High molecular weight chitosan oligosaccharide exhibited antifungal activity by misleading cell wall organization via targeting PHR transglucosidases

Ruilian Li; Limeng Zhu; Dongdong Liu; Wenjing Wang; Chen Zhang; Siming Jiao; Jinhua Wei; Lishi Ren; Yuchen Zhang; Xun Gou; Xianghua Yuan; Yuguang Du; Zhuo A Wang

doi:10.1016/j.carbpol.2022.119253

High molecular weight chitosan oligosaccharide exhibited antifungal activity by misleading cell wall organization via targeting PHR transglucosidases

Carbohydr Polym. 2022 Jun 1:285:119253. doi: 10.1016/j.carbpol.2022.119253. Epub 2022 Feb 19.

Authors

Ruilian Li¹, Limeng Zhu¹, Dongdong Liu², Wenjing Wang³, Chen Zhang¹, Siming Jiao², Jinhua Wei¹, Lishi Ren², Yuchen Zhang², Xun Gou⁴, Xianghua Yuan⁴, Yuguang Du⁵, Zhuo A Wang⁶

Affiliations

¹ University of Chinese Academy of Sciences, Beijing 100049, China; State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
² State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
³ 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.
⁴ College of Life Science, Sichuan Normal University, Chengdu 610101, China.
⁵ University of Chinese Academy of Sciences, Beijing 100049, China; State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China. Electronic address: [email protected].
⁶ University of Chinese Academy of Sciences, Beijing 100049, China; State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China. Electronic address: [email protected].

PMID: 35287867
DOI: 10.1016/j.carbpol.2022.119253

Abstract

The fungal cell wall is an ideal target for the design of antifungal drugs. In this study we used an analog of cell wall polymer, a highly deacetylated high molecular-weight chitosan oligosaccharide (HCOS), to test its effect against pathogenic Candida strains. Results showed that HCOS was successfully incorporated into the dynamic cell wall organization process and exhibited an apparent antifungal activity against both plankton and mature fungal biofilm, by impairing the cell wall integrity. Unexpectedly, mechanistic studies suggested that HCOS exerts its activity by interfering with family members of PHR β-(1,3)-glucanosyl transferases and affecting the connection and assembly of cell wall polysaccharides. Furthermore, HCOS showed great synergistic activity with different fungicides against Candida cells, especially those in biofilm. These findings indicated HCOS has a great potential as an antifungal drug or drug synergist and proposed a novel antifungal strategy with structure-specific oligosaccharides mimicking cell wall polysaccharide fragments.

Keywords: Biofilm; Candida albicans; Cell wall; Chitosan oligosaccharide; PHR transglucosidases.

MeSH terms

Antifungal Agents* / pharmacology
Biofilms
Candida albicans
Cell Wall
Chitosan* / pharmacology
Microbial Sensitivity Tests
Molecular Weight
Oligosaccharides / pharmacology

Substances

Antifungal Agents
Oligosaccharides
Chitosan