Every IITM student writes a review shortly after starting their PhD project. Often this is about the literature directly relevant to their thesis. In my case it was different; a very good recent review about the background to my thesis already existed. Instead I decided to have a look at how the toxins I study could be transformed into medicine.
Bacteriocins, the toxins I study, are not toxic to humans but instead very specifically kill certain species or strains of bacteria. The bacteriocin most of my work focuses on, for example, is produced by a bacterium called Pseudomonas aeruginosa to kill other strains of the same species; its cousins, if you wish. This way they can defend or conquer ecological niches. Can we exploit these bacteriocins as antibiotics to treat bacterial diseases in humans?
Searching for evidence
Last summer I set out to find all the reports of people who had tried these bacteriocins to cure infections in animals. I found eleven such reports and two additional ones which just looked at the effect of bacteriocins in healthy animals. Finding these reports was the most difficult part of all. Most reports I read turned out to be irrelevant. One I had to request from the libraries’ archives. It was so old it only existed on paper, as compared to most scientific reports which can now be found online. I went up to the top floor of the Bodleian library in Oxford where I received an old linen-bound book.
Of the eleven studies I found, only six, all from this century, had actually identified the exact bacteriocin they worked with. Previously researchers had realized they were working with something toxic but were not yet able to identify it.
Next I analysed the data I had found. It looked very promising. In all cases the bacteriocins were able to resolve or reduce bacterial infections – something that keeps me motivated on days when my research is not that easy!
Better than traditional antibiotics?
One question you might have asked yourself is, but why do we even need new antibiotics? Don’t we already have many? We have 26 but our frequent (over)use during the last century has led to many bacteria developing resistance. In the past few years more and more cases of bacteria resistant to all antibiotics occurred. Meanwhile the development of traditional antibiotics has stalled since the last major discovery of a new drug back in 1987. Scientists are now turning to an array of alternative antibiotics to plug the growing gap. One very promising type are narrow-spectrum antibiotics, such as bacteriocins.
Bacteriocins only kill one species of bacteria or even a subset of that species. This is in contrast to traditional antibiotics which kill a wide range of bacteria. I like to think about it like this: Something as different from you as a tree, causes a disease. Nonetheless you are wiped out with it because you happen to belong to the same kingdom of life as the tree. This is exactly how broad the spectrum of traditional antibiotics is. Bacteriocins however have such a narrow spectrum they can differentiate between you and your cousin (figuratively speaking).
The disadvantage following from that is that one needs to identify the species and maybe even strain of bacteria causing an infection before starting the treatment. The huge advantage is however that only those bacteria that cause the infection are treated. Because traditional antibiotics kill all types of bacteria they also select for resistant mutants in all types of bacteria. With narrow spectrum antibiotics only one species out of the millions we carry in our body is put under selective pressure. (Selective pressure kills most but encourages the spread of resistant survivors). This way, narrow spectrum antibiotics, such as bacteriocins, do not promote antibiotic resistance.
The broad killing spectrum of traditional antibiotics also means that the delicate balance of health-related “friendly” bacteria in our body gets disturbed. Especially in elderly and weak people this can have devastating, even lethal effects, such as promoting C. difficile infections. The beauty of narrow spectrum antibiotics is once again that they leave all bacteria that are not related to the infection unaffected.
These aspects and some others which will determine the success of bacteriocins as antibiotics I have discussed in the second part of my review article. Especially helpful for this part was my Co-author Dr. Anne Six from Glasgow. Together we polished the article until we decided it was ready to submit. After incorporating some advice from the reviewers our review has finally been published. You can now read it here.
Author: Hannah Behrens
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Behrens, H.M., Six, A., Walker, D. and Kleanthous, C. (2017) The therapeutic potential of bacteriocins as protein antibiotics. Emerging Topics in Life Sciences. 1(1) 65-74