Translating bacteriophage-derived depolymerases into antibacterial therapeutics:Challenges and prospects

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外文摘要：Predatory bacteriophages have evolved a vast array of depolymerases for bacteria capture and deprotection.These depolymerases are enzymes responsible for degrading diverse bacterial surface car-bohydrates.They are exploited as antibiofilm agents and antimicrobial adjuvants while rarely inducing bacterial resistance,making them an invaluable asset in the era of antibiotic resistance.Numerous depo-lymerases have been investigated preclinically,with evidence indicating that depolymerases with appro-priate dose regimens can safely and effectively combat different multidrug-resistant pathogens in animal infection models.Additionally,some formulation approaches have been developed for improved stability and activity of depolymerases.However,depolymerase formulation is limited to liquid dosage form and remains in its infancy,posing a significant hurdle to their clinical translation,compounded by challenges in their applicability and manufacturing.Future development must address these obstacles for clinical utility.Here,after unravelling the history,diversity,and therapeutic use of depolymerases,we summa-rized the preclinical efficacy and existing formulation findings of recombinant depolymerases.Finally,the challenges and perspectives of depolymerases as therapeutics for humans were assessed to provide insights for their further development.

外文关键词：

Phage-derived polysaccharide depolymerasesBacteriophage proteinsBacterial capsulesPolysaccharide capsulesAntibiotic resistanceBiofilmsAntibacterial therapyAntimicrobial adjuvantsCombination treatment

作者：

Honglan Wang、Yannan Liu、Changqing Bai、Sharon Shui Yee Leung

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作者单位：

School of Pharmacy,the Chinese University of Hong Kong,Hong Kong SAR,China

Emergency Medicine Clinical Research Center,Beijing Chao-Yang Hospital,Capital Medical University,Beijing 100020,China

Department of Respiratory,Shenzhen University General Hospital,Shenzhen University Clinical Medical Academy,Guangdong 518055,China

基金：

University Grants Committee,Hong Kong SAR GovernmentUniversity Grants Committee to Honglan Wang was greatly acknowledged

项目编号：

14112921

出版年：

2024

DOI：

10.1016/j.apsb.2023.08.017

药学学报(英文版)

CSTPCD

ISSN：

年,卷(期)：2024.14(1)

参考文献量100