Synthesis and pharmacological optimization of bacteriocins and lipopeptides for the development of new antimicrobial agents

Éric Biron

CHU de Québec, Université Laval, Quebec, Canada

The increase of antibiotic resistance and its spread raise a major challenge for preventing and treating bacterial infections. Due to this critical public health problem and limited treatment options, the development of innovative antimicrobial agents and new alternatives to antibiotics is crucial, and this has become a high priority worldwide. One promising approach has been searching for antimicrobial agents of bacterial origin, such as bacteriocins and lipopeptides. These peptides show very interesting properties such as high activity, original modes of action, various spectra of action and low cytotoxicity. Despite their huge potential in the agri-food and medical sectors, the use of these peptides remains limited due to difficulties associated with their production and/or stability.

To overcome these limitations, our team uses a combination of synthetic and peptidomimetic approaches to produce peptides, study structure-activity relationships and develop analogues with improved pharmacological properties and stability. As a result of applying this approach to the pediocin PA-1, we have been able to develop an efficient synthesis path suitable for large-scale production and to conduct structure-activity studies in order to develop an analogue with enhance stability.  Health Canada approved the latter in May 2020 for use as a technological agent in the food sector. Based on this success, the strategy has been applied to other antimicrobial bacteriocins and lipopeptides. The complete synthesis and the results of structure-activity studies of the bacteriocins pediocin PA-1 and bactofencin A, and of the lipopeptides humimycin and glycinocin will be discussed.