Unravelling the antimicrobial mechanism of chitosan: A structure-function approach

Chitosan (CS) has emerged as a promising alternative against antimicrobial resistance due to its broad-spectrum antimicrobial properties. CS's antimicrobial activity is supposed to be influenced by its molecular weight, degree of deacetylation, chemical functionalization, and biological origin. Despite extensive research, the mechanisms underlying its bioactivity remain poorly understood, with hypotheses including membrane disruption, ion chelation, and intracellular interference. In this study, we systematically evaluated the antimicrobial efficacy and mechanisms of action of various CS samples having different molecular weight (from 2 to 300 kDa), different functionalization (carboxyl and lactate moieties) or different origin (from crustacean or fungal source). Through various chemical and microbiological assays, we identify the most effective structural features leading to the highest performance and its mechanism of action, corresponding to lactate-functionalised CS. Similarly, 7 kDa CS displays the best activity among pristine CS with different MWs. This systematic analysis offers valuable insights for the rational design of more efficient, sustainable CS-based antimicrobial therapies, contributing to developing alternative strategies against microbial infections.