Pentobra: New antibiotic kills persisters and biofilms. @CNSI_UCLA https://t.co/msYKZNNxNs @acsnano #nanobio
— Ben Libberton (@benlibberton) February 5, 2016
Pentobra is the name of a new antibiotic that that can kill persister cells.
I was surprised to hear this during a talk in sunny Los Angeles last week because I'd never heard of it before.
One of the inventors of Pentobra, Adrea Kasko described how she and her co-workers had re-engineered the aminoglycoside tobramycin to give it an antimicrobial peptide tail. I mean, of course they did, sticking two antimicrobial compounds together to make a more potent one had to be a good idea, right?
Well, I'm doing the group a bit of a disservice here. Kasko described how after testing the effect of hundreds of different peptides on bacterial membranes, they realised that there are certain peptide sequences that will illicit known physical responses from the bacterial membrane. The group then hypothesised that attaching these peptides to known antibiotics could improve their permeability, especially in less metabolically active cells such as persisters.
To test this they attached a peptide to tobramycin which is known to have reduced effectivity against persister strains. This new compound, Pentobra, was then tested on a number of different bacteria and showed enhanced killing of S. aureus and E. coli persisters. This effect was apparently more severe than if a combination of the peptide and tobramycin were administered, possibly because the cells were not permeabilised to the tobramycin as efficiently.
Due to the careful design, Pentobra is also completely non-toxic to a range of different eukaryotic cells.
Does Pentobra kill bacteria that are resistant to tobramycin? I don't know! This wasn't covered in the paper and I didn't get a chance to ask. It would be great if it did, however, targeting persister cells alone makes this a great discovery.
Of course, now that they have proved the concept there are many different possibilities for different peptides and drugs.
It would be interesting to see what the Nature Microbiology Community thinks. Pentobra seems to be more widely reported in the NanoTech literature than Bio so I don't think many people will have heard about it.
Here is a link to the paper in ACS Nano: