13a(s), capable of sequence-specific killing of carbapenem-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus through promiscuous RNA cleavage after recognizing corresponding antimicrobial resistance genes. PhagoCas13a constructs were generated by packaging CRISPR-Cas13a into a bacteriophage 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 PhagoCas13a(s) exhibited strong bacterial killing activities upon recognizing target genes regardless of their location. The antimicrobials’ treatment efficacy was confirmed using a Galleria mellonella larvae model. Further, we demonstrated that the PhagoCas13a(s) can assist in bacterial gene detection without employing nucleic acid amplification and optical devices. One Sentence Summary Novel gene-specific antimicrobials capable of killing drug-resistant bacteria and applicable to detect bacterial genes were developed.
AB - Emergence of antimicrobial-resistant bacteria is an increasingly serious threat to global health, necessitating the development of innovative antimicrobials. We established a series of CRISPR-Cas13a-based antimicrobials, termed PhagoCas13a(s), capable of sequence-specific killing of carbapenem-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus through promiscuous RNA cleavage after recognizing corresponding antimicrobial resistance genes. PhagoCas13a constructs were generated by packaging CRISPR-Cas13a into a bacteriophage 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 PhagoCas13a(s) exhibited strong bacterial killing activities upon recognizing target genes regardless of their location. The antimicrobials’ treatment efficacy was confirmed using a Galleria mellonella larvae model. Further, we demonstrated that the PhagoCas13a(s) can assist in bacterial gene detection without employing nucleic acid amplification and optical devices. One Sentence Summary Novel gene-specific antimicrobials capable of killing drug-resistant bacteria and applicable to detect bacterial genes were developed.
U2 - 10.1038/s41467-020-16731-6
DO - 10.1038/s41467-020-16731-6
M3 - Journal article
C2 - 32523110
VL - 11
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 2934
ER -
ID: 241528669