Inhibition Zones, microbial growth

The age of phage?

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I have run into this problem since grad school. What’s the plural of virus? Is it viri? Virus? Viruses?

Oh, I know what American lexicographers claim, but there is no universal answer to this query. (I tend to use viri or virus.) By the way, virion is not a single virus particle, rather it describes the virus after it has morphed into its vector stage.  (That is when it is absolutely ready to infect a host cell; you do remember that viri are absolute parasites, in that they are only “alive” when they have joined with an infected cell.)

The same applies to a specific virus particle called a bacteriophage. The plural is either bacteriophage or bacteriophages. And, just to make sure, you recall that bacteriophage are virus particles that only infect bacterial cells, not animal cells.

So much for science being an absolute….

And, bacteriophage were first identified a century ago (1915) by Frederick Twort. Actually, Twort noticed that when bacteria invaded his viral cultures, they disappeared after a short period of time. Two years later, Felix d’Herelle noticed the same thing. d’Herelle thought the virus was eating the bacteria so he called them bacteriophage (the term does means ‘bacteria eater’). Except, the virus didn’t eat the bacteria- it infected the microbes and destroyed them.

Now, had technology been available, maybe bacteriophage research would have expanded to discern ways to protect humans from bacterial infections. But, within a decade of discovering the phages, antibiotics were being discovered- and the antibiotic heyday continued until the mid-1980s. Antibiotics were typically found by sampling the environment, finding places or situations where bacteria couldn’t grow, refining the process, and then offering the antibiotic to the public.

The year I was born, Bristol-Myers included a pre-addressed envelope in its annual report asking every shareholder to collect a teaspoon of soil (‘preferably moist, but not wet’), sans stones, and place it in the envelope. Eli Lilly tried a similar approach with missionaries traveling to third world countries, requesting them to collect samples in test tubes. Pfizer hit up pilots and foreign correspondents to collect soil samples. All  of these phamaceutical firms were hoping to discover the next big thing in antibiotics.

A decade later, this approach had pretty much passed its zenith.  So, the era of synthetic production began. (Ah, the age of chemical engineering and industrial microbiology.) A decade later still and pharmaceutical firms were unable to discern any new classes of antibiotics; which is one reason why we are having a hard time treating humans infected by bacteria.

We’ve also over-prescribed antibiotics (especially for animal feeding )- which effects are exacerbated as many folks simply do not follow the required protocol, stopping their pills, so that bacteria learn how to “adjust” to antibiotic levels. And, now, bacteria are almost fully resistant to our drugs. So much so that WHO (The World Health Organization) proclaims that bacterial resistance is “one of the biggest threats to global health, food security, and development today”.

Given today’s alternative fact syndrome, you should know that about 700,000 folks die EVERY year from drug-resistant infections. If we don’t solve this problem it could grow almost 100 fold in 30 years (about 10 million).

Which is why pharma is grasping onto phage therapy. Using old studies, but with new knowledge and subject to new technological processes. However, the FDA (Food and Drug Administration) has not approved any bacteriophage treatments- but they’ve let some small trials (for deathly ill patients) proceed. And, the FDA is considering the design of clinical trials to enable approvals.

The good thing is that bacteriophage are ubiquitous. They are the most prevalent type of virus. They may even be the most populous organism (of sorts) on earth. And, since they are particular to bacteria, they theoretically should present little threat to humans.

(Yes, they are found in our gastrointestinal (GI) tract, too. And, you do recall that microbial flora in our GI tract are responsible for most of our digestion.)

Moreover, antibiotics are blunderbuss instruments- they tend to kill off whole classes of microbes. (This is why you should take active culture yogurt while under an antibiotic regimen, to ensure your GI tract doesn’t go haywire and you are then subject to all sorts of other medical problems). But, again, bacteriophage are specific- to a single species of bacteria. And, once they find their target, they infect, replicate, force the host to rupture, yielding additional copies of the bacteriophage to attack the same species again and again.

Now, because bacteriophage are specific, that is also the problem. Because we need to find the RIGHT bacteriophage for a given infection. That means it’s back to the way I found bacteria to treat HGSW (Honest-To-Goodness-Solid-Waste, read as garbage) and other searches some 40 years ago.

Inhibition Zones, microbial growth

We take the antibiotic resistant microbe and grow it on a nutrient agar (or specialized agar that promotes the growth of this particular microbe) plate. Then, the plates are subjected to various bacteriophage to see which, if any, kill the bacteria. (The dead bacteria are noted as “holes” in the growth of bacteria on the plate.)

Next, we have to scale up the production of the phages (which will require them growing on these microbes in a culture) and then discern how to administer the phage to the patient. (Orally? Topically? Via Aerosol to the respiratory tract? Or, via IV [intravenous]?)

If we are lucky, this process takes 5 days- maybe 10, maybe 20. And, we have to hope the patient survives until we find and grow the right bacteriophage.

Which means, we scientists/engineers must find much quicker ways and better processes to speed up this screen and response.

Another wrinkle. (Or, is that a wet blanket?) Bacteria can also develop resistance to bacteriophage. So, we probably will have to develop a cocktail of different phages to ensure the microbe succumbs. (Note: This is akin to why HIV subjects take cocktails of drugs- and it’s why they are now not rapidly dying off.)

(I’m going to skip the issue of bacteriophage transferring genetic matter from one bacteria to another. These type of bacteriophage are called lysogenic phages. And, given their traits, we can’t administer such phage to humans.)

We may be in for another heyday in eradicating bacterial infections, once again.

Keep your fingers crossed.Roy A. Ackerman, Ph.D., E.A.

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12 thoughts on “The age of phage?”

  1. Quite an interesting topic and in fact antibiotics are used at large and for prevention????????? which I don’t like. It could be a good question for debate however it is a scientific subject to discuss If we don’t have the knowledge! Good day!

    1. I am SO sorry, Martha!!!! I tried hard to keep the subject matter direct enough so that everyone can comprehend the matter.
      I would ABSOLUTELY appreciate it if you could let me know exactly where I lost you. I won’t let it happen again!

  2. Hmmm, yes, people think that they are better and stop taking their antibiotics, but then discover that was a bad idea. It was always impressed upon me that I had to finish the prescription, and I was taught how to keep records so that I would not forget my pills!

  3. Interesting, Roy. When I first heard about some bacteria being resistant to antibiotics, I couldn’t believe it. An incident with my daughter led me to believe.

    This is very informative. 🙂

  4. I recently heard the same – that we’ve over prescribed our antibiotics and meds so much that virus’ have become immune to them, and soon there’ll be large plagues of people with illnesses we can’t medicate. Will be interesting to see what new medicine from old knowledge brings.

    1. Actually, Megan, antibiotics only work on bacterial infections. And, that’s yet another problem. Too many practitioners give in to the demands of patients who want a prescription- even if their ailment is viral!

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