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  • Writer's pictureJoan Rothchild Hardin

WEIRD SCIENCE: Antimicrobial Resistant Infections on the Frontiers of Drug Discovery & Development


Parts of this article are going to seem like science fiction but I assure you it's all true!




ANTIMICROBIAL RESISTANCE


The golden age of antibiotics began in 1928 with the discovery of penicillin and peaked in the mid-1950s. In the decades since then, antibiotics have been misused (given for viral infections), over prescribed and widely given to factory farmed animals to keep them alive in overcrowded, unsanitary conditions. At the same time, the discovery and development of new antibiotics gradually declined. All this led to drug resistance in many human pathogens and the current antimicrobial resistance crisis.


Antimicrobial resistance is when "germs like bacteria and fungi develop the ability to defeat the drugs designed to kill them. That means the germs are not killed and continue to grow. Resistant infections can be difficult, and sometimes impossible, to treat.




"Antimicrobial resistance is an urgent global public health threat, killing at least 1.27 million people worldwide and associated with nearly 5 million deaths in 2019. In the U.S., more than 2.8 million antimicrobial-resistant infections occur each year. More than 35,000 people die as a result, according to CDC’s 2019 Antibiotic Resistance (AR) Threats Report.


"When Clostridioides difficile—a bacterium that is not typically resistant but can cause deadly diarrhea and is associated with antimicrobial use—is added to these, the U.S. toll of all the threats in the report exceeds 3 million infections and 48,000 deaths.


"Antimicrobial resistance has the potential to affect people at any stage of life, as well as the healthcare, veterinary, and agriculture industries. This makes it one of the world’s most urgent public health problems." (CDC, 2022)


Now here comes the weird science!



USING BACTERIA EATING AMOEBAS TO TREAT ANTIBIOTIC RESISTANT INFECTIONS


A week ago the March 2024 issue of a journal called DDN: Exploring Drug Discovery and Development turned up in my mail box chock full of interesting articles about research being done at the frontiers of science. The cover highlights a particularly interesting article called A Predatory Nature: Many species of amoebae naturally bust open biofilms to eat the bacteria inside. Now, scientists are mining these microbial predators for new ways to treat antibiotic resistant infections.


I'm fascinated by biofilms and antimicrobial resistance concerns me greatly so this article grabbed my attention.





Amoebas break open biofilms and eat the bacteria inside?!!


Sounds like a scary science fiction flick!



ABOUT BIOFILMS


Biofilms are assemblages of microbial cells that are "irreversibly associated ... with a surface and enclosed in a matrix of primarily polysaccharide material.


"An established biofilm structure comprises microbial cells..., has a defined architecture, and provides an optimal environment for the exchange of genetic material between cells.... Biofilms have great importance for public health because of their role in certain infectious diseases and importance in a variety of device-related infections. A greater understanding of biofilm processes should lead to novel, effective control strategies for biofilm control and a resulting improvement in patient management." (Donlan, 2002)


BIOFILMS




To read more about biofilms, the origin of life on our planet 3.8 billion years ago, see my 21 January 2024 article PROBLEMATIC BIOFILMS IN YOUR BODY - AND SOME THAT ARE PROTECTIVE.




BACK TO AMOEBAS THAT EAT ANTIBIOTIC RESISTANT BACTERIA LIVING INSIDE BIOFILMS


Turns out some amoebas' favorite food is bacteria! And some of these kinds of amoebas are able to burst open biofilms containing antimicrobial-resistant bacteria. This ability offers a potential new tool for treating antibiotic-resistant infections - just as pharmaceutical antibiotics are losing their effectiveness.




An example of an amoeba that can break down a biofilm containing gut bacteria to feed on and destroy the bacteria inside is shown in this image:


Entamoeba histolytica, a Parasitic Amoeba (green) Consuming a Bacillus subtilis Biofilm (red)




Amoebas are bacteria's natural predators - what some species of amoebas like to eat.


"Bacteria, in general, don't really exist as single cells for very long in the environment because it's stressful. There're things hunting them, trying to kill them, so one of the ways that they protect themselves is by forming biofilms.... Biofilms help bacteria survive temperature and desiccation stresses as well as resist killing by the immune system and antibiotics." (Demarco, 2024)


Amoebas have the ability to disrupt the biofilms bacteria create to protect themselves from being destroyed. Researchers looking to use amoebas to treat antibiotic resistant infections must match the amoeba with the type of bacteria it feeds on. "We wanted to see if we could use amoebae to break open biofilms.... If they can get [bacterial cells] to leave that protection, they they can actually engulf them and eat them." (Demarco, 2024)


Entamoeba histolytica is a human parasitic amoeba responsible for the disease amoebiasis, a bowel illness spread through human feces. "The parasite enters the human body through contaminated food or water, and, when in the colon, feeds on gut microbiota bacteria, intestinal mucus, and finally epithelial cells. After degrading the epithelial cell, it reaches the blood stream and the parasite can cause liver or lung abscesses and even death (100,000 death every year worldwide." (Kolodkin-Gal, 2023)


In the image above, E. histolytica amoebas are being used therapeutically to break open the biofilm around gram-positive B. subtilis bacteria to get in and eat the bacteria. B. subtilis bacteria are actually probiotic bacteria (good guys in the gut microbiome) that have beneficial effects on the human intestinal microflora. They increase the count of beneficial bacteria such as lactic acid bacteria and decrease the harmful ones so are used in food products to prevent food borne diseases.


Even though B. subtilis are good bacteria commonly found in fermented foods, they and the protective endospores they grow to protect themselves have been well studied and are often used in research studies like the amoeba work described in the DDN article. After working with B. subtilis, the research team went on to demonstrate five different soil amoebas' ability to vanquish some antibiotic resistant and other dangerous bacterial strains:


  • Methicillin-resistant Staphylococcus aureus (MRSA), a common hospital acquired infection

  • Mycobacterium bovis, responsible for causing bovine tuberculosis, which can lead to zoonotic tuberculosis in humans

  • Escherichia coli (E. coli)

  • Salmonella enterica

  • Enterococcus faecalis


Brad Borlee, a microbiologist at Colorado State University and Principal Investigator for the amoeba research team, said, "I was just shocked at how rapidly they were able to destroy the biofilms of Staph aureus. It looked like Pac-Man chewing through the biofilm." (Demarco, 2024)


"For regulatory reasons, using (live) amoebae is a bit of a nightmare." So focusing on the compounds the amoebas produce is more more realistic for getting further research approved. "So far, they have identified compounds released by amoebae that work synergistically with antibiotics to lower the concentration of antibiotics needed to kill a particular bacterial species." (Demarco, 2024)



MORE EVIDENCE OF WHAT PREDATORY AMOEBAS CAN DO IN THE WAR AGAINST DANGEROUS BACTERIA



Amazing Amoebas - BEAUTIFUL & MIND BLOWING



Unicellular amoebas swarm across a Petri dish, devouring a "lawn" of bacteria as they go



Amoeba Warfare: Two strains of amoebas break through bacterial biofilms to devour the bacteria inside




HOW ABOUT PHAGES, VIRUSES THAT EAT BACTERIA - INCLUDING DEADLY ANTIBIOTIC-RESISTANT SUPERBUGS?


If thrillers are your thing, here's a true story that's a thriller from the frontier of medicine - about a race to cure a deadly superbug infection: The Perfect Predator: A Scientist's Race to Save Her Husband from a Deadly Superbug.





"Epidemiologist Steffanie Strathdee and her husband, psychologist Tom Patterson, were vacationing in Egypt when Tom came down with a stomach bug. What at first seemed like a case of food poisoning quickly turned critical, and by the time Tom had been transferred via emergency medevac to the world-class medical center at UC San Diego, where both he and Steffanie worked, blood work revealed why modern medicine was failing: Tom was fighting one of the most dangerous, antibiotic-resistant bacteria in the world.


"Frantic, Steffanie combed through research old and new and came across phage therapy: the idea that the right virus, aka "the perfect predator," can kill even the most lethal bacteria. Phage treatment had fallen out of favor almost 100 years ago, after antibiotic use went mainstream. Now, with time running out, Steffanie appealed to phage researchers all over the world for help. She found allies at the FDA, researchers from Texas A&M, and a clandestine Navy biomedical center -- and together they resurrected a forgotten cure.


"A nail-biting medical mystery, The Perfect Predator is a story of love and survival against all odds, and the (re)discovery of a powerful new weapon in the global superbug crisis." (Amazon, 2024)


A RIVETING, PULSE-POUNDING MEDICAL THRILLER THAT JUST HAPPENS TO BE TRUE. STRATHDEE IS EXPERT AT WEAVING SCIENCE INTO COMPULSIVELY READABLE PROSE







Viral bacteriophage therapy saved Tom Patterson's life and has also been used on other people in critical condition with lethal, antibiotic-resistant infections. To read more about the fascinating state of bacteriophage therapy, see Phage Therapy: Past, Present and Future by Dr Madeline Barron of the American society of Microbiology. (Barron, 2022)


Bacteriophages, phages for short, are simple viruses that selectively target bacteria and eat them. Phages are the most common biological entities on earth, found abundantly in the soil, water, deep inside the earth's crust, inside plants and animals, in the oceans and in human feces, saliva, sputum, blood and urine. Phages constantly devour bacteria wherever they can find them.


Viral Phages Attacking Bacteria



Here's a good video for those of you who want to know more about bacteriophages and phage therapy:


The Deadliest Being on Planet Earth – The Bacteriophage






AND THERE'S ALSO MANUKA HONEY: A POTENT NATURAL ANTIBIOTIC





"Of all the 300 types of honey in the world, manuka honey is the most unique and beneficial. It is produced in New Zealand and Australia, from European honey bees that pollinate the manuka bush (leptospermum scoparium).


Manuka Bush in New Zealand


Manuka honey is one of the richest antimicrobial sources in nature, effective for healing burns, wounds, sore throats, C. difficile and other digestive problems, Staph infections, eczema, acne, gingivitis, tooth decay, ulcers, MRSA and seasonal allergies.




"Of manuka honey’s many medicinal properties, its effectiveness as an antibacterial agent is the most astounding.

An article published in the European Journal of Clinical Microbiology and Infectious Diseases in 2009 demonstrated that medical grade manuka honey works better than all antibiotics against eight species of wound pathogens, including ones with acquired antibiotic resistance. Furthermore, resistance to the honey couldn’t be induced under conditions that rapidly induced resistance to antibiotics. (Blair et al, 2009)


The honey also remained effective even after multiple treatments. None of the superbugs killed by the honey was able to achieve immunity, which is the greatest concern regarding the antibiotics in current use." (Hardin, 2018)


Manuka Honey Is Effective Against the Superbug MRSA


To learn even more about the extraordinary medicinal properties of manuka honey, see my 1 July 2018 article MANUKA HONEY: DELICIOUS & THERAPEUTIC.




THE BOTTOM LINE


"Antimicrobial resistance (AMR) has made it so that, for a growing number of bacterial pathogens, the success rate of antibiotics is iffy, at best. More than 1.2 million people died as a direct result of AMR bacterial infections in 2019. If nothing changes, by 2050, 10 million people are expected to die from drug-resistant diseases every year. The message is clear: find alternative therapies or face a reality in which once-treatable infections cause once-preventable deaths." (Barron, 2022)






If you found this post interesting, please leave a comment. It would be much appreciated & would help spread the word.

The COMMENT box is at the bottom of the page, below the REFERENCES.



REFERENCES


Amazon. (2024). The Perfect Predator: A Scientist's Race to Save Her Husband from a Deadly Superbug. See: https://www.amazon.com/Perfect-Predator-Scientists-Husband-Superbug/dp/0316418080


Barron, M. (2022). Phage Therapy, Past, Present and Future. American Society for Microbiology. See: https://asm.org/articles/2022/august/phage-therapy-past,-present-and-future



Demarco, S. (March 2024). A Predatory Nature: Many species of amoebae naturally bust open biofilms to eat the bacteria inside. Now, scientists are mining these microbial predators for new ways to treat antibiotic resistant infections. DDN Exploring Drug Discovery and Development, 20:2.


Donlan, R.M. (2002). Biofilms: Microbial Life on Surfaces. Emerging Infectious Diseases, 8(9): 881–890. See:


Hardin, J.R. (2018). Manuka Honey: Delicious & Therapeutic. See: https://www.allergiesandyourgut.com/post/manuka-honey-delicious-therapeutic


Hardin, J.R. (2024). PROBLEMATIC BIOFILMS IN YOUR BODY - AND SOME THAT ARE PROTECTIVE. See: https://www.allergiesandyourgut.com/post/problematic-biofilms-in-your-body-and-some-that-are-protective


Kolodkin-Gal, I. (2023). Predation of biofilms by Parasitic Amoeba via  Exophagy. Spring NATURE Research Communities. See: https://communities.springernature.com/posts/predation-of-biofilms-by-parasitic-amoeba-via-digestive-exophagy


Kurzgesagt. (2018). The Deadliest Being on Planet Earth – The Bacteriophage. See: https://www.youtube.com/watch?v=YI3tsmFsrOg


Strathdee, S. & Patterson, T. (2019), The Perfect Predator: A Scientist's Race to Save Her Husband from a Deadly Superbug. Hachette Books.



© Copyright 2024 Joan Rothchild Hardin. All Rights Reserved.


DISCLAIMER:  Nothing on this site or blog is intended to provide medical advice, diagnosis or treatment.

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