Researchers have seen colistin-heteroresistant germs in the US | Hacker News Reader

Researchers have seen colistin-heteroresistant germs in the US

arstechnica.com

72 pointsrbanffy23 comments

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?

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.

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.

> histones are irrelevant, since prokaryotes don't have any

Good point :).

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...

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.

Prokaryotes actually do have histones! Or at least histone-like proteins. https://link.springer.com/article/10.1134/S0003683811060020

The simple answer is that no two individuals are subject to identical stimuli. The hard work is understanding what the relevant differences in stimuli are.

Genes are expressed in response to a signal, and no two bacteria in a population are ever receiving exactly the same signal, hence heterogeneity of gene expression.

Some bacteria have a "persistent" phenotype which means that they slow their metabolism way down, stop replicating and just hang out although they are genetically identical to the rest of the population. Normally (or in nutrient-rich conditions) this puts them at a disadvantage vs. the rest of the population, but in the event that there is an antibiotic compound the persisters survive way better. Persisters make up a very small percentage of the total population but can end up re-seeding the entire population after antibiotic treatment. It's not clear how the persister phenotype is regulated, so scientists often refer to it as stochastic. The really interesting thing is that persisters and non-persisters are genetically identical, and it's thought that maintaining some level of persisters in population is a bet-hedging strategy of the population.

*will edit with sources in a little bit

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

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.

It would revolutionize dentistry too! Imagine keeping all your healthy mouth biome and selectively eliminating cavity and gum disease bacteria.

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.

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 ...).

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.

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.medscape.com/slideshow/ten-new-antibiotics-60091...

http://www.bbc.com/news/health-43032602

> 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.antibioticresearch.org.uk/about-antibiotic-resis...

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.

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.

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

In many countries antibiotics (intended for human use) are sold over the counter.

I think in general the stuff that is resistant to multiple classes of antibiotics has mostly arisen from use that was not under a prescription (be it in countries with OTC sales, livestock or illicit use).

As someone who takes colistin regularly, this is frightening.

Out of curiosity, why do you take colistin regularly?

Reply on news.ycombinator.com