Скачать или смотреть Ending the pandemic of antibiotic resistance. Aotearoa Gaming Trust Scholar, Daniel Vallabhjee

Ending the pandemic of antibiotic resistance: Identifying the sRNA regulation of CRISPR-Cas to target resistance plasmid uptake.

Antibiotic resistant infections occur in the millions annually. The Fineran lab at the university of Otago is researching the regulation of CRISPR-Cas, a system that not only prevents viral infection of bacteria, but also regulates the spread of antibiotic resistance.

The number of infections resulting from antibiotic resistant bacteria is greatly increasing and spreading to different bacterial species. In the United States alone there are 2.8 million cases of antibiotic resistant infections annually, resulting in 35’000 deaths. Regulation of the uptake of antibiotic resistance genes is partially mediated by CRISPR-Cas.

CRISPR-Cas is a bacterial immune response that can recognize bacterial viruses, known as a phage, and develop an adaptive-like immune response against them. When a phage injects its genomic material into a host, the CRISPR-Cas system is able to acquire a small section of this genomic material known as a spacer and put it in a CRISPR array. When the phage infects a bacteria again this spacer is expressed as RNA and used by Cas proteins to recognize and degrade the viral genome.

Uptake of DNA that’s not part of the chromosome, some being plasmids, is commonly used to spread helpful genes around and are also regulated by CRISPR-Cas. The transfer of genes directly between bacteria via plasmids, known as conjugation, is the most common way antibiotic resistance spreads. Because CRISPR-Cas must both let some plasmids in and keep viruses out, it is tightly regulated to have a good balance of defense and gene acquisition.

Recent preliminary results from the Fineran lab have identified several small noncoding RNAs (sRNAs) that may be regulating CRISPR-Cas, and hence have an influence on plasmid uptake. We aim to identify which of these sRNAs regulate CRISPR-Cas activity and how they change the activity of the CRISPR-Cas system. Because changing the activity of the CRISPR-Cas system can change the uptake of antibiotic resistance plasmids, this project may identify novel drug targets to aid in the fight against antibiotic resistance.