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Bacteriocins are small, ribosomally-produced peptides with antimicrobial properties. They are typically described as having a very narrow specificity, often targeting similarly related bacterial species or strains. Some bacteriocins have a wide spectrum of activity, as we have observed in concurrence with the literature. These molecules have great potential for industrial applications.
The video below illustrates how bacteriocins can affect bacterial growth. The top video shows normal growth of E. coli (two hours of growth in LB medium followed by eight hours in a solution WITHOUT bacteriocins). The bottom video shows E. coli grown in the same conditions, but in a solution WITH bacteriocins. (time-lapsed microscopy combined with microfluidic device of the Cellular and Molecular Microbiology lab at ULB)
The history of bacteriocins begins with the Belgian scientist André Gratia. In 1925, as an early result of a search for bacteria with antimicrobial properties, Gratia described the activity of colicin, the first known bacteriocin. This discovery happened concurrently with Alexander Fleming’s description of the antibiotic penicillin in 1928 and the independent observations of bacteriophage activity by Frederick Twort in 1915 and Félix d’Hérelle in 1917.
Bacteriocins did not receive the same level of attention as antibiotics, as a lack of understanding of their biology led to difficulties in their production and low consistency in controlling microbial growth. This led to the dominance of chemically synthesized broad-spectrum antibiotics for the rest of the 20th century up to the present. Similar issues were observed with bacteriophages, although they have found extensive medical use in the country of Georgia through the work of d’Hérélle and George Eliava, as well as in Russia and Poland The use of bacteriophages in the dairy industry has also been commercialized in the US and the Netherlands.
Currently, bacteriocin use is most often associated with the food industry. Many bacteriocins are produced by Gram-positive species, particularly lactic acid producing bacteria such as Lactoccocus sp. Nisin is the most widely used of these bacteriocins, acting as a food preservative, and has GRAS (generally recognized as safe) status from the FDA and is approved as preservative (food additive) in the European Union (E234).
Antimicrobial resistance (AMR)
The emergence of antimicrobial resistance (AMR) has great negative implications for human health. The reduction of antibiotic use in medical and industrial applications should be a common goal to reduce the amount of antibiotics released into the environment. Bacteriocins offer a promising approach to solving this problem. Additionally, avoiding the use of antibiotics in industrial applications of biofermentors can reduce production costs and help focus metabolic output on production.
New developments in academic research
Bacteriocins are also known to play a role in bacterial communication and ecology. For example, the gut and oral cavity are parts of the human body that accommodate thousands of different bacterial species. These bacteria, often beneficial for human health, are continuously in a stressful environment and compete for food and space. When he was researcher in Prof. Pascal Hols lab (UCL/LIBST), Dr. Johann Mignolet (now R&D Project Manager of Syngulon) demonstrated that Streptococcus salivarius, a commensal human gut bacterium, uses a communication pheromone to concomitantly trigger two responses: the ability to modify its genome via the acquisition of “foreign” DNA and the production of potent bacteriocins. These toxins or non-transformable variants of S. Salivarius could be used for medical purposes to kill harmful multi-resistant superbugs such as Staphylococcus aureus and several streptococci (Mignolet et al 2018; PMID: 29444418; DOI: 10.1016/j.celrep.2018.01.055).
This figure adapted from Mignolet et al, 2018, shows the different transcriptional cascades that trigger competence entry and expression of bacteriocin–encoding genes in four different streptococci models: S. salivarius, S. thermophilus, S. mutans and pneumoniae. Specifically interesting is that the BlpRH/BlpC bacteriocin regulatory system is missing or incomplete in S. Salivarius. The boxes show systems shared between species. Large continuous arrows depict transcriptional control, and dashed arrows display protein translation. Small continuous arrows indicate protein/peptide/phosphate motion.
The bacterium-killing assay below demonstrates addition of a pheromone inducing bacteriocin production, which leads to an inhibitory effect on surrounding bacteria.
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