
Researchers have seen colistin-heteroresistant germs in the US - rbanffy
https://arstechnica.com/science/2018/03/scary-superbug-can-sneakily-dodge-last-resort-drug-and-we-dont-know-how/
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shock
_The researchers also sequenced the genomes of bacteria resisting colistin and
those susceptible to it. They were genetically identical.

Even though they have the same blueprints, they’re activating their genes
differently, Weiss says. It’s unclear how or why this happens._

I think that's the most interesting part of the article. Skip to that if you
want to save some time and don't need the background on antibiotic-resistant
bacteria.

It also highlights a misconception I had that genetically identical
individuals would express the same genes when subjected to the same
stimuli/conditions. Can someone with more knowledge share more details about
how gene expression works?

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_lpa_
The keyword to search for, if you are interested, is epigenetics. Modification
to e.g. histone protiens can change the expression of genes through a variety
of mechanisms. As far as I'm aware, exactly how this works isn't that well
understood.

~~~
rcthompson
Just a note: in this case, histones are irrelevant, since prokaryotes don't
have any. But more generally, protein binding, modification of bound proteins,
and methylation of the DNA itself are all epigenetic mechanisms that could be
in play here.

~~~
AstralStorm
To add to the list: activity of restriction enzymes, especially specific ones.

Colistin has a pretty interesting mechanism of action, disrupting ionic
balance in cell wall of lipopolysaccharide.

The mechanism of resistance may well be lucky upregulation of ionic balance
and cell wall stabilization proteins in response to the attack. Same as for
lysozyme.

This kind of ionic environment has wide ranging effects on cell metabolism so
changes genre expression. In multiple generations, the resistance might get
baked into the genome...

~~~
rcthompson
The OP says that the genome sequence hasn't changed. So in order to have that
persistent upregulation without any change in the genome sequence, you (most
likely) need an epigenetic mechanism to explain it.

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filoeleven
It’s long past time for the west to start looking seriously into phage
therapy, which Russia has been using for decades. Find the virus that targets
the bacteria you want gone, and let it do the hard work for you.

[https://en.m.wikipedia.org/wiki/Phage_therapy](https://en.m.wikipedia.org/wiki/Phage_therapy)

~~~
tensor_rank_0
last year I read that they have two major innovations in this field: 1. they
can use a t4 bacteriophage to deploy an arbitrary genetic payload and 2. they
can alter the "hooks" on the t4 to make it attach to a large variety of cells.

together, these discoveries pave the way to much more precise genetic
engineering.

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inglondon
_They’re members of a notorious family of multidrug-resistant pathogens,
called carbapenem-resistant Enterobacteriaceae (CRE), which collectively have
mortality rates as high as 50 percent and have spread rapidly around the globe
in recent years. A 2013 report by the Centers for Disease Control and
Prevention estimated that there were more than 9,300 CRE infections in the US
each year, leading to 600 deaths._

Is it correct to assume that while CREs have up to 50% mortality rate
worldwide, the US mortality rate of CRE infections is around 6.5%?

Edit: I applaud efforts to increase access to healthcare worldwide. We really
need to do more to combat the spread of such bacteria through better
management of antibiotic use, mainly in agriculture.

~~~
Retric
No, it's like saying shark attacks have up to 50% mortality rate (Great
Whites) with the average rate for all sharks being 6.5% (Hammerhead and Great
White and ...).

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Rotdhizon
It's of no surprise, we've long been warned that we are in for a drug-
resistant germ catastrophe in the coming decades.There's already strains of
some infections that are extremely resistant to all known forms of medication.
The biggest problem being that the advancement in the medical field for
developing new cures is minimal. We're re-using the same anti-biotics and
anti-x solutions for everything. Unless there are major medical breakthroughs
in the next 20 years, we are expected to see complete anti-biotic resistance
strains emerge.

~~~
JBReefer
That's a popular, but untrue, idea. There is a ton of research into new
antibiotics, and new classes of antibiotics. We just didn't need to until
recently.

[https://www.telegraph.co.uk/science/2016/03/14/first-new-
ant...](https://www.telegraph.co.uk/science/2016/03/14/first-new-antibiotic-
in-30-years-discovered-in-major-breakthroug/)

[https://www.medscape.com/slideshow/ten-new-
antibiotics-60091...](https://www.medscape.com/slideshow/ten-new-
antibiotics-6009164)

[http://www.bbc.com/news/health-43032602](http://www.bbc.com/news/health-43032602)

~~~
tensor_rank_0
> That's a popular, but untrue, idea. There is a ton of research

my microbiology professor said it is true. several major antibiotic companies
have shut down their antibiotics research program because the economics of
antibiotics are fucky.

[https://www.medpagetoday.com/infectiousdisease/generalinfect...](https://www.medpagetoday.com/infectiousdisease/generalinfectiousdisease/24708)

[https://www.antibioticresearch.org.uk/about-antibiotic-
resis...](https://www.antibioticresearch.org.uk/about-antibiotic-resistance/)

~~~
kpil
It wouldn't be particularily expensive for USA or EU, to fund research or
create economical incentives for commercial initiatives.

You could say that it might even be the very purpose for which democratic
states exists; to protect it's people.

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MindTooth
Can these resistant bacterias be credited to excessive prescriptions of
antibiotics by doctors?

As I have come to understand, is that some countries they prescribe antibiotic
for the smallest thing. In Norway that is not he case. I have the assumption
that you need to be really sick to get any.

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minikites
My understanding is that most of it is due to overuse of antibiotics in
livestock, due to the sheer scale.

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enthd
As someone who takes colistin regularly, this is frightening.

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telchar
Out of curiosity, why do you take colistin regularly?

