We are in desperate need of antibiotic-sparing approaches to antibacterial therapy. Antibiotic resistance is increasing, and we are becoming increasingly aware of the impact of antibotics on the microbiota. I blogged a while ago about CRISPR-Cas systems being used to tackle antibiotic-resistant bacteria on surfaces. But the same approach could be applied to treating human infections.
A study in Nature Biotechnology describes the development and testing of a CRISPR-Cas system to perform a “surgical strike” against antibiotic resistant staphylococci. The previous CRIPR-Cas approach, was a 2-step process: a temperate phage delivered the CRISPR-Cas system, and a lytic phage “mop up” any cells that missed out on the lytic phage. The approach in the current study was different, using a single step ‘phagemid’ to deliver the CRISPR-Cas system, which was lethal to the cell. Phagemids are bacteriophages that have been modified to carry a particular phage, and they do not co-replicate with the cells once infected.
Whilst the study showed some pretty impressive in vivo results in a S. aurues mouse skin model, the use of a phagemid to deliver the CRISPR-Cas system means that it will be difficult to reach 100% coverage for delivery of the CRISPR-Cas system. Furthermore, even if coverage was 100% effective and the CRISPR-Cas “surgical strike” took out all the antibiotic-resistant bacteria, the antibiotic-susceptible bacteria would still be there at the site of the infection. This probabaly precludes this approach as a stand-alone method to treat infection. However, this use of CRISR-Cas could be a a useful potential adjuvant to other more conventional approaches, or a way to shift the ratio of antibiotic-resistant : antibiotic-susceptible bacteria and effectively decolonise a carrier of antibiotic-resistant bacteria. This could be especially useful for gut colonisation with resistant Gram-negative bacteria (especially CPE), for which there are currently no effective decolonisation approaches.
Image: Wikimedia.
Reflections on Infection Prevention and Control 
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New Orizons Jon Thanks.
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Dear Jon,
This can be a very interesting approach to get rid of plasmids that can be shared by related species (for instance harmless E. coli and harmfull Klebsiella), provided that the phages can infect all relevant species.
How specific are these phages?
Would also be very interesting to see evolutionarily speaking what would happen: would the plasmids then go to other (phage resistant) species? Would phage resistant species evolve among E. coli?
Keep up the good work!
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These phages are as specific as any other – which is very. This is a strength and a limitation. It means you can really zoom into a specific species or even sub-species of interest, but also makes phage resistance more likely to develop. So yes, I do think the prospect of phage resistance is very real. I wonder whether a different delivery system for CRISPR-Cas systems would be better.
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