As suggested by the title, these two different methods for the treatment of bacterial infections could not be more different. While antibiotics operate by ridding the body of any bacteria they may come across (good or bad), phage therapy is a process that targets just the infection-causing “bad” bacteria. Antibiotics are therefore reminiscent of a large bomb blast- there is always a specific target to take out, but the casualties are spread far and wide. Phage therapy on the other hand can be thought of as the process of employing little ninjas to sneak in and rid the body of the nasty infection-causing bacterial cells, with no other cells being affected.
But first, antibiotics:
Antibiotics are medicines, either naturally occurring or semi-synthetic, which inhibit the growth of microorganisms, specifically bacteria, thus allowing the antibodies of the host to kill off the infection-causing bacterial cells. Antibiotics are administered in liquid form, as tablets, in the form of creams and even through IV (intravenous) therapy in the case of more extreme infections. The problem with antibiotics is that they are not able to tell the difference between “good” and “bad” bacterial cells, and so they end up affecting the growth of important bacteria, such as those in the gut of mammals, and hence probiotics must often be taken simultaneously.
From what I have read on various websites, I think that it would be quite accurate to assume that most people in the Western world have either heard of antibiotics or have taken antibiotics or both. The discovery of the very first antibiotic, Penicillin, happened in 1928 and was discovered by Alexander Fleming. After many years of research, in 1943 Penicillin became available for widespread production and clinical use. Other antibiotic discoveries followed in 1943, 1947 and 1952, the Golden Age of antibiotic discovery in the 1940’s to 1950’s seeing many new natural antibiotics being isolated from soils. However in 1948 Penicillin-resistant strains of Staphylococcus aureus had already been circulating and a global pandemic followed between the years of 1948-1962. This should have been a clear warning of the dangers of the ever-evolving tendencies of bacteria. But, in 1960, Methicillin was introduced for chemical use- the first semi-synthetic penicillin derivative. By 1962, just 2 years later, there were already clinical strains of methicillin-resistant Staphylococcus aureus appearing. There is an interesting timeline here that extends on the topic of antibiotic discovery, but a common trend you will see is that many bacterial strains develop antibiotic resistance, and this is a serious problem.
There was recently an article in the Washington Post, detailing the arrival of the “superbug” in the U.S., a strain of E.coli (seen in the image below) found to be resistant to the antibiotic colistin. This antibiotic has been known as a “last-resort” drug, that can have serious adverse side effects and which is usually administered in the case of especially tenacious bacterial infections resulting from multi-drug resistant bacteria. The deaths associated with multi-drug resistant bacterial infections is on the rise, and As more drug-resistant strains of bacteria emerge, we get closer and closer to the end of the antibiotic-era, and the exploration of alternative treatments is becoming essential.
The reason why these drug-resistant strains emerge in the first place, is usually as a result of two scenarios: one, the antibiotics are prescribed long before they are necessary, in a stage where the antibodies of the host could still fight off the infection Or two, the antibiotics are not taken correctly- that is, people stop taking the antibiotic when the infection appears to have subsided. Either way, the bacterial cells are provided with the opportunity to become resistant when we don’t succeed in killing off every individual cell. And given the rapid growth rate of bacterial colonies, it doesn’t take long before the surviving individuals multiply, passing on the drug-resistance gene to their offspring.
Now, Phage Therapy:
Given the situation we find ourselves in, exploration of alternative treatments is of great importance. And to give you a bit more of an introduction to the ideas behind the existing alternative to antibiotics, watch this clip (by our very own Dr Heather Hendrickson!) about the “Microbial ninjas” we call bacteriophages, just like the one seen in the image above.
Phage therapy was widely used in the United States, former Soviet Union and Western Europe in the 1920’s and 1930’s, until the discovery of antibiotics resulted in the abandonment of phage research in the U.S and Western Europe. In the countries of the former Soviet Union, phage therapy and research is ongoing. Most notably in the country of Georgia, where the Phage Therapy Centre is found in Tbilisi (see the map below).
The link provided will take you straight to their website, which has LOTS of in-depth information regarding phage therapy practices, so take a look if you like.
The beauty of phage is that they are specific to the bacteria they infect, and so they will not harm the “good bacteria” in the host body suffering from a bacterial infection. It is of course by chance that phage infecting a specific bacteria are found, but that is why continuous research is necessary, and also so that in the case of bacteria developing resistance to one phage, another may be ready and waiting to take its place. And due to the estimated abundance of phage on Earth- about 10^31 phage- the chances of finding more than one phage infecting the same bacteria are quite high. The phage are of course naturally occurring, and so are much cheaper to “produce” in large quantities than antibiotics.
Although it is necessary to isolate and purify phage before administration, there are much-researched and straight forward ways of doing this. The purified phage with a specific, known titer can be administered through liquid preparations, tablets and also in the form of dressings for infected wounds, and may be given in conjunction with antibiotics if the infection is particularly persistent. The most successful use of phage is in the treatment of gastrointestinal infections and those infections associated with open wounds or burns.
In summary, these sneaky ninjas called phages have a lot of potential for success, as has been proved by the treatment carried out in Georgia for all of these years. This so-called “forgotten medicine” has all the makings of a successful alternative to antibiotics, although it may need to be more rigorously studied here in New Zealand before it is recognised as safe to use on people and animals to treat infections.
To conclude this blog post, I’d like to introduce you to my phage, Phage PlainJane. This link has all of the details outlining where this phage was captured, tamed and finally dissected to get a better look at it, as found on the PhagesDB.org website. From the EM image, she may just appear to be a regular siphoviridae phage, as is common in phage isolated using Mycobacterium smegmatis, but who knows what’s on the inside? Potential can often be found in the most unexpected places. And regardless of the whether or not PlainJane is something special scientifically speaking, “she” will always be special to me- a symbol of this extremely rewarding and oddly fulfilling process of finding and naming a new, unique organism (no matter how small).
It is now an experience that has been ticked off, before it had even appeared on my bucket list!
√ Discover a new, unique (tiny, ninja) organism.
Goodluck to all the future phage-hunters, I hope you enjoy the journey as much as I did.
All the best,