[HN Gopher] High time to tackle drug-resistant fungal infections
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High time to tackle drug-resistant fungal infections
Author : pmags
Score : 118 points
Date : 2025-04-16 13:22 UTC (3 days ago)
(HTM) web link (www.nature.com)
(TXT) w3m dump (www.nature.com)
| pmags wrote:
| From the editorial in Nature:
|
| _Around 3.8 million people die each year of infections caused by
| C. auris and other fungi. Annual deaths caused by fungal
| infections have nearly doubled in the past decade._
|
| _Pathogenic fungi pose unique challenges, and overcoming them
| will require innovative approaches to both science and policy.
| Yet, despite the growing global threat posed by drug-resistant
| fungi, such infections rarely loom large in discussions of
| antimicrobial resistance. Two World Health Organization (WHO)
| reports published this month (see go.nature.com /3rniybw) -- the
| organization's first analyses of tests and treatments for fungal
| infections -- highlight the result of that neglect._
| kinow wrote:
| Looks like this could affect how we grow crops, maybe pish for
| more different techniques to avoid pesticides, and also lead to
| new life habits.
|
| I hope WHO or some group of researchers somewhere will start
| studying how to tackle these fungi infections. Given the
| current situation of global conflicts, political situation, and
| economy around the world, if these infections become more
| widespread and resistent if could be devastating.
| Loughla wrote:
| Pesticides have nothing to do with this. Staple crops in the
| United States essentially do not use fungicides anymore. GM
| crops have negated that need.
|
| Edit: what did I say that was incorrect?
| pmags wrote:
| n.b. Down votes are not mine
|
| _Azoles (and other antifungals) are indeed still used in
| the US_ and there is documented azole resistance in
| important opportunistic fungal pathogens such as
| Aspergillus in the US:
|
| * Celia-Sanchez BN, Mangum B, Gomez Londono LF, Wang C,
| Shuman B, Brewer MT, Momany M. Pan-azole- and multi-
| fungicide-resistant Aspergillus fumigatus is widespread in
| the United States. Appl Environ Microbiol. 2024 Apr
| 17;90(4):e0178223. doi: 10.1128/aem.01782-23. Epub 2024 Apr
| 1. PMID: 38557086; PMCID: PMC11022549. --
| https://pmc.ncbi.nlm.nih.gov/articles/PMC11022549/
|
| Table 1 in this paper gives estimated azole use in various
| countries. US is lower than many European nations but still
| nowhere near zero.
|
| * Burks C, Darby A, Gomez Londono L, Momany M, Brewer MT.
| Azole-resistant Aspergillus fumigatus in the environment:
| Identifying key reservoirs and hotspots of antifungal
| resistance. PLoS Pathog. 2021 Jul 29;17(7):e1009711. doi:
| 10.1371/journal.ppat.1009711. PMID: 34324607; PMCID:
| PMC8321103. --
| https://pmc.ncbi.nlm.nih.gov/articles/PMC8321103/
| zdragnar wrote:
| The GP mentions "staple crops". In the US, azoles are
| used more on corn, wheat and soybean _seeds_ than they
| are the actual crops themselves. Rice, on the other hand,
| and others get direct applications to the crops.
|
| Presumably, applying it to the seeds going into storage
| is safer than applying in the open environment, but it's
| probably redundant since the Google claims azole use in
| the US is increasing.
| badmonster wrote:
| What would it take to create the "mRNA moment" for antifungal
| drugs--something that accelerates both funding and discovery at
| scale? Are there promising platforms (e.g. AI drug discovery,
| CRISPR screening, biofoundries) that could shift the economics of
| developing treatments for rare but rising fungal threats?
| mplewis9z wrote:
| I'm an outsider to that field, but I don't see a reason why
| mRNA can't be the "mRNA moment" - fungal vaccines are possible,
| and if you can find the right target protein you can make an
| mRNA vaccine against a particular infection.
|
| I think it's just a matter of priorities and funding, which
| fungal infections as a whole don't get enough of in general.
| jasfi wrote:
| Surgery is a real threat to get a potentially deadly fungal
| infection internally. Where are the options for treatment?
| Out_of_Characte wrote:
| Practically, there's no way to stop anti-microbial resistance.
| We've only been capable of using said drugs for an x number of
| years because of the relatively long time it takes for these
| resistant spores to become dominant in most soil around the
| planet. The problem isn't really the development of resistance
| itself but our way of farming is the perfect petri-dish for
| fungal and bacterial evoluton. E.G. large monocrop fields with
| single-use anti-fungal spray and rinse.
| kubb wrote:
| Found the ,,it can't be done" guy.
| worthless-trash wrote:
| At least its now out in the open.
| bravetraveler wrote:
| Found the German, can vs. should matters.
|
| Save this criticism for the people who aren't nuanced, they
| left avenues. Mitigation, not eradication.
|
| Before you take this personally, I'm talking about the
| quotes. Not history.
|
| _edit:_ downvoters and I would also disagree RE: Sisyphus.
| The punishment is worth it, bro. /s
| kubb wrote:
| I upvoted you in lieu of an olive branch.
| bravetraveler wrote:
| Points all around, this is more in jest than text
| generally allows
| jakobnissen wrote:
| I don't think that's right.
|
| * There is limited evidence that farming use of antibiotics is
| what drives resistance in clinical cases. That is - we use
| enormous amounts of antibiotics in farming, but the resistance
| it creates doesn't really seem to move into the hospitals.
|
| * There is no reason to believe we've hit a wall and can't
| invent more antibiotics in the future. Historically we haven't
| focused much on antibiotics because we already have a bunch,
| and because there is less money in developing those drugs
| compared to e.g. lifestyle drugs or chemotherapy.
|
| * We can still adopt better policies in the future to fight
| against resistance. For example, some countries crazily
| overprescribe antibiotics, or prescribe broad spectrum ones. We
| can also still amp up hygiene in hospitals - literally paying
| more people to scrub and boil and sterilize stuff will work.
|
| * There are still some antimicrobial treatment techniques we
| haven't put a lot of resources in. Like, bacteriophage
| treatments, or cycling antibiotics.
| _heimdall wrote:
| > There is no reason to believe we've hit a wall and can't
| invent more antibiotics in the future
|
| That just kicks the can down the road though. Assuming that
| the use of any antibiotic will eventually lead to a
| predominance of resistance, we would have to continue to
| invent new, effective antibiotics indefinitely.
|
| > For example, some countries crazily overprescribe
| antibiotics, or prescribe broad spectrum ones
|
| I don't think its as simple as over prescription being the
| problem. My grandmother is pretty I'll these days, she
| suffers from dementia, is sick frequently, and generally just
| very warn down. She had a respiratory infection this week and
| while at the doctor they also found that she has a UTI. The
| prescribed her two different, non-broad spectrum antibiotics.
|
| I don't think anyone would consider that over prescribing,
| and she likely would have a very bad outcome without it, but
| it also seems totally reasonable that her scenario could
| still lead to antibiotic resistance. Her immune system just
| doesn't work well anymore, the antibiotics will take out most
| of the infection and her symptoms will likely go away but I
| wouldn't expect her body to do the job of cleaning up the
| rest of the infection, leaving the more resistant strains
| around in her system.
| sarchertech wrote:
| We don't have to keep creating new antibiotics
| indefinitely. There's always some cost to resistance. Once
| a drug is no longer present in an environment, non-
| resistant strains tend to outcompete resistant ones. That
| is if you just stop using an antibiotic, bacteria will tend
| to lose resistance to it.
|
| Theoretically once you have enough antibiotics that we can
| retire drugs with heavy resistance and keep cycling them,
| you won't need to keep creating new antibiotics.
| _heimdall wrote:
| There's a lot baked into that theory (well, hypothesis)
| though. We haven't gone through a cycle like that yet
| that I'm aware of, moving back to an old antibiotic
| because the newer one is no longer effective.
|
| Looking just at the evolution of it, there would need to
| be pressure to actively select against the learned
| resistance. Maybe it would be lost eventually, but we
| couldn't rely on that unless something pushed the
| bacteria away from it rather learning to resist the new
| antibiotic in addition to the old one.
| sarchertech wrote:
| This has been well researched. Most antibiotic resistance
| has a fitness cost. Which means the resistance is being
| actively selected against.
|
| This isn't always the case. There are some adaptations
| that don't have an observable fitness cost, but the
| majority do. That is, in a lab when you remove the
| antibiotic, we observed that the number of resistant
| bacteria drops over time.
|
| We have also observed this in the real world. When we
| reduce usage of a specific antibiotic. The percentage of
| resistant bacteria in the wild drops.
|
| The question is how long you'd have to retire an
| antibiotic and how many different antibiotics you'd need
| for this strategy to be viable.
| biomcgary wrote:
| Everything that reproduces is in an evolutionary arms race
| (https://en.wikipedia.org/wiki/Evolutionary_arms_race), so
| the "kicking the can" objection doesn't really make sense
| in this context.
|
| There is no alternative to inventing new weapons
| continuously. We are simply used to winning without much
| effort since Fleming found penicillin, a naturally
| occurring fungal compound. Previous successes have limited
| the economics of continuing to develop new solutions, which
| is contributes to the uptick in resistance.
|
| This doesn't mean we shouldn't be judicious in the
| tradeoffs that we choose and try to avoid a purely chemical
| solution to the arms race. For example, as robotics get
| better, we should move away from mono-cropping toward
| combinations of plants that naturally ward off pests. There
| are better ways to stay ahead than blunt tools.
| Out_of_Characte wrote:
| >There is limited evidence that farming use of antibiotics is
| what drives resistance in clinical cases.
|
| This is a classic example of asymptotic behaviour analysis.
|
| >That is - we use enormous amounts of antibiotics in farming
|
| You're entirely correct, the data fits an almost exponential
| curve, the only limiting factor so far has been soil health
| and costs. the amount of biocides we have to use to keep our
| productivity will be impossible to match and therefore, even
| with 0 transference of resistance to human antibiotics,
| you're gonna see more transference to humans because of
| farming-biocide resistance. ofcourse, most of this will
| result in lower crop yield instead of actually selling bad
| product, this can be slowed down with essentially the same
| policies and techniques as hospitals employ. But the core
| problem is the exact same, the extremely quick and deadly
| takeover of a single strain resistent against our current quo
| pro due to overuse of a single line of defence.
| pmags wrote:
| I agree that there is still a lot we can do to combat fungal
| disease.
|
| However, your points 1, 2, and 4 unfortunately don't apply
| well to anti-fungals.
|
| * "There is limited evidence that farming use of [anti-
| fungals] is what drives resistance in clinical cases."
|
| Certainly not the case with respect to azoles:
|
| -- Rhodes J, et al. Population genomics confirms acquisition
| of drug-resistant Aspergillus fumigatus infection by humans
| from the environment. Nat Microbiol. 2022 May;7(5):663-674.
| doi: 10.1038/s41564-022-01091-2. Epub 2022 Apr 25. Erratum
| in: Nat Microbiol. 2022 Nov;7(11):1944. doi:
| 10.1038/s41564-022-01160-6. PMID: 35469019; PMCID:
| PMC9064804. https://pubmed.ncbi.nlm.nih.gov/35469019/
|
| -- Celia-Sanchez BN, Mangum B, Gomez Londono LF, Wang C,
| Shuman B, Brewer MT, Momany M. Pan-azole- and multi-
| fungicide-resistant Aspergillus fumigatus is widespread in
| the United States. Appl Environ Microbiol. 2024 Apr
| 17;90(4):e0178223. doi: 10.1128/aem.01782-23. Epub 2024 Apr
| 1. PMID: 38557086; PMCID: PMC11022549.
|
| -- Impact of the use of azole fungicides, other than as human
| medicines, on the development of azole-resistant Aspergillus
| spp. https://www.efsa.europa.eu/en/efsajournal/pub/9200
|
| "* There is no reason to believe we've hit a wall and can't
| invent more antibiotics in the future. "
|
| -- There are very few anti-fungals, because fungi, being
| eukaryotes, have cell biology so close to ours. The "big
| three" are 1) azoles (lots of resistance; see above); 2)
| echinocandins; and 3) amphotericin B (highly toxic to the
| host)
|
| -- One bright spot is a new antifungal published a few weeks
| ago in Nature, called Mandimycin:
| https://www.nature.com/articles/d41586-025-00801-0
|
| * "There are still some antimicrobial treatment techniques we
| haven't put a lot of resources in. Like, bacteriophage
| treatments, or cycling antibiotics."
|
| -- Bacteriophage don't work on fungi. Some degree of cycling
| and combination anti-fungal treatment are already in use.
| nabla9 wrote:
| //Thermotolerance Adaptation// The main reason why fungal
| infections typically kill only elderly and sick humans (mammals)
| is body temperature. Most fungi cannot survive at human body
| temperature (~37degC). Rising global temperatures are driving
| fungi to adapt by becoming more thermotolerant, enabling them to
| survive and replicate at human body temperatures.
|
| Effects of climate change on fungal infections
| https://journals.plos.org/plospathogens/article?id=10.1371%2...
|
| Zoonotic Risk from other mammals to humans will increase
| similarly. Pigs, cows or poultry might become spread the
| adaptions and then spread them to humans.
| dev_l1x_be wrote:
| The last of us are going to know how dangerous this is
| romaaeterna wrote:
| "Rising global temperatures are driving fungi to adapt by
| becoming more thermotolerant..."
|
| Your link only mentions Candida auris. I do not find it
| compelling to blame this on recent global warming for two
| reasons: 1) Regional and seasonal temperature variation is much
| greater than global variation and therefore the first place to
| look for temperature-specific adaptation, 2) The presence of an
| adaptation to the human body temperature in a human pathogen is
| not exactly remarkable or new.
|
| The thing about Candida auris is not that it is heat-resistant,
| but that it is drug resistant. IMO, it's worth looking at the
| evidence that the appearance of Candida auris is related to the
| use of agricultural antifungals in East Asian agricultural
| production.
| aziaziazi wrote:
| > appearance of Candida auris is related to the use of
| agricultural antifungals in East Asian agricultural
| production
|
| Can you elaborate on share documents on this? I'm wondering
| why east asia is different in anti fungal usage.
| romaaeterna wrote:
| "Can you elaborate on share documents on this?"
|
| https://archive.is/uTAaW
|
| "I'm wondering why east asia is different in anti fungal
| usage."
|
| It is a logical error to assume that it has to be
| substantially different. East Asia is simply the region
| that Candida auris originates from (ie., evolved in). It
| was first noticed in Tokyo and South Korea, and eventually
| India a few years later.
|
| EDIT:
|
| Actually, looks like there's some evidence that multiple
| evolutionarily-separate unrelated strains attained drug
| resistance one after another. Presumably the same
| antifungal agricultural product would have been in
| widespread use if this is the cause. If you look at the
| PLOS article linked in the NYT article in my link, they
| give an example of this for Aspergillus fumigatus strains.
|
| [1] https://journals.plos.org/plospathogens/article?id=10.1
| 371/j...
| pmags wrote:
| I too think that we don't yet have convincing evidence that
| recent changes in global temperature have driven thermal
| tolerance. However, there are some interesting aspect of C.
| auris that are worth pointing out:
|
| * C. auris does have unusual thermotolerance -- it grows up
| to 42C which is unusual compared to other Candida species.
|
| * C. auris does not appear to be a typical commensal of
| mammals, or other high body temp animals, and hence it's
| thermal tolerance is likely not due to selection for this
| aspect of the host niche
|
| Some more info on C. auris and hypotheses about origins here:
|
| * Sharma C, Kadosh D. Perspective on the origin, resistance,
| and spread of the emerging human fungal pathogen Candida
| auris. PLoS Pathog. 2023 Mar 23;19(3):e1011190. doi:
| 10.1371/journal.ppat.1011190. PMID: 36952448; PMCID:
| PMC10035752.
|
| But I agree
| chasil wrote:
| There are at least some cases where fungi can cause illness in
| otherwise healthy humans.
|
| The one that comes to mind is ergot, by ingestion of a chemical
| byproduct:
|
| https://en.m.wikipedia.org/wiki/Ergot
|
| A number of poisonous substances in mushrooms are reviewed in
| this wiki:
|
| https://en.m.wikipedia.org/wiki/Mushroom_poisoning
|
| I also checked "black mold," but it appears that link is not
| firmly established:
|
| https://en.m.wikipedia.org/wiki/Stachybotrys_chartarum
|
| Fungal pneumonia is well-known, but apparently not prevalent
| beyond the immunocompromised:
|
| https://en.m.wikipedia.org/wiki/Fungal_pneumonia
| metalman wrote:
| ummmm, hmmmmmmm, It's high time we realised that we are the
| largest single niche, and animal biomass, that possibly, has ever
| existed, and it is a law of biology, that each niche will be
| filled. This means that any peicemeal approach is going to lagg,
| and uncontrollable epidemics become more and more likely.
| Confounding factors are that our diets and lifestyles are
| converging into a more homegenous whole, and all in all we live
| longer, but are less fit ,while dependent on our haphazard use of
| "medicine" to provide cheap health care. My personal experience
| is that I now notice a lot more fungal smell in otherwise good
| looking food, and have stopped buying certain foods, not that I
| worryed about catching anything, but that it tastes bad, and is
| alarming only because it is a "stealth" fungus, often showing as
| just a tiny bit of black stuff, rather than an obvious fuzzy
| mess.
| mbil wrote:
| Humans aren't the largest biomass
| mrob wrote:
| Relevant paper: The biomass distribution on Earth
|
| https://www.pnas.org/doi/10.1073/pnas.1711842115
|
| I saw a good 3D visualization of this data using a customized
| version of Minecraft:
|
| https://www.youtube.com/watch?v=hXDZ2LTTKUE&t=505s
| maxerickson wrote:
| Yeah, that sounded wrong to me. We punch pretty high for a
| single species though:
|
| https://www.weforum.org/stories/2021/08/total-biomass-
| weight...
| chasil wrote:
| "By weight, human beings are insignificant."
|
| https://www.vox.com/science-and-health/2018/5/29/17386112/al...
|
| (Sorry you're getting down voted.)
| LinuxBender wrote:
| A few decades from now people will discover that drugs are not
| the right way to kill fungal infections.
| alganet wrote:
| Only fungal? What about funguy?
|
| What about letting a more innofensive variant spread? You know,
| not cleaning stuff just because it is slightly moldy (doesn't
| mean eating it!).
|
| It would be hilarious if cleaning is actually what selects the
| strongest bacteria and funghi to thrive. I mean tragic, not
| hilarious.
|
| But I'm no biologist. I have only mediocre high school
| understanding of such things.
| TZubiri wrote:
| What precisely is the suggested mechanism by which agricultural
| anfifungals affect human pathogens?
|
| Is it just that they select resistant fungi and we eat that?
|
| Or is it that we eat leftover azoles and thus build up immunity?
| asah wrote:
| #proudinvestor (very early angel) in Amplyx pharmaceuticals
| (fosmanogepix) from many years ago.
|
| fosmanogepix has proven anti-fungal activity in 4 of the 5 target
| classes and is in stage III trials.
|
| https://pmc.ncbi.nlm.nih.gov/articles/PMC11131969/
|
| https://www.google.com/search?q=amplyx+pharmaceuticals
|
| https://www.google.com/search?q=Fosmanogepix
| Retr0id wrote:
| > Between 30% and 60% of the people it infects will die.
|
| I assume there's an implicit "within x amount of time" here?
| ellen364 wrote:
| In the study I'm aware of, 18 patients became infected in
| hospital and there was a 28% death rate within 30 days [0]
|
| [0]
| https://www.journalofinfection.com/article/S0163-4453(16)301...
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