18th May 2017

Standing on the Shoulders of Giants: Developing Antibiotics



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Hannah Behrens, DPhil Infection, Immunology and Translational Medicine (m.2015)

Although first discovered in 1928, it was only during the Second World War that Penicillin was developed into a drug that could cure people of bacterial diseases. This started the “antibiotic era” and is considered to be one of the most important medical discoveries of the twentieth century. Antibiotics have since been saving us from otherwise fatal bacterial diseases.

Today, nearly a century later, on the same street where penicillin was first mass-produced, another significant step in the development of antimicrobial drugs is taking place: bacteriocins antibiotics.

Over the years, extensive (ab)use of antibiotics led to bacterial resistance. Furthermore, it was found that antibiotics can cause a problem called dysbiosis. Our body contains millions of bacteria, the so-called microbiome. They fulfil many important functions which includes fighting disease-causing bacteria. When an antibiotic kills all these bacteria there is a void that can be filled by the dangerous bacteria, leading to worse diseases than before the treatment (e.g. C. difficile infection).

The onset of dysbiosis is why bacteriocins may be critical to treating bacterial infections. Bacteriocins are very specific antibiotics that kill only one kind of bacteria each, leaving the remaining microbiome intact. They bind to unique molecules on the surfaces of bacteria, trick the bacteria to take them up by disguising themselves as nutrients and finally kill them. Like traditional antibiotics some bacteriocins target transcription and cell wall synthesis, others however poke holes in the bacterium’s membrane or degrade their genetic information, their DNA or RNA.

It is known that bacteriocins are potent antibiotics in mice and pigs (and in moths), more potent in fact than conventional commercial antibiotics. There seem to be very low levels of resistance to bacteriocins and in experiments where bacteria were exposed to bacteriocins repeatedly, resistance did not emerge.

The potential for bacteriocins is huge and the field eagerly anticipates the start of human trials; a significant step forward considering some bacteria are resistant to all 26 antibiotics on the market.[1] One of the things that need to be known about any new medication before it is tested is how it works. This helps anticipate side effects. Therefore, my research focusses on unravelling the mechanism behind the most potent bacteriocin found to date:  pyocin S5.

More specifically, I investigate how is pyocin S5 is so specific in finding its target cells? How does it get into target cells to kill? Where does the energy for the entry come from? And, can bacteria inactivate bacteriocins?

While these are very specific questions, answering them will (hopefully) be the first step to opening up the whole repertoire of bacteriocins for use in patients. If bacteriocins can prevent us from falling back into the pre-antibiotic era, their arrival could be as important as the discovery of penicillin was in Sir Alexander Flemings laboratory, close to a century ago.

[1] Ashley Welch, ‘Woman died from superbug resistant to all available antibiotics in US’, 13 Jan. 2017, CBS News, http://www.cbsnews.com/news/woman-dies-from-superbug-resistant-to-all-available-antibiotic-in-u-s/.


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