Fighting pathogenic bacteria can be as frustrating as being an early adopter of electronic gadgets. You grab the latest smart phone, and the following day leaks of the next generation are hitting the net.
The broad-spectrum nature of many antibiotics is partially to blame as they destroy our friendly bacteria and contribute to resistance.
Lucky for us, a team of braniacs at the Massachusetts Institute of Technology might have found a way to gain the upper hand in this arms race; the bad news is they can’t do anything about your phone contract.
RNA-guided nucleases (RGNs) such as CRISPR/Cas evolved as a prokaryotic adaptive immune defense against phage infections and other mobile elements. Robert Citorik and colleagues repurposed this system to target genes transferring drug resistance to pathogenic E.coli strains.
Delivering their “programmable antimicrobials” using bacteriophages, they effectively beat these microbes with there own weapons.
Here is how it works:
- Transformation of plasmid-borne RGNs targeting beta-lactam resistance genes reduces transformation efficiency by a 1000-fold
- Delivery by bacteriophages (ΦRGNs) efficiently reduces the amount of viable cells even in the absence of antibiotic selection
- ΦRGNs exhibited rapid killing of target cells, possibly due to co-harbored plasmid borne functions such as toxin-antitoxin systems
- The system enables “specific bacterial knockdowns” in complex bacterial co-cultures
After establishing the system in vitro, the researchers tested their “conditional-lethality devices” in an in vivo EHEC infection model. ΦRGNs significantly improved survival and were even more efficient than the antibiotic the strain was resistant to.
From these finding the researchers concluded that ΦRGNs could be a viable alternative treatment for infections with highly resistant bacteria.
To read all the infectious details grab your favorite electronic device and browse to Nature Biotechnology, September 2014.