Comment by akanet | Hacker News Reader

Comment by akanet | Hacker News Reader

Looks like they found a way to generate nanoparticles that don't damage host cells, but target bacteria more or less exclusively:

  These star nanoparticles were termed ‘structurally nanoengineered
  antimicrobial peptide polymers’ (SNAPPs). Unlike existing selfassembled
  antimicrobial macromolecules, which will dissociate to
  unimers below their critical micelle concentration, SNAPPs
  are stable unimolecular architectures up to infinite dilution. We
  demonstrate that SNAPPs exhibit superior antibacterial activity
  against a range of clinically important Gram-negative bacteria,
  possess high therapeutic indices and display selectivity towards
  pathogens over mammalian cells.

More on biocompatibility with humans:

  As a test of biocompatibility, the haemolytic activities of SNAPPs
  were investigated by incubating them with red blood cells at different
  nanoparticle concentrations. Both S16 and S32 had negligible
  haemolytic activity. Even at a very high concentration of >100 × MBC,
  the extent of haemolysis was well below 30%. Subsequently, we
  investigated the viability of two types of mammalian cells (human
  embryonic kidney cells and rat hepatoma cells) in response to SNAPPs.
  The therapeutic indices (TI) of SNAPPs ranged from 52 to 171 ,
  generally higher than the TI of colistin, which is currently being
  used as the last therapeutic option for MDR Gram-negative pathogens

Very promising stuff. Even though this was built as a treatment for gram-negative bacteria, it seems to show an effect for gram-positive bacteria, too. Equally promising is how uniformly effective SNAPPs seemed to be across several types of gram-negative bacteria.

there's no reason to think that bacteria couldn't evolve resistance to these things, too.

Vacuoles would probably be a good solution, or some means of transport back out of the cell, and both would probably be minor modifications of existing systems in bacteria. I wonder if either would increase the stress on the host as well.

bacteria don't typically have vacuoles.

You're right, my bad.

true, but the article suggests that they were not seeing evidence of emergent resistance.

Also, the mechanism of action is one which bacteria would have a very hard time learning resistance to.

I'll believe it when they make a megaplate with that stuff.

megaplate: https://player.vimeo.com/video/180908160

> true, but the article suggests that they were not seeing evidence of emergent resistance.

It's a bit early for that, isn't it? Give it a decade or two of widespread use, and then we'll see.

> Also, the mechanism of action is one which bacteria would have a very hard time learning resistance to.

That is hopeful. But how hard is "a very hard time"? It takes decades? Centuries? Or never?

It's pretty trivial to generate resistance phenotypes in a lab at much shorter time scales to detect if it's possible.

It would seem very hard as the main mechanism of action for these nano particles is electrostatic pore formations- confirmed by their mechanistic studies.

This would require evolution of the outer membrane (OM), quite a big change for a bacteria to evolve. That said it's very surprising there are so few off target effects.

To some degree there are things that are "resistance proof", in that forming resistance to them would defacto leave organisms unable to survive in the human body.

A good example is highly acid/basic environments, thermal stress, or alcohols and solvents.

Anything that can reproduce in a 50 degree C alcohol bath, for example, is going to have a tough time adapting to humans well enough to be pathogenic.

These polymers might be a similar phenomenon, but that would also imply that they're inimical to humanity too, though perhaps at a higher concentration.

Don't forget prions. They survive temperatures above 120C and also alcohol and remain infectious. (Hydrogen peroxide and alkalis seem too work, but see [1] because I really know nothing of the science of sterilization.)

[1] https://www.ncbi.nlm.nih.gov/m/pubmed/21271212/

Prions aren't alive, by the same measure asbestos is also resistant.

Prions, like viruses, reproduce when inside a host. Parasites, bacteria, fungi, viruses and prions are all types of pathogens.

Sterilization protocols need to be followed to ensure that one patients prions don't infect another surgery patient. It turns out that relatively recent concerns over transmissible spongiform encephalopathy, caused by prions, has required changes to the sterilization procedures used in hospitals.

the fact that the polymers don't kill the mammalian cells means that whatever mammalian cells do to avoid destruction can be adapted by bacterial cells for their survival.

Except that there are fundamental differences between bacterial cells and mammalian cells that we can exploit which are extremely unlikely to change.

For example, nearly all antibiotics and antifungals target cell walls - a clear distinction that mammalian cells lack.

That's not true. Antifungals target ergosterol, which is a cell membrane compound (fungal cholesterol). Also the side effects are likely due to the similarities between ergosterol and cholesterol.

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