Scientists engineer a powerful new weapon against antibiotic-resistant bacteria

[Headhumpy]

https://www.sciencemag.org/news/2018/09/scientists-engineer-powerful-new-weapon-against-antibiotic-resistant-bacteria

The writeup from C&EN is somewhat more detailed but it may be paywalled:

https://cen.acs.org/pharmaceuticals/antibiotics/Aryl-compound-attacks-Gram-negative/96/i37

And here is the paper itself:

https://www.nature.com/articles/s41586-018-0483-6

I haven't had time to read it yet but it looks very interesting, a novel target inhibited by a novel mechanism.

[Da Space Core]

In essence this shows a possible new attack vector into gram negative bacteria, which is great. The question now is could this method be used for treatment in animals and people safely

[Genkaz]

Not sure what the big deal with anti biotic resistant bacteria is, all they need is a pair of really small pliers to rapidly fish out all of the cells.

[ConcreteBath]

The particular enzyme they're trying to inhibit has been targeted before in gram positive bacteria, but was thought to be impossible with gram negative bacteria. Gram negative bacteria have a "double layered" cell membrane that prevents the class of drug that this is based off of, arylomycins, from slipping past. These guys took these antibiotics and change the structure around a bit and found out that it was using a novel membrane transport mechanism. Same target, different route. Nice thing about that particular target is that it's unique to bacteria, i.e., it's harmless to us. This particular drug has shown a really high binding affinity towards that enzyme, and is a suicide inhibitor. It disables it's target permanently and that's it. Most problems with it are problems common to all antibiotics, i.e. increasing MDR disease, gut flora genocide.

Interestingly enough, this may be an example of "self promoted uptake", wherein the antibiotic initiates its own passage through the membrane. Being such a large and polar antibiotic, you'd usually have a difficult time getting across the membrane, but apparently whacking an extra positive charge in there makes all the difference.

[Shirt.]

What is this safety nonsense! Get the Howie coats, bright lights, microscopes, people openers and go vesalius on these super bugs!

[Headhumpy]

The mechanism of inhibition is the most surprising for me: amidine formation with the lysine residue of the Ser/Lys catalytic dyad rather than serine. Now I'm wondering whether this strategy can be used against other bacterial targets. Interestingly this antibiotic could have synergistic effects thanks to its inhibition of protein secretion. beta-Lactamases for example are secreted into the periplasmic space and inhibition of their secretion pathways could increase susceptibility to beta-lactam antibiotics.

[Revenge282]

https://youtu.be/Ac7G7xOG2Ag

I concur.

[Vuu]

Bacteriophage still superior

[notgeogzm]

What was ever wrong with some apple cider vinegar and an old sieve?

[Da Space Core]

bacteria evolve and can build resistance to our treatments. the more routes we have to eradicate them the better

[chipsnapper]

It took them 75 years or so, are we sure this will last just as long or longer?