CRISPRi Used to Inhibit Multidrug Resistance in E. coli


Multidrug resistance (MDR) is whereby microorganisms acquire resistance to several antimicrobial agents. Therefore, it becomes harder to treat trivial infections as there are fewer and less effective treatment options available.


MDR can occur due to various reasons including mutations in the microorganisms, selective pressure, and gene transfer of resistance genes. Furthermore, the improper use of antimicrobials such as overuse, or not completing the course of drugs can also contribute to MDR. Therefore, there is a need to further develop antimicrobial drugs with novel targets.


A study published in Antimicrobial Agents and Chemotherapy showed that CRISPRi was able to suppress class 1 integron which is involved in the acquisition of MDR via gene transfer in E. coli.


E.coli strains were treated with CRISPRi technology which is CRISPR and dCas (dead Cas). CRISPRi can be used to downregulate gene expression instead of completely removing the gene via a knockout. Therefore, this type of CRISPR technology is reversible.


The E. coli strains treated with different CRISPR gRNA showed reduced expression in antibiotic resistance genes (dfrB2 cassette, sul1) and the integrase gene, IntI1. Furthermore, bacterial growth was inhibited upon antibiotic treatment compared to the controls. This increased susceptibility to antibiotics was due to blocking class 1 integron. Lastly, an assay showed that the rate of horizontal gene transfer had significantly reduced. Therefore, impairing the strain's ability to pass on antibiotic resistance genes.


This research could pave the way for a new type of antimicrobial drug with a novel mechanism.


References

1. https://aac.asm.org/content/early/2019/12/17/AAC.01789-19.abstract

2.https://www.niaid.nih.gov/research/antimicrobial-resistance-causes

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