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

Predatory bacteriophages have evolved a vast array of depolymerases for bacteria capture and deprotection. These depolymerases are enzymes responsible for degrading diverse bacterial surface carbohydrates. They are exploited as antibiofilm agents and antimicrobial adjuvants while rarely inducing bac...

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Published inActa pharmaceutica Sinica. B Vol. 14; no. 1; pp. 155 - 169
Main Authors Wang, Honglan, Liu, Yannan, Bai, Changqing, Leung, Sharon Shui Yee
Format Journal Article
LanguageEnglish
Published Elsevier B.V 01.01.2024
Elsevier
Subjects
Antibacterial therapy
Antibiotic resistance
Antimicrobial adjuvants
Bacterial capsules
Bacteriophage proteins
Biofilms
Combination treatment
Phage-derived polysaccharide depolymerases
Polysaccharide capsules
Review
Combination treatment
Biofilms
Antibiotic resistance
Antimicrobial adjuvants
Bacteriophage proteins
Phage-derived polysaccharide depolymerases
Antibacterial therapy
Polysaccharide capsules
Bacterial capsules
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Abstract Predatory bacteriophages have evolved a vast array of depolymerases for bacteria capture and deprotection. These depolymerases are enzymes responsible for degrading diverse bacterial surface carbohydrates. 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 depolymerases have been investigated preclinically, with evidence indicating that depolymerases with appropriate 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 summarized 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. Phage-derived polysaccharide depolymerases are useful as antibiofilm agents and antimicrobial adjuvants. Their preclinical efficacy was reviewed, and their challenges and prospects for clinical translation were discussed. [Display omitted]
AbstractList Predatory bacteriophages have evolved a vast array of depolymerases for bacteria capture and deprotection. These depolymerases are enzymes responsible for degrading diverse bacterial surface carbohydrates. 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 depolymerases have been investigated preclinically, with evidence indicating that depolymerases with appropriate 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 summarized 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.
Predatory bacteriophages have evolved a vast array of depolymerases for bacteria capture and deprotection. These depolymerases are enzymes responsible for degrading diverse bacterial surface carbohydrates. 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 depolymerases have been investigated preclinically, with evidence indicating that depolymerases with appropriate 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 summarized 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. Phage-derived polysaccharide depolymerases are useful as antibiofilm agents and antimicrobial adjuvants. Their preclinical efficacy was reviewed, and their challenges and prospects for clinical translation were discussed. Image 1
Predatory bacteriophages have evolved a vast array of depolymerases for bacteria capture and deprotection. These depolymerases are enzymes responsible for degrading diverse bacterial surface carbohydrates. 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 depolymerases have been investigated preclinically, with evidence indicating that depolymerases with appropriate 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 summarized 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. Phage-derived polysaccharide depolymerases are useful as antibiofilm agents and antimicrobial adjuvants. Their preclinical efficacy was reviewed, and their challenges and prospects for clinical translation were discussed. [Display omitted]
Author Wang, Honglan
Liu, Yannan
Leung, Sharon Shui Yee
Bai, Changqing
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Issue 1
Keywords Combination treatment
Biofilms
Antibiotic resistance
Antimicrobial adjuvants
Bacteriophage proteins
Phage-derived polysaccharide depolymerases
Antibacterial therapy
Polysaccharide capsules
Bacterial capsules
Language English
License This is an open access article under the CC BY-NC-ND license.
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Snippet Predatory bacteriophages have evolved a vast array of depolymerases for bacteria capture and deprotection. These depolymerases are enzymes responsible for...
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StartPage 155
SubjectTerms Antibacterial therapy
Antibiotic resistance
Antimicrobial adjuvants
Bacterial capsules
Bacteriophage proteins
Biofilms
Combination treatment
Phage-derived polysaccharide depolymerases
Polysaccharide capsules
Review
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Title Translating bacteriophage-derived depolymerases into antibacterial therapeutics: Challenges and prospects
URI https://dx.doi.org/10.1016/j.apsb.2023.08.017
https://www.proquest.com/docview/2929058769
https://pubmed.ncbi.nlm.nih.gov/PMC10792971
https://doaj.org/article/29bad491904f4378b40f78575015341a
Volume 14
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