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Author Topic: SCIENCE, Gravitational waves, and the whole LIGO OST!  (Read 512881 times)

scrdest

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Re: SCIENCE, Gravitational waves, and the whole LIGO OST!
« Reply #4350 on: September 30, 2016, 05:33:05 am »

They kind of can. There are resistance mechanisms that are only expressed in the presence of the relevant antiobiotic.
Expressed. Herein lies the rub.

Coming back to the car analogy, you don't need to have brakes working constantly to prevent you crashing into something - that would be an unnecessary tax on your car's performance, you can engage them on the fly when needed and keep them disengaged when not - but you need to have installed the brakes in the car before you started driving it somewhere.

Similarly, the resistance mechanism needs to show up in the genome, even if it is not part of the transcriptome 24/7.

There is one caveat, in that bacteria love to open source the resistances and so if you already *have* a resistant bacterium somewhere, the resistance may spread faster and further than it could by division of the parent strain alone and it can happen on the fly, with some limitations - but you need to get the OG bacterium in the first place.
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Re: SCIENCE, Gravitational waves, and the whole LIGO OST!
« Reply #4351 on: September 30, 2016, 08:07:15 am »

Yeah, I recall reading about some of the theories on multicellular emergence being shaken up when bacteria were found swapping out hardware from others.
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Sheb

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Re: SCIENCE, Gravitational waves, and the whole LIGO OST!
« Reply #4352 on: September 30, 2016, 08:19:55 am »

Yeah, the issue ofc is that most of our antibiotics are molecules we got from bacteria and their derivatives (Streptomyces alone account for a majority I think), so the resistance mechanisms ARE out there, either in the producing bacteria (which obviously need to be resistant) or in bacteria living alongside it.
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scrdest

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Re: SCIENCE, Gravitational waves, and the whole LIGO OST!
« Reply #4353 on: September 30, 2016, 09:24:04 am »

Yeah, the issue ofc is that most of our antibiotics are molecules we got from bacteria and their derivatives (Streptomyces alone account for a majority I think), so the resistance mechanisms ARE out there, either in the producing bacteria (which obviously need to be resistant) or in bacteria living alongside it.
That's not entirely true. First, you're forgetting the very first antibiotic being fungal, and the whole group of penicillins and cephalosporins and the like. This is not denying a lot is bacterial, but penicillin is also the very first antibiotic where widespread resistance popped up and it is not a bacterial product.

Second, you're ignoring that bacteria are not a homogenous group. Unless you look at very wide-spectrum antibiotics, a G- bacteria will simply not be susceptible to G+ bacteria's antibiotics, and vice-versa, and that's not getting into smaller-scale differences. They don't need specific resistances, the molecular target of the antibiotic simply isn't there, not even by a long shot. It doesn't work on the producer, but to say it is resistant is misleading.

Third, a huge chunk of modern antibiotics are not the same substances microorganisms produce in the wild. They are synthetic or semi-synthetic, and only based on the original molecule, with altered action - for example, 2nd-onwards generations of cephalosporins act stronger on G-, sometimes at the expense of the effect on G+, compared to gen 1.
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ChairmanPoo

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Re: SCIENCE, Gravitational waves, and the whole LIGO OST!
« Reply #4354 on: September 30, 2016, 03:06:04 pm »

You don't have to go for heavy artillery to find antibiotics that target both. You pointed one out yourself in your example (cephalosporins). In fact, the most commonly used antibiotics do, in fact, target both Gram + and - bacteria.
« Last Edit: September 30, 2016, 03:15:40 pm by ChairmanPoo »
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Helgoland

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Re: SCIENCE, Gravitational waves, and the whole LIGO OST!
« Reply #4355 on: September 30, 2016, 06:58:52 pm »

the very first antibiotic being fungal
Arsphenamine and the sulfonamides beg to differ.
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Re: SCIENCE, Gravitational waves, and the whole LIGO OST!
« Reply #4356 on: October 01, 2016, 05:07:45 am »

Yeah, the issue ofc is that most of our antibiotics are molecules we got from bacteria and their derivatives (Streptomyces alone account for a majority I think), so the resistance mechanisms ARE out there, either in the producing bacteria (which obviously need to be resistant) or in bacteria living alongside it.
That's not entirely true. First, you're forgetting the very first antibiotic being fungal, and the whole group of penicillins and cephalosporins and the like. This is not denying a lot is bacterial, but penicillin is also the very first antibiotic where widespread resistance popped up and it is not a bacterial product.

Second, you're ignoring that bacteria are not a homogenous group. Unless you look at very wide-spectrum antibiotics, a G- bacteria will simply not be susceptible to G+ bacteria's antibiotics, and vice-versa, and that's not getting into smaller-scale differences. They don't need specific resistances, the molecular target of the antibiotic simply isn't there, not even by a long shot. It doesn't work on the producer, but to say it is resistant is misleading.

Third, a huge chunk of modern antibiotics are not the same substances microorganisms produce in the wild. They are synthetic or semi-synthetic, and only based on the original molecule, with altered action - for example, 2nd-onwards generations of cephalosporins act stronger on G-, sometimes at the expense of the effect on G+, compared to gen 1.



Sure, I said most, not all. Wiki tells me that 2/3rd of all natural antibiotics used come from Streptomyces. As for the b-lactams, they're fungal, but the resistance was already out there in bacterias before we used them. The resistants bacterias didn't invent a new hydrolase, they just made use of what was already there.
And even if they're semi-synthetic, they're still close enough to wild-type antibiotics that it's not much work for existing enzymes that degrade the wild-type antibiotic to evolve to be able to degrade the variant. See, cephalosporins and all other b-lactams derivatives.

I mean, no offense but I'm kinda doing my PhD on carbapenemases. :D
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scrdest

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Re: SCIENCE, Gravitational waves, and the whole LIGO OST!
« Reply #4357 on: October 01, 2016, 06:58:41 am »

You don't have to go for heavy artillery to find antibiotics that target both. You pointed one out yourself in your example (cephalosporins). In fact, the most commonly used antibiotics do, in fact, target both Gram + and - bacteria.
Uh, what exactly are you responding to? I never said wide-spectrums don't real, I just pointed out that narrow-spectrum antibiotics exist, and so natural antibiotic producers don't necessarily need to be resistant.

the very first antibiotic being fungal
Arsphenamine and the sulfonamides beg to differ.
Fair enough, I didn't specify what rules I was going by: Protonsil was discovered in 1932, so later than Penicillin, though it was marketed earlier, so by actual availability it has primacy. Arsphenamine is not usually counted as an antibiotic for, upon some research, weird reasons.

Sure, I said most, not all. Wiki tells me that 2/3rd of all natural antibiotics used come from Streptomyces. As for the b-lactams, they're fungal, but the resistance was already out there in bacterias before we used them. The resistants bacterias didn't invent a new hydrolase, they just made use of what was already there.
And even if they're semi-synthetic, they're still close enough to wild-type antibiotics that it's not much work for existing enzymes that degrade the wild-type antibiotic to evolve to be able to degrade the variant. See, cephalosporins and all other b-lactams derivatives.

I mean, no offense but I'm kinda doing my PhD on carbapenemases. :D
All the more reason to try to argue then, better me than the reviewer :P

I didn't actually know there was a resistance in the wild, how do we know that's the case? And one way or another, unless you're somehow both a bio grad and creationist I suppose, they did invent a new hydrolase, the only question is when.

Unless I massively misremembered, I think you're wrong on the topic of (semi-)synthetics. I recall watching a video on topic of antibiotic resistance (I think it was a part of an intro to a vid about teixobactin maybe) that showed the arms race between beta-lactamases and beta-lactam modifications preventing lactamase cleavage of the ring. But unfortunately that was shown in class, like two years ago, so I might be spectacularly wrong here. I didn't research it just now, I'll check later.
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Dozebôm Lolumzalìs

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Re: SCIENCE, Gravitational waves, and the whole LIGO OST!
« Reply #4358 on: October 01, 2016, 09:06:51 am »

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« Last Edit: October 01, 2016, 09:23:01 am by Dozebôm Lolumzalìs »
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Re: SCIENCE, Gravitational waves, and the whole LIGO OST!
« Reply #4359 on: October 01, 2016, 09:20:54 am »

Well, you stated
Quote
Unless you look at very wide-spectrum antibiotics a G- bacteria will simply not be susceptible to G+ bacteria's antibiotics, and vice-versa
Which seems to imply that  you have to look for unusual drugs in order to achieve this. I was merely pointing out that it is not that infrequent.
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Sheb

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Re: SCIENCE, Gravitational waves, and the whole LIGO OST!
« Reply #4360 on: October 01, 2016, 10:07:48 am »

Well, for the penicillins for exemple we can do phylogenetic analysis of the b-lactamases and see that they evolved long before the widespread human use of antibiotics.

I think the point I was trying to make was that since most of our antibiotics are either natural molecules or their derivatives, resistance can spread very quickly, because the means to resist it have either already evolved, or need only slight modifications from the resistance mechanism used against the molecule the antibiotic is derived from.
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scrdest

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Re: SCIENCE, Gravitational waves, and the whole LIGO OST!
« Reply #4361 on: October 01, 2016, 10:33:59 am »

Well, you stated
Quote
Unless you look at very wide-spectrum antibiotics a G- bacteria will simply not be susceptible to G+ bacteria's antibiotics, and vice-versa
Which seems to imply that  you have to look for unusual drugs in order to achieve this. I was merely pointing out that it is not that infrequent.
Fair enough, you have a point, I could have phrased that better, it is misleading.
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Re: SCIENCE, Gravitational waves, and the whole LIGO OST!
« Reply #4362 on: October 01, 2016, 12:48:41 pm »

I didn't actually know there was a resistance in the wild, how do we know that's the case?
I'm wondering why you should think it doesn't happen...
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Sergarr

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Re: SCIENCE, Gravitational waves, and the whole LIGO OST!
« Reply #4363 on: October 03, 2016, 06:44:25 am »

80% of data in Chinese clinical trials have been fabricated

Also, some people on forums are saying that the problem is even bigger, and can potentially affect ALL universities with Chinese Exchange programs, partnerships, or "visiting Scholars", due to them outsourcing "all Mass experiments, assays, and reproduction studies" to China because, apparently, the Chinese data is "Lots more data produced at a lower price, so it's far more efficient to do the mass studies that way".

This can go a long way to explain the current "crisis of reproducibility".
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BorkBorkGoesTheCode

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Re: SCIENCE, Gravitational waves, and the whole LIGO OST!
« Reply #4364 on: October 03, 2016, 07:05:16 am »

80% of data in Chinese clinical trials have been fabricated

Also, some people on forums are saying that the problem is even bigger, and can potentially affect ALL universities with Chinese Exchange programs, partnerships, or "visiting Scholars", due to them outsourcing "all Mass experiments, assays, and reproduction studies" to China because, apparently, the Chinese data is "Lots more data produced at a lower price, so it's far more efficient to do the mass studies that way".

This can go a long way to explain the current "crisis of reproducibility".
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