Studies on the mechanisms of action and development of resistance to class II bacteriocins of Gram-positive bacteria

Bacteriocins are peptides or proteins produced by bacteria to kill or inhibit the growth of other bacteria inhabiting the same ecological niche. The growing interest in bacteriocins reflects their potential use in food preservation and treatment of infections caused by antibiotic-resistant pathogenic bacteria, among other applications. The number of published studies on the identification of new bacteriocin-producing strains is constantly increasing. At the same time, there is a noticeable lack of research describing the mechanisms of action of most newly identified bacteriocins, as well as the mechanisms leading to the development of resistance to these bacteriocins and cross-resistance to antibiotics. Detailed understanding of these issues will allow to develop guidelines ensuring the most effective, safe and long-term use of bacteriocins without the risk of resistance development. This work describes the main assumptions of the doctoral dissertation of Aleksandra Tymoszewska, which objectives were to characterize the mechanisms of action and of resistance to class II bacteriocins of Gram-positive bacteria. Using the model bacterium Lactococcus lactis, two groups of bacteriocins were examined: (i) garvicins Q, A, B and C, and BacSJ; and (ii) aureocin A53 (AurA53)- and enterocin L50 (EntL50)-like bacteriocins. Bacteriocins of group (i) have been shown to recognize susceptible cells and form pores in the cell membrane using a specific receptor, the mannose-specific phosphotransferase system (Man-PTS), and sensitive bacteria have been shown to acquire resistance to the these bacteriocins by modifying the structure of Man-PTS. On the other hand, the acquisition of resistance to group (ii) membrane-targeting and receptor-independent bacteriocins occurs through changes in the structure of the bacterial cell wall and membrane, which are induced by changes in the expression of proteins involved in lipid metabolism or components of the YsaCB-KinG-LlrG regulatory system. The results shed new light on previous views on the mechanisms of action of bacteriocins and open up opportunities for their further study.