11 ms·

With chemical tweaks, an old antibiotic is now more potent and resistant

85 points by kposehn 9y ago

mrfusion 9y ago
Does it only work on gram positive? I thought most bad bacteria were gram negative?
- hprotagonist 9y ago
  gram positive only, but it's still a great idea.
  - ericcholis 9y ago
    For reference; MRSA, which seems to be typically associated with "superbugs", is gram positive.
    - Declanomous 9y ago
      Just to clarify, in case anyone isn't aware, MRSA refers to a any number of bacteria in the genus Staphylocaccus which is resistant to methicillin. (Methicillin-resistant Staphylococcus aureus) It is generally also resistant to another of other common antibiotics such as amoxicillin, penicillin and oxacillin. The big deal about MRSA is that bacteria can transfer parts of their genome to other bacteria, so if one strain of staph becomes resistant to antibiotics, it can transfer that trait to other strains of staph. The good news is that all Staphylocaccus bacteria are gram-positive, so you not only gain the ability to treat MRSA, you gain the ability to treat bacteria that might become MRSA.
- giarc 9y ago
  Somewhat. A few bad Gram positives are coagulase negative Staphylococcus, MRSA, Streptococcus pyogenes/pneumoniae/virdans/mitis etc.
Ductapemaster 9y ago
Fascinating development, but Ars's writing is just plain awful. Is there a more academic article on the subject?
- gilleain 9y ago
  There is some more detail here : https://biology.stackexchange.com/questions/60251/how-do-the-three-mechanisms-of-the-1000x-improved-new-vancomycin-work-together https://biology.stackexchange.com/questions/60251/how-do-the...
- scarhill 9y ago
  Not an academic article, but Derek Lowe at In the Pipeline has a more technical write-up: http://blogs.sciencemag.org/pipeline/archives/2017/05/30/antibiotic-progress-and-not-a-moment-too-soon http://blogs.sciencemag.org/pipeline/archives/2017/05/30/ant...
  - Ductapemaster 9y ago
    Love Derek Lowe! Thank you!
- Timshel 9y ago
  The original paper is on sci-hub and is ten pages long.
btilly 9y ago
I think I get the underlying idea, and it is clever. A traditional antibiotic does one nasty thing to the bacteria. So if bacteria find a single point mutation that helps, there is an evolutionary advantage. This allows resistance to evolve fairly easily once the mutation comes along. But this is doing several nasty things to bacteria at once, in parallel. So a point mutation that helps with any one attack confers only a minor selection benefit because the others still kill the bacteria. Ideally it would want to evolve a combination of resistances to different attacks in parallel, but that isn't how evolution works. Resistance can still evolve, but it will be much slower. Improved resistance to whatever is currently the deadliest attack does have a selection benefit, and will spread. But it will be a smaller benefit, and the evolutionary path to full resistance is much longer. So the process is slowed.
- evilduck 9y ago
  I'm a complete layperson to the topic, but wouldn't having more attack avenues that must be evolved against also result in more resources dedicated to survival and eventually compromise the dangerous impact bacteria could have in the first place? i.e. if it's spending energy building anti-anti-bacterial mechanisms, it's not spending as much energy replicating or producing a toxin or whatever.
  - rcar 9y ago
    That's not really how antibiotic resistance develops: it happens at a population-level rather than an individual bacterium level. If, for example, you've got an antibiotic that messes with normal cell wall formation in a particular species, but some in the population randomly have some mutation that still allows the cell wall to function normally, those bacteria will survive the antibiotic. If the infection isn't then controlled by other means, the resistant bacteria will make up a larger percentage of the infecting bacterial population in the next generation. That's why taking full courses of antibiotics is important so that your immune system can focus on the resistant bacteria that the antibiotic can't touch.
  - Declanomous 9y ago
    You have part of the idea right. However you have to consider that evolutionary pressure works with regards to competition for resources. So yes a drug-resistant bacteria might be outcompeted for limited resources in a normal environment by bacteria without that adaptation. However, if there is an antibiotic introduced into the environment, the drug-resistant bacteria will probably have proportionally more resources than the non-adapted bacteria did before the drug was introduced, due to a complete elimination of their competition. This is assuming that the adaptations bacteria have that enables them to be drug resistant harm their fitness in a drug-free environment in the first place. It is entirely possible that the drug was targeting a trait that actually required more resources to produce, but that wasn't selected against because it was basically vestigial. I think it's a pretty big misconception that the force of natural selection is directed towards absolute efficiency. I'd classify the process of natural selection as a 'good enough' mechanism.
ryanmarsh 9y ago
Vanc is often given to immunodeficient cancer patients. Hopefully this will allow more patients to finish their protocols with shorter/fewer delays due to infection.
ComputerGuru 9y ago
I get that it's supposed to be "resistant" to drug resistance and all, but nevertheless, it's probably a good idea if we keep this one out of the reach of livestock farmers.
- ianlevesque 9y ago
  Particularly given that even in their tests bacteria were still (very) slowly gaining resistance.
- pif 9y ago
  ... and if we only administer it in hospitals (or under medical control anyway): the right quantity for the right time, no more, no less!
- bluGill 9y ago
  livestock farmers have to get a vet to prescribe their antibiotics. Even a few years ago when they didn't they were not allowed to use antibiotics that were useful in humans. Antibiotic resistance is a real thing, but livestock farmers were not a major concern. Those farmers were consistent and controlled in their use (and couldn't sell anything with detectable levels of antibiotics in it). The real problem was humans who got an antibiotic take it a couple times, felt better and stopped, allowed the bacteria that had a little resistance to survive.
  - mikeash 9y ago
    According to this, medically important drugs can still be used for disease prevention in livestock, albeit with the approval of a veterinarian: https://www.fda.gov/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/ucm216939.htm#question6 https://www.fda.gov/AnimalVeterinary/GuidanceComplianceEnfor... This seems completely insane to me. I'm not concerned about antibiotics in my food, but rather frequent antibiotic use in animals resulting in resistant diseases which then make the jump to humans.
    - bluGill 9y ago
zrth 9y ago
First time i recall seeing a link to an article, supposedly about some positive news related to the state of antibiotics. Will we in the closer future start seeing masses of these articles? kind of like: s/new battery breakthrough/killer antibiotic/g
StreamBright 9y ago
Can't wait to see the first nanotechnology based antibiotic.
Mz 9y ago
Okay, cool. But when do we get genuinely clever and learn to support the body's own defenses instead?
Madmallard 9y ago
This is going to kill people Maybe less than would die from resistant infections initially- but i'm betting the genetic consequences from the side effects will probably kill more people in the long run and weaken the species overall

85 points by kposehn 9y ago

mrfusion 9y ago

Does it only work on gram positive? I thought most bad bacteria were gram negative?

hprotagonist 9y ago
gram positive only, but it's still a great idea.
- ericcholis 9y ago
  For reference; MRSA, which seems to be typically associated with "superbugs", is gram positive.
  - Declanomous 9y ago
    Just to clarify, in case anyone isn't aware, MRSA refers to a any number of bacteria in the genus Staphylocaccus which is resistant to methicillin. (Methicillin-resistant Staphylococcus aureus) It is generally also resistant to another of other common antibiotics such as amoxicillin, penicillin and oxacillin. The big deal about MRSA is that bacteria can transfer parts of their genome to other bacteria, so if one strain of staph becomes resistant to antibiotics, it can transfer that trait to other strains of staph. The good news is that all Staphylocaccus bacteria are gram-positive, so you not only gain the ability to treat MRSA, you gain the ability to treat bacteria that might become MRSA.
giarc 9y ago
Somewhat. A few bad Gram positives are coagulase negative Staphylococcus, MRSA, Streptococcus pyogenes/pneumoniae/virdans/mitis etc.

Ductapemaster 9y ago

Fascinating development, but Ars's writing is just plain awful. Is there a more academic article on the subject?

gilleain 9y ago
There is some more detail here : https://biology.stackexchange.com/questions/60251/how-do-the-three-mechanisms-of-the-1000x-improved-new-vancomycin-work-together https://biology.stackexchange.com/questions/60251/how-do-the...
scarhill 9y ago
Not an academic article, but Derek Lowe at In the Pipeline has a more technical write-up: http://blogs.sciencemag.org/pipeline/archives/2017/05/30/antibiotic-progress-and-not-a-moment-too-soon http://blogs.sciencemag.org/pipeline/archives/2017/05/30/ant...
- Ductapemaster 9y ago
  Love Derek Lowe! Thank you!
Timshel 9y ago
The original paper is on sci-hub and is ten pages long.

btilly 9y ago

I think I get the underlying idea, and it is clever. A traditional antibiotic does one nasty thing to the bacteria. So if bacteria find a single point mutation that helps, there is an evolutionary advantage. This allows resistance to evolve fairly easily once the mutation comes along. But this is doing several nasty things to bacteria at once, in parallel. So a point mutation that helps with any one attack confers only a minor selection benefit because the others still kill the bacteria. Ideally it would want to evolve a combination of resistances to different attacks in parallel, but that isn't how evolution works. Resistance can still evolve, but it will be much slower. Improved resistance to whatever is currently the deadliest attack does have a selection benefit, and will spread. But it will be a smaller benefit, and the evolutionary path to full resistance is much longer. So the process is slowed.

evilduck 9y ago
I'm a complete layperson to the topic, but wouldn't having more attack avenues that must be evolved against also result in more resources dedicated to survival and eventually compromise the dangerous impact bacteria could have in the first place? i.e. if it's spending energy building anti-anti-bacterial mechanisms, it's not spending as much energy replicating or producing a toxin or whatever.
- rcar 9y ago
  That's not really how antibiotic resistance develops: it happens at a population-level rather than an individual bacterium level. If, for example, you've got an antibiotic that messes with normal cell wall formation in a particular species, but some in the population randomly have some mutation that still allows the cell wall to function normally, those bacteria will survive the antibiotic. If the infection isn't then controlled by other means, the resistant bacteria will make up a larger percentage of the infecting bacterial population in the next generation. That's why taking full courses of antibiotics is important so that your immune system can focus on the resistant bacteria that the antibiotic can't touch.
- Declanomous 9y ago
  You have part of the idea right. However you have to consider that evolutionary pressure works with regards to competition for resources. So yes a drug-resistant bacteria might be outcompeted for limited resources in a normal environment by bacteria without that adaptation. However, if there is an antibiotic introduced into the environment, the drug-resistant bacteria will probably have proportionally more resources than the non-adapted bacteria did before the drug was introduced, due to a complete elimination of their competition. This is assuming that the adaptations bacteria have that enables them to be drug resistant harm their fitness in a drug-free environment in the first place. It is entirely possible that the drug was targeting a trait that actually required more resources to produce, but that wasn't selected against because it was basically vestigial. I think it's a pretty big misconception that the force of natural selection is directed towards absolute efficiency. I'd classify the process of natural selection as a 'good enough' mechanism.

ryanmarsh 9y ago

Vanc is often given to immunodeficient cancer patients. Hopefully this will allow more patients to finish their protocols with shorter/fewer delays due to infection.

ComputerGuru 9y ago

I get that it's supposed to be "resistant" to drug resistance and all, but nevertheless, it's probably a good idea if we keep this one out of the reach of livestock farmers.

ianlevesque 9y ago
Particularly given that even in their tests bacteria were still (very) slowly gaining resistance.
pif 9y ago
... and if we only administer it in hospitals (or under medical control anyway): the right quantity for the right time, no more, no less!
bluGill 9y ago
livestock farmers have to get a vet to prescribe their antibiotics. Even a few years ago when they didn't they were not allowed to use antibiotics that were useful in humans. Antibiotic resistance is a real thing, but livestock farmers were not a major concern. Those farmers were consistent and controlled in their use (and couldn't sell anything with detectable levels of antibiotics in it). The real problem was humans who got an antibiotic take it a couple times, felt better and stopped, allowed the bacteria that had a little resistance to survive.
- mikeash 9y ago
  According to this, medically important drugs can still be used for disease prevention in livestock, albeit with the approval of a veterinarian: https://www.fda.gov/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/ucm216939.htm#question6 https://www.fda.gov/AnimalVeterinary/GuidanceComplianceEnfor... This seems completely insane to me. I'm not concerned about antibiotics in my food, but rather frequent antibiotic use in animals resulting in resistant diseases which then make the jump to humans.
  - bluGill 9y ago

zrth 9y ago

First time i recall seeing a link to an article, supposedly about some positive news related to the state of antibiotics. Will we in the closer future start seeing masses of these articles? kind of like: s/new battery breakthrough/killer antibiotic/g

StreamBright 9y ago

Can't wait to see the first nanotechnology based antibiotic.

Mz 9y ago

Okay, cool. But when do we get genuinely clever and learn to support the body's own defenses instead?

Madmallard 9y ago

This is going to kill people Maybe less than would die from resistant infections initially- but i'm betting the genetic consequences from the side effects will probably kill more people in the long run and weaken the species overall