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.