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CRISPR used to kill bacteria without antibiotics

10 September 2018
Appeared in BioNews 966

A new approach to kill bacteria has been developed using genome editing, bypassing the need for antibiotics.

Researchers at the University of Colorado, Boulder, edited the genome of the bacteria E. coli to manipulate the expression of several genes. This multi-pronged attack debilitated the bacterium by putting it under increasing levels of stress within the cell.

As study author Dr Anushree Chatterjee explained to Quartz: 'If there's a person and if I just tug on their hair, they are a little pissed. But if I start tugging other areas – their coat and their shirt – they might lose it.'

By tugging on the expression of many different genes, the E. coli did indeed lose their ability to adapt and survive.

Dr Chatterjee's team has called this method developed Controlled Hindrance of Adaptation of Organism (CHAOS). The technique began when they were using genome editing to change the expression of just one gene at a time in E. coli, in search of a cellular switch that could be used to kill the bacterium.

However, when the researchers focused on one target at a time, the bacteria could cope, much as they do when they are exposed to an antibiotic. E. coli's ability to adapt fell away when they widened out their targets.

'We saw that when we tweaked multiple gene expressions at the same time – even genes that would seemingly help the bacteria survive – the bacteria’s fitness dropped dramatically,' said Peter Otoupal, a graduate student at the University of Colorado, Boulder, and also an author of the study.

The precise genes whose expression was altered did not seem to matter a great deal, the authors noted. Unlike antibiotic drugs, which often target an essential gene for a bacteria's survival, the CHAOS method instead seemed to rely on ramping up general background stress in the cell as several genes were tweaked out of optimal expression.

However, the authors intend to develop the technique further by finding the most efficient combination of genes to kill E. coli with CHAOS.

'We are running out of antibiotics and the very important problem is that we don’t have any new classes of antibiotics coming up,' said Dr Chatterjee. The researchers hope that CHAOS could eventually become an alternative to traditional antibiotics.

The study was published in the journal Communications Biology.

How to stop an antibiotic-resistant superbug
University of Colorado, Boulder |  3 September 2018
Multiplexed deactivated CRISPR-Cas9 gene expression perturbations deter bacterial adaptation by inducing negative epistasis
Nature Communications Biology |  3 September 2018
Scientists are using chaos to try and beat E. coli
Quartz |  6 September 2018
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