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

NN researchers Asier R. Muguruza, Liqiong Li, Carlos López-Orts, Anna Laromaine, and Pablo Guardia have published a new article in the International Journal of Biological Macromolecules. This study is part of a collaboration involving the Institute of Science of Barcelon (ICMAB-CSIC, NN Group) and the University of Almería. 

The paper investigates the antimicrobial efficacy and mechanisms of action of a comprehensive library of chitosan (CS) samples varying in molecular weight (MW, from 2 to 300 kDa), functionalization (lactate and carboxymethyl groups), and biological origin (crustacean vs. fungal source). Through systematic chemical and microbiological analyses, the researchers identified that lactate-functionalized chitosan (CSlac) achieves outstanding antimicrobial performance, while 7 kDa chitosan (CS7) exhibits the best activity among pristine, unfunctionalized CS samples. The study reveals that molecular weight, surface charge, and structure critically govern colloidal stability, membrane disruption, and interactions with intracellular targets like bacterial DNA. Furthermore, in vivo biocompatibility screening using Caenorhabditis elegans demonstrated good biosafety profiles for CS7 and CSlac at therapeutically relevant concentrations, supporting their potential for sustainable biomedical applications.

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

• DOI: 10.1016/j.ijbiomac.2026.154837
  
  
  

  Abstract

  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.