Rebooting Synthetic Phage-Inducible Chromosomal Islands: One Method to Forge Them All
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Rebooting Synthetic Phage-Inducible Chromosomal Islands : One Method to Forge Them All. / Ibarra Chávez, Rodrigo; Haag, Andreas F.; Dorado-Morales, Pedro; Lasa, Iñigo; Penadés, José R.
In: BioDesign Research, Vol. 2020, 5783064, 05.2020.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Rebooting Synthetic Phage-Inducible Chromosomal Islands
T2 - One Method to Forge Them All
AU - Ibarra Chávez, Rodrigo
AU - Haag, Andreas F.
AU - Dorado-Morales, Pedro
AU - Lasa, Iñigo
AU - Penadés, José R
PY - 2020/5
Y1 - 2020/5
N2 - Phage-inducible chromosomal islands (PICIs) are a widespread family of mobile genetic elements, which have an important role in bacterial pathogenesis. These elements mobilize among bacterial species at extremely high frequencies, representing an attractive tool for the delivery of synthetic genes. However, tools for their genetic manipulation are limited and timing consuming. Here, we have adapted a synthetic biology approach for rapidly editing of PICIs in Saccharomyces cerevisiae based on their ability to excise and integrate into the bacterial chromosome of their cognate host species. As proof of concept, we engineered several PICIs from Staphylococcus aureus and Escherichia coli and validated this methodology for the study of the biology of these elements by generating multiple and simultaneous mutations in different PICI genes. For biotechnological purposes, we also synthetically constructed PICIs as Trojan horses to deliver different CRISPR-Cas9 systems designed to either cure plasmids or eliminate cells carrying the targeted genes. Our results demonstrate that the strategy developed here can be employed universally to study PICIs and enable new approaches for diagnosis and treatment of bacterial diseases.
AB - Phage-inducible chromosomal islands (PICIs) are a widespread family of mobile genetic elements, which have an important role in bacterial pathogenesis. These elements mobilize among bacterial species at extremely high frequencies, representing an attractive tool for the delivery of synthetic genes. However, tools for their genetic manipulation are limited and timing consuming. Here, we have adapted a synthetic biology approach for rapidly editing of PICIs in Saccharomyces cerevisiae based on their ability to excise and integrate into the bacterial chromosome of their cognate host species. As proof of concept, we engineered several PICIs from Staphylococcus aureus and Escherichia coli and validated this methodology for the study of the biology of these elements by generating multiple and simultaneous mutations in different PICI genes. For biotechnological purposes, we also synthetically constructed PICIs as Trojan horses to deliver different CRISPR-Cas9 systems designed to either cure plasmids or eliminate cells carrying the targeted genes. Our results demonstrate that the strategy developed here can be employed universally to study PICIs and enable new approaches for diagnosis and treatment of bacterial diseases.
U2 - 10.34133/2020/5783064
DO - 10.34133/2020/5783064
M3 - Journal article
VL - 2020
JO - BioDesign Research
JF - BioDesign Research
M1 - 5783064
ER -
ID: 242718526