
How to Kill Antibiotic-Resistant ‘Superbugs’ Without Antibiotics - Parbeyjr
http://edgylabs.com/2016/10/17/kill-antibiotic-resistant-superbugs-without-antibiotics/
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danielmorozoff
Whenever i see nano particles used to combat disease, I am always interested
in the off target controls. Since they are using physical mechanism to disrupt
membrane stability (in the case of bacteria), controlling targeting is very
difficult and requires vastly different membrane properties on the surface of
bacteria vs regular cells. Issues usually involve lodging of nano particles in
the liver or kidneys/ lysis and cytotoxicity . Here they looked at haemolytic
and necrotic activities in cells and assessed whether the mice survived- most
are short term, and aggregation of nano particles is not uncommon to cause
large obvious pathology, it just takes time.

I looked up the core molecule 'PAMAM' or Poly(amidoamine) and it seems to show
relatively low cytoxicity, but recent studies seem to shed some more light:

'More recently, a series of studies by Mukherjee et al.[13][14][15] have shed
some light on the mechanism of PAMAM cytotoxicity, providing evidence that the
dendrimers break free of their encapsulating membrane (endosome) after being
absorbed by the cell, causing harm to the cell's mitochondria and eventually
leading to cell death. Further elucidation of the mechanism of PAMAM
cytotoxicity would help resolve the dispute as to precisely how toxic the
dendrimers are.'

[0][https://en.wikipedia.org/wiki/Poly(amidoamine)#Toxicity](https://en.wikipedia.org/wiki/Poly\(amidoamine\)#Toxicity)

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gerbal
Have there been animal model tests of these particles?

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danielmorozoff
Seems so. Results are conflicting in terms of adverse effects. But seem to
show these particles cross into normal cells (neurons for example)/ some lead
to death some do not.

here is a quote though from one paper in mice at high concentrations: 'There
was no effect on other haematological parameters. Histopathological evaluation
of dendrimer-treated groups did not reveal any abnormalities in the low- and
medium-dose groups, but at a high dose level, toxicity was observed in the
liver and kidney.'

[http://rspa.royalsocietypublishing.org/content/466/2117/1535](http://rspa.royalsocietypublishing.org/content/466/2117/1535)

[http://pubs.acs.org/doi/abs/10.1021/mp300391v](http://pubs.acs.org/doi/abs/10.1021/mp300391v)

[https://www.ncbi.nlm.nih.gov/pubmed/27534577](https://www.ncbi.nlm.nih.gov/pubmed/27534577)

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anonymfus
Full article (illegal):

[http://www.nature.com.sci-
hub.ac/articles/nmicrobiol2016162](http://www.nature.com.sci-
hub.ac/articles/nmicrobiol2016162)

Please support Sci-Hub: [https://sci-hub.ac/donate](https://sci-hub.ac/donate)

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Dolores12
Illegal or not depends on your jurisdiction.

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akanet
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.

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

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jaggederest
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.

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todd8
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/](https://www.ncbi.nlm.nih.gov/m/pubmed/21271212/)

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

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todd8
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.

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btilly
Destroying diseases through biomechanical stress sounds cool. But my concern
would be whether the stress increases the mutation rate. As a well-known
example of another biomechanical stress that does so, consider asbestos.

I wouldn't want a treatment for my cold that could give me cancer in 20
years...

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mellavora
ummm. The cold is caused by a virus (rhinovirus, RSV, enterovirus, or
adenovirus) not bacteria.

Please don't take antibiotics to treat viral infections. The best you can hope
for is (measurable) damage to your own gut bacteria. The worst is breeding
more superbugs.

~~~
btilly
The common cold is indeed caused by a virus. However colds often result in
opportunistic bacterial infections, and a very large number of what people
call colds are caused by bacteria.

Therefore many (though certainly not all) colds are appropriately treated with
an antibiotic.

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sakopov
I know next to nothing about this stuff but is using antibiotics or the kind
of treatment outlined in this article prevent our body's natural defenses from
"learning" how to fight off these bacterias? Are we basically pumping our
bodies full of chemicals to the point that our immune system atrophies after
several generations?

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fucking_tragedy
> antibiotics prevent our body's natural defenses from "learning" how to fight
> off these bacterias

Unconstrained use of antibiotics allow bacteria's natural defenses to learn
how to stay alive in our bodies.

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josinalvo
In a bit more detail:

A bacterium does a series of chemical transformations to stay alive.

An antibiotic disrupts the bacteria lifecycle by interfering with such
transformations.

These transformations might be different across bacteria. As you have millions
of bacteria in an individual, some might suffer smaller results from the
antibiotic, and be 'not as disrupted'.

If you don't take the full dose of antibiotics, these 'not as disrupted'
bacteria might survive, make you sick again. And worse: the antibiotic will
have a harder time killing them.

Some of their 'children' will be more 'disruptable' then they are, some less,
but the average is less 'disruptable'.

Repeat the process many times, and you get bacteria that don't die with the
antibiotic :(

Nothing to do with your immune system, that creates its own kind of
'antibiotic'

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Senji
Are there substances to which in order to become resistant the bactria would
become vulnerable to something else.

If there are you could attack it with a coctail of two or three.

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pmontra
Basically they're shooting nano bullets to the bacteria and those bullets
can't be stopped. But how can they deliver those nano particles only to the
harmful bacteria? They should kill also the good ones.

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Madmallard
What about gut bacteria? Is that going to be destroyed?

Why aren't phages being researched?

Does this target mitochondria too? Other bacteriocidal antibiotics apparently
do so, because the structures are similar enough.

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Fomite
Phages are being researched. This literally comes up in every single HN thread
on antibiotics, so once more, posting my "Why Phages Aren't the Answer"
shortlist. Note that I _love_ phage therapy - this is the problems as seen by
someone who doesn't think it's a dead end:

Phage therapy is neat, it really is, but there are a couple major issues:

\- There is no such thing as a "broad spectrum" phage. You can't do empirical
treatment using phages, and there's not really "off the shelf" phage therapy -
it tends to be a bespoke creation for a particular infection.

\- There's some serious regulatory problems, similar to those experienced by
fecal transplant treatments. We're not yet really equipped to think about
handling evolving, custom microbes as a treatment. - Because of the first,
it's going to require a considerable amount more lab capacity than most
clinical settings currently have, and considerable delays until treatment.

\- There's also some biosafety issues around phage prep, but those are easily
solvable.

It's a great way to treat particularly resistant or hard to treat infections,
but it's not a particularly great general solution. There's a reason it was
abandoned in countries with easy access to antibiotics - they're just roundly
superior in basically every respect.

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vemv
Always wondered, would it possible to develop some kind of bacteria-fighting
nanobot technology?

Or would that be unrealistic as of 2016?

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known
Can it be used to kill Cancer cells?

