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Mar. Drugs 2019, 17(1), 43;

Synthesis and Evaluation of a Chitosan Oligosaccharide-Streptomycin Conjugate against Pseudomonas aeruginosa Biofilms

University of Chinese Academy of Sciences, Beijing 100049, China
Key Laboratory of Biopharmaceutical Production & Formulation Engineering, PLA and State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China
College of Life Science, Sichuan Normal University, Chengdu 610101, China
Authors to whom correspondence should be addressed.
Received: 28 November 2018 / Revised: 30 December 2018 / Accepted: 7 January 2019 / Published: 10 January 2019
(This article belongs to the Special Issue Marine Chitin 2019)
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Microbial biofilms are considerably more resistant to antibiotics than planktonic cells. It has been reported that chitosan coupling with the aminoglycoside antibiotic streptomycin dramatically disrupted biofilms of several Gram-positive bacteria. This finding suggested the application of the covalent conjugate of antimicrobial natural polysaccharides and antibiotics on anti-infection therapy. However, the underlying molecular mechanism of the chitosan-streptomycin conjugate (CS-Strep) remains unclear and the poor water-solubility of the conjugate might restrict its applications for anti-infection therapy. In this study, we conjugated streptomycin with water-soluble chitosan oligosaccharides (COS). Unlike CS-Strep, the COS-streptomycin conjugate (COS-Strep) barely affected biofilms of tested Gram-positive bacteria. However, COS-Strep efficiently eradicated established biofilms of the Gram-negative pathogen Pseudomonas aeruginosa. This activity of COS-Strep was influenced by the degree of polymerization of chitosan oligosaccharide. The increased susceptibility of P. aeruginosa biofilms to antibiotics after conjugating might be related to the following: Suppression of the activation of MexX-MexY drug efflux pump system induced by streptomycin treatment; and down-regulation of the biosynthesis of biofilm exopolysaccharides. Thus, this work indicated that covalently linking antibiotics to chitosan oligosaccharides was a possible approach for the development of antimicrobial drugs against biofilm-related infections. View Full-Text
Keywords: chitosan oligosaccharides; streptomycin; Pseudomonas aeruginosa; biofilms; conjugation chitosan oligosaccharides; streptomycin; Pseudomonas aeruginosa; biofilms; conjugation

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Li, R.; Yuan, X.; Wei, J.; Zhang, X.; Cheng, G.; Wang, Z.A.; Du, Y. Synthesis and Evaluation of a Chitosan Oligosaccharide-Streptomycin Conjugate against Pseudomonas aeruginosa Biofilms. Mar. Drugs 2019, 17, 43.

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