Study On Carbohydrate-modified Antibiotics Targeting Bacterial Biofilms

Microorganisms on living or inert surfaces usually form organized multi-cell aggregates in a self-produced hydrated extracellular matrix,namely microbial biofilms.The failure in the prevention and eradiation of microbial biofilms might create a number of serious problems such as food safety(contamination)and public health issues(infectious diseases).Biofilm formation makes microbes more resistant to antibiotics when compared to planktonic cells.Thus,many researches have been carried out to investigate the well performed environmental friendly compounds against biofilm.Chitosan,the N-deacetylated derivative of chitin,is a polycationic macromolecules composed of randomly distributed β-(1-4)-linked D-glucosamine and N-acetyl-D-glucosamine.As a biomaterial,chitosan has a track record for its non-toxicity,biocompatibility and its inherent antimicrobial properties against a broad spectrum of organisms.Also,chitosan exhibits anti-biofilm activities and the ability of chitosan to damage biofilms formed by microbes.Among several mechanisms involved,chitosan has been shown to penetrate biofilms due to the ability of cationic chitosan to disrupt negatively charged cell membranes as microbes settle on the surface.The present study is to describe an innovative strategy to combat forming or preformed microbial biofilms by using chitosan as a covalent carrier for antibiotic.The conjugates are synthesized after the reduction of Schiff base formed by chitosan and streptomycin,an aminoglycoside antibiotic.Based on Chitosan-Streptomycin(C-S)Conjugates,the anti-biofilm efficiency of the conjugates was evaluated towards Gram-positive or-negative organisms.Scanning electron microscopy and fluorescence microscopy was visualized by L.monocytogenes biofilms.N-deacetylation degrees and molecular weights of the conjugate towards biofilms were studied,as well as the mechanistic insight of the biofilm.The conjugates are synthesized after the reduction of Schiff base formed by chitosan and streptomycin,an aminoglycoside antibiotic.Herein we demonstrate that conjugation of antibiotic to chitosan can efficiently damage established biofilms and inhibit biofilm formation.This method is suitable to eradiate biofilms formed by gram-positive organisms,and it appears that antibiotic contents,molecular size and positive charges of the conjugate are the key to retain this anti-biofilm activity.Mechanistic insight demonstrates chitosan conjugation renders antibiotic more accessible into biofilms,thereby available to interact with biofilm bacteria.Thus,this work represents an innovative strategy that antibiotic covalently linked to carbohydrate carriers can overcome antibiotic resistance of bacterial biofilms,and might provide a comprehensive solution to combat biofilms in industrial and medical settings.