Bacteria are increasingly resistant to antibiotics. Today, some of these microbes are even completely impervious. The search for alternatives is urgent. Dr Johann Mignolet, visiting researcher from Syngulon, studies bacteriocins as molecules that can replace or complement antibiotics.
According to the World Health Organization (WHO), ‘Antibiotic resistance is one of today’s most serious threats to global health, food security and development’. Antibiotics, used to treat and prevent certain bacterial infections, lose their effectiveness because bacteria become resistant. As a result, treating infections in humans and animals becomes more difficult. Dr Johann Mignolet, an R&D project manager at Syngulon and visiting researcher at the Louvain Institute of Biomolecular Science and Technology (LIBST), is one of many researchers seeking new strategies to address the problem. Syngulon is a synthetic biology startup developing original genetic technologies to rejuvenate bacteriocins. It is a “Startup in the labs” meaning that the members of Syngulon’s team perform their researches directly in partner labs (e.g. UCLouvain, ULiège, ULB and University College of London).
Bacteriocin. A star molecule
For the past few years, Dr Mignolet has focused on bacteriocins as a new antimicrobial solution to multidrug resistance. These antibacterial molecules of the protein family, which are synthesized naturally by certain bacteria, represent an interesting alternative or complement to antibiotics. Better yet, they could restore the former strength of antibiotics, which has been lost owing to the multiplication of multidrug resistant bacterial strains. In other words, bacteriocins are not antibiotics but have antibiotic properties, such as the bactericidal capacity to eliminate certain microorganisms or the bacteriostatic capacity to inhibit the growth of certain microorganisms. It is therefore the ideal candidate for a solution to the problem of multidrug resistance.
Bacteriocins have many advantages. First, techniques for producing them are many and varied. On an industrial scale, the cost of producing bacteriocins decreases from month to month and may become less than the cost of producing antibiotics. It would also be possible to use the bacteria present in our intestinal flora to produce bacteriocins in the gut and thus treat some intestinal bacterial infections. In addition, the proposed solution to the problem of multidrug resistance does not rely solely on the use of one bacteriocin but on the development of a mixture of several bacteriocins. The probability that an escape mechanism (and thus multidrug resistance) can be created against several bacteriocins is much lower than against a single antibiotic. Using ‘bacteriocin cocktails’ with totally different and specialized modes of action (which kill only one particular type of bacterium) would mean any resistance would emerge less quickly. Currently, the main disadvantage of bacteriocins is their protein base. First, they are the target of proteases, that is, proteins that break down other proteins. Second, by administering certain bacteriocins in the human body, the immune system may respond.
From industry to medicine
Dr Mignolet now wants to show that we can draw from this stock of new antimicrobial molecules for a variety of applications. All have a common goal: to kill the problematic bacteria. In the industrial field, bacteriocins can kill microorganisms that disturb the fermentation process. This is the case when producing bioethanol, for example. In the longer term, in the (human and animal) medical field, bacteriocins could target certain strains in the skin or intestine and replace or complement antibiotics.
Today, Dr Mignolet continues his research to better understand how to trigger the production of bacteriocins in gut bacteria for treating certain bacterial infections. Specifically, he intends to use small molecules called pheromones to hack the production system and activate it on demand. A collaborative patent between UCLouvain and Syngulon safeguards these discoveries. Syngulon is building a unique in-house bacteriocin collection based on a synthetic DNA library. In the coming years, Syngulon and Dr Mignolet will continue to determine the bacteria targeted by bacteriocins. On this basis, they would like to build a pool of effective bacteriocins. These can be used in combination (“cocktails”) to finely adjust microbial community composition. They are working on pathogenic bacteria from the WHO's list, such as Staphylococcus aureus and the tuberculosis agent, which represent prime targets for medical development. Subsequent steps will be defining whether the use of bacteriocins in the industrial world is economically viable, verifying that ‘bacteriocin cocktails’ are non-toxic, and gaining medical approval.
A glance at Dr Johann Mignolet's bio
Dr Johann Mignolet studied biology at the University of Namur before completing a PhD in molecular biology at the same university under the supervision of Prof. Xavier De Bolle. He was a postdoctoral researcher at ULB in 2009, at the University of Geneva in 2010, and at UCLouvain (under the supervision of Prof. Pascal Hols, LIBST) in 2013. Throughout his academic career, he has tried to understand how bacteria perceive their environment as well as the behaviours they develop to adapt to it. Today, Dr Mignolet is R&D project manager at Syngulon and a visiting researcher at UCLouvain. He follows an applied approach to his research on bacteriocins.