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Antibiotic resistance: what can we do about it?

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Nitish
Nitish Oct 26, 2020
Some microbes possess genes that help them neutralize different drugs or biocides. With the increasing use of antibiotics, microbes have been forced by humans to develop resistance against our most reliable saviors - antibiotics.

Until now, we have been lucky to triumph over pandemics. With increasing globalization, humanity has become interconnected more than ever before. This makes us an easy target for novel pathogens or those that manage to evolve resistance to our drugs.

What can we do about the growing problem of antibiotic resistance?

[1]Allen, H., Donato, J., Wang, H. et al. Call of the wild: antibiotic resistance genes in natural environments. Nat Rev Microbiol 8, 251–259 (2010). https://doi.org/10.1038/nrmicro2312

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Find new ways to destroy pathogenic bacteria - namely CRISPR.

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Jamila
Jamila Oct 26, 2020
Antibiotic resistance is a considerable problem. Right now, we can quickly treat infections, but this might change in the future if the current antibiotics stop working. Therefore, we desperately need to find novel antibiotics to eradicate pathogenic bacteria.

A startup company based in Denmark has started developing a method that might overcome antibiotic resistance. SNIPR BIOME plans to target specific bacterial strains or species with CRISPR technology (CRISPR is a biological tool that can edit genetic information). The company plans to use a CRISPR-Guided Vector, which contains the lab-made guide RNA. The CRISPR-Guide Vector will be paired up with the bacteria's own Cas proteins to initiate cell death in specific pathogenic bacteria.

Standard antibiotics destroy commensal bacteria as well as pathogenic bacteria. This isn't great because commensals have an essential role in the human body. Using CRISPR tech to target specific bacteria would be more beneficial as it would leave commensal bacteria intact. So, if the CRISPR technology works, it could become a next-generation antibiotic.

Apart from that, being able to regulate the human microbiome could have enormous applications for other health conditions too.

[1]Chokshi, Aastha, et al. "Global contributors to antibiotic resistance." Journal of global infectious diseases 11.1 (2019): 36.

[2]Terns, Michael P., and Rebecca M. Terns. "CRISPR-based adaptive immune systems." Current opinion in microbiology 14.3 (2011): 321-327.

[3]Langdon, Amy, Nathan Crook, and Gautam Dantas. "The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation." Genome medicine 8.1 (2016): 39.

[4]Khan, Rabia, Fernanda Cristina Petersen, and Sudhanshu Shekhar. "Commensal bacteria: an emerging player in defense against respiratory pathogens." Frontiers in Immunology 10 (2019): 1203.

[5]Askarova, Sholpan, et al. "The Links Between the Gut Microbiome, Aging, Modern Lifestyle and Alzheimer's Disease." Frontiers in Cellular and Infection Microbiology 10 (2020): 104.

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Nitish
Nitish6 months ago
I think the idea to find novel antibiotics against the resistant pathogen is very much abstract and does not seem to be that much reliable. Because once a pathogen develops resistance against a particular drug it certainly develops for others in a quicker way For eg. we have multi drug-resistant Staph aureus etc. CRISPR-Cas system is a promising tool but it has its own disadwantages and public prespectives and perceptions. We exactly dont know when we will be able to use this tool in public health. Therefore, for now, we dont have any method and technique on the ground to fighjt this virtual pandemic.
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Manel Lladó Santaeularia
Manel Lladó Santaeularia3 months ago
Nitish Absolutely agree with you. Also, using CRISPR is not necessarily the panacea. First, you would need to target CRISPR to specific sequences, probably of the bacteria's DNA, and random mutations would be selected for, conferring bacteria resistance against that CRISPR treatment.

Also, the main problem as always is delivery: how do we make our gRNAs reach the specific bacteria we want to eliminate? SNIPR BIOME proposes using strain-specific CRISPR-Guided Vectors but I would need to find more information on how they work. Still, while this could work for the gut microbiota, it could be way more complicated to deliver for other infections like respiratory or urinary infections.

Take antibiotics only when absolutely necessary

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Shubhankar Kulkarni
Shubhankar Kulkarni Oct 26, 2020
The usual infections (for example, some of the respiratory tract, ear, nose, throat, lungs, skin) do not need antibiotic therapy. Natural immune boosters, some physical therapies like steam, and rest are sufficient to get you through. Antibiotics are necessary if the infection is severe, if you have other comorbidities like diabetes or other conditions that have deteriorated your immune system, you have had immunosuppressants after surgery, or you are elderly. If taking antibiotics becomes habitual, you unintentionally train the microbes to grow stronger and develop resistance against the medication.

More responsible doctor's prescriptions

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Martina Pesce
Martina Pesce Oct 26, 2020
It's unluckily very common for doctors, especially the older ones , to prescribe antibiotics even when not strictly necessary.
I wish we could just wait for them to reach retirement, but given how much resistance to antibiotics has raised , something must be done in the meantime.

I believe it would be useful to create a very detailed and precise protocol on how and when to prescribe antibiotics. It should be worldwide recognized and imposed by law, so that doctors, afraid of being fined, would think twice before prescribing an antibiotic without even seeing the patient or without being sure of the diagnosis.
I'd say this should really be a reality for at least the cases of not severe respiratory inflammations, where an eventual missed diagnosis would not lead to serious consequences.


Also, better schooling (campaign, school) of the population on the topic would help.

[1]T. P. Lam and K. F. Lam, “What are the non-biomedical reasons which make family doctors over-prescribe antibiotics for upper respiratory tract infection in a mixed private/public Asian setting?,” J. Clin. Pharm. Ther., 2003.

[2]“Race against time to develop new antibiotics,” Bull. World Health Organ., 2011.

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Nitish
Nitish6 months ago
A philosophical solution though. The practicality of which is certainly not accountable.
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Shubhankar Kulkarni
Shubhankar Kulkarni6 months ago
Martina Pesce I agree that doctors should prescribe antibiotics responsibly. There exist standard protocols (might differ from country to country) for the administration of antibiotics. [1,2] However, the decision of prescription of the antibiotics lies with the physicians. I don't think there exists enforcement of these rules, at least for those pertaining to prescribing antibiotics. Complex procedures and surgeries might have rules enforced strictly. From the physician's point of view, the symptoms vary largely from patient to patient. A "one rule fits all" strategy does not work. I don't know how we can come up with a solution that respects both views.

References:
1. https://www.nice.org.uk/about/what-we-do/our-programmes/nice-guidance/antimicrobial-prescribing-guidelines
2. http://iamrsn.icmr.org.in/images/pdf/STG270217.pdf

Implementing "natural antibiotics" in our diet

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J
J. Oct 28, 2020
Although antibiotics are usually in a form of pills, they are mostly plant-derived. Pills with high doses of specific antibiotics are inevitable in critical infections, but if we implemented more natural sources of antibiotics in our everyday diet, we could develop certain background immunity and reduce the chance of infection. The most commonly mentioned plants that have an impressive antibiotic effect are:

  1. Garlic (inhibits the growth of Salmonella, Escherichia coli, MDR tuberculosis)
  2. Honey (helps wound healing by inhibition of bacterial growth)
  3. Ginger (fight of many bacteria)
  4. Echinacea (kill many different kinds of bacteria, including Streptococcus pyogenes; fights inflammation)
  5. Goldenseal (respiratory and intestinal problems; skin infections)
  6. Clove (water solution effective against many bacteria)
  7. Oregano (immuno booster, antioxidant, oregano oil has good antibacterial characteristics)
  8. Red pepper (inhibiting the bacteria growth)
  9. Cinnamon (effective in treating conditions caused by bacteria and viruses, even funghi)
  10. Turmeric (reducing the activity of the microbes; anti-inflammatory)
etc.


[1]https://www.medicalnewstoday.com/articles/321108#seven-best-natural-antibiotics

[2]https://www.medlife.com/blog/12-best-natural-antibiotics-infection/#4-red-pepper

Hospitals should strictly comply with the cleaning and safety procedures

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Shubhankar Kulkarni
Shubhankar Kulkarni Oct 26, 2020
Hospitals are one of the major sources of multi-resistant infections. If the beds, sheets, and surgical instruments are not cleaned as per the given norms, the infections might spread. Nonoptimal cleaning procedures make the pathogens stronger.
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Povilas S
Povilas S6 months ago
I've heard about a study which showed that only 1/3 of the doctors (as far as I remember) wash their hands before and after entering the hospital room (I think it was the operating room or maybe a room where they inspect patients, etc.). And it didn't change even after they installed cameras and put signs about this:D

Do not miss your antibiotic doses

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Shubhankar Kulkarni
Shubhankar Kulkarni Oct 26, 2020
If you are on antibiotic therapy, it is absolutely important that you take your required doses on time. Delaying, missing, or reducing the dosage can, too, lead to antibiotic resistance.
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Darko Savic
Darko Savic6 months ago
And finish the entire course as prescribed. Often that means continuing to take the antibiotics past the time where you feel well again. Any microbes that manage to survive are the ones most likely to evolve antibiotic resistance. So finish them off properly while you have the upper hand.

Try to prevent infections in the first place

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Jamila
Jamila Oct 26, 2020
If we can prevent the spread of infectious diseases, fewer people would get ill, and then the antibiotics would be used less. Hopefully, this would decrease the possibility of antibiotic resistance occurring. We can try to prevent infections by regularly washing our hands, having our vaccinations, and limiting contact with other people when we are ill.

Antibiotics resistance is not necessarily being spread by taking these drugs directly

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Nitish
Nitish Oct 28, 2020
This is true that in recent past mostly after WWII, we have started consuming antibiotics for every minute ailments, which has substantially contributed to the development of resistance among most of the pathogens. But there are other factors also like poultry, drinking water, vegies etc. etc. Antibiotics are used in many cases. This is scary, but we are being surrounded by these drugs and the pathogens are growing resistance against them.

Blocking the bacterial "evolvability factors"

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Shubhankar Kulkarni
Shubhankar Kulkarni Nov 02, 2020
Bacterial species produce certain proteins called "evolvability factors". For example, the DNA translocase protein Mfd increases mutation rates and speeds up resistance in diverse species toward every antibiotic that was tested. Bacterial cells missing Mfd are not more sensitive to DNA-damaging agents. However, cells with too much of Mfd are more prone to DNA damage. Therefore, one of the strategies to reduce the chances of antibiotic resistance can be to block these evolvability factors using anti-evolution drugs.

[1]https://www.sciencedaily.com/releases/2018/11/181116164514.htm

Antimicrobial peptides as potent weaponry against pathogens

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Nitish
Nitish Feb 02, 2021
Bioactive peptides are the host organisms' defence mechanism against pathogens. They are reported in various organisms from prokaryotes to humans, and are known to possess the anti-microbial ability. They work differentially either directly kill pathogens or modulates the hosts' immune system against invading pathogens . However, their ability mechanisms are still not clear at the molecular level, but there has been an urgency to explore their capability to kill drug-resistant pathogens. As we are almost in the post-antibiotic era, it is necessarily important to discover the alternatives for drugs but also effective molecules against already resistant microbes should be explored.

[1]Mahlapuu, M., Håkansson, J., Ringstad, L. and Björn, C., 2016. Antimicrobial peptides: an emerging category of therapeutic agents. Frontiers in cellular and infection microbiology, 6, p.194.

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Shubhankar Kulkarni
Shubhankar Kulkarni3 months ago
Hi Nitish! Are you suggesting using these antimicrobial peptides as drugs to kill pathogens? If yes, how will that overcome the problem of drug resistance? Also, what if the pathogens develop resistance against the antimicrobial peptides?

I like the idea of modulating the host's immune system instead of targetting the pathogens. Correct me if I am wrong but won't they act like vaccines?
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Nitish
Nitish3 months ago
Shubhankar Kulkarni Yes sir, I am suggesting the use of antimicrobial peptides as potential drugs against resistant microbes. Actually, there are already so many peptides reported from various sources including human milk which shows tremendous antimicrobial activities. However, they have never been employed against resistant microbes. Which will be a good alternative, I guess. If we could kill such bugs with peptides, we will need not to search for new drugs and dissemination of resistance among microbes can be handled. Yes, I completely agree with you on peptide resistance, microbes can develop different strategies to fight with these peptides, and one of such is proteases. However, there are so many antimicrobial peptides in counterbalance having proteases stability, mechanisms of which can be explored in antimicrobial peptides against resistant microbes.
All the peptides don't act as vaccines, and it certainly depends upon the source of these peptides. For example, the peptides from human sources or some prokaryotes simply act as the first defence line. They work as first-hand weaponry against invading microbes. However, peptides from microbial sources can generate an immune response in humans as vaccines, which need to be explored further. Till date, only synthetic peptides are being used as vaccines, which mimic the structural components of natural microbes.
Anti-microbial peptides are the promising alternatives to traditional antibiotic drugs; however, there are some limitations such as stability, short half-life, toxic side effects of these biomolecules needs to be explored further in details.

Strictly avoid using expired antibiotics

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Shubhankar Kulkarni
Shubhankar Kulkarni Oct 26, 2020
Antibiotics with a reduced efficacy can make the pathogen resistant to it. Checking the expiry on the antibiotics before use is important.

Proper disposal of expired antibiotics

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Shubhankar Kulkarni
Shubhankar Kulkarni Oct 26, 2020
They may help develop resistance in the pathogens in the environment if they are disposed of without proper deactivation.

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