A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
Midbiotics : conjugative plasmids for genetic engineering of natural gut flora (2019)
Ruotsalainen, P., Penttinen, R., Mattila, S., & Jalasvuori, M. (2019). Midbiotics : conjugative plasmids for genetic engineering of natural gut flora. Gut Microbes, 10(6), 643-653. https://doi.org/10.1080/19490976.2019.1591136
JYU-tekijät tai -toimittajat
Julkaisun tiedot
Julkaisun kaikki tekijät tai toimittajat: Ruotsalainen, Pilvi; Penttinen, Reetta; Mattila, Sari; Jalasvuori, Matti
Lehti tai sarja: Gut Microbes
ISSN: 1949-0976
eISSN: 1949-0984
Julkaisuvuosi: 2019
Volyymi: 10
Lehden numero: 6
Artikkelin sivunumerot: 643-653
Kustantaja: Taylor & Francis
Julkaisumaa: Britannia
Julkaisun kieli: englanti
DOI: https://doi.org/10.1080/19490976.2019.1591136
Julkaisun avoin saatavuus: Avoimesti saatavilla
Julkaisukanavan avoin saatavuus: Osittain avoin julkaisukanava
Julkaisu on rinnakkaistallennettu (JYX): https://jyx.jyu.fi/handle/123456789/66340
Tiivistelmä
The possibility to modify gut bacterial flora has become an important goal, and various approaches are used to achieve desirable communities. However, the genetic engineering of existing microbes in the gut, which are already compatible with the rest of the community and host immune system, has not received much attention. Here, we discuss and experimentally evaluate the possibility to use modified and mobilizable CRISPR-Cas9-endocing plasmid as a tool to induce changes in bacterial communities. This plasmid system (briefly midbiotic) is delivered from bacterial vector into target bacteria via conjugation. Compared to, for example, bacteriophage-based applications, the benefits of conjugative plasmids include their independence of any particular receptor(s) on host bacteria and their relative immunity to bacterial defense mechanisms (such as restriction-modification systems) due to the synthesis of the complementary strand with host-specific epigenetic modifications. We show that conjugative plasmid in association with a mobilizable antibiotic resistance gene targeting CRISPR-plasmid efficiently causes ESBL-positive transconjugants to lose their resistance, and multiple gene types can be targeted simultaneously by introducing several CRISPR RNA encoding segments into the transferred plasmids. In the rare cases where the midbiotic plasmids failed to resensitize bacteria to antibiotics, the CRISPR spacer(s) and their adjacent repeats or larger regions were found to be lost. Results also revealed potential caveats in the design of conjugative engineering systems as well as workarounds to minimize these risks.
YSO-asiasanat: geenitekniikka; antibioottiresistenssi; plasmidit; enterobakteerit; suolistomikrobisto
Vapaat asiasanat: genetic engineering; ESBL carriage; conjugative plasmid; CRISPR editing; enterobacteria
Liittyvät organisaatiot
Hankkeet, joissa julkaisu on tehty
- Plasmidiriippuvaiset bakteriofagit: uusi keino taistella biofilmejä, pitkäaikaisia infektioita ja antibioottivastustuskyvyn leviämistä vastaan
- Jalasvuori, Matti
- Suomen Akatemia
OKM-raportointi: Kyllä
Raportointivuosi: 2019
JUFO-taso: 1