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Mar. Drugs 2019, 17(1), 43; https://doi.org/10.3390/md17010043

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

1
University of Chinese Academy of Sciences, Beijing 100049, China
2
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
3
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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Abstract

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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