Chitosan Microparticles Exert Broad-Spectrum Antimicrobial Activity against Antibiotic-Resistant Micro-organisms without Increasing Resistance

摘要

Antibiotic resistance is growing exponentially, increasing public health concerns for humans and animals. In the current study, we investigated the antimicrobial features of chitosan microparticles (CM), engineered from chitosan by ion gelation, seeking potential application for treating infectious disease caused by multidrug resistant microorganisms. CM showed excellent antimicrobial activity against a wide range of microorganisms, including clinically important antibiotic-resistant pathogens without raising resistant mutants in serial passage assays over a period of 15 days, which is a significantly long passage compared to tested antibiotics used in human and veterinary medicine. In addition, CM treatment did not cause cross-resistance, which is frequently observed with other antibiotics and triggers multidrug resistance. Furthermore, CM activity was examined in simulated gastrointestinal fluids that CM encounter when orally administered. Antimicrobial activity of CM was exceptionally strong to eliminate pathogens completely. CM at a concentration of 0.1 mu g/mL killed E. coli O157:H7 (5 X 10(8) CFU/mL) completely in synthetic gastric fluid within 20 min. Risk assessment of CM, in an in vitro animal model, revealed that CM did not disrupt the digestibility, pH or total volatile fatty acid production, indicating that CM likely do not affect the functionality of the rumen. Given all the advantages, CM can serve as a great candidate to treat infectious disease, especially those caused by antibiotic-resistant pathogens without adverse side effects.