Specificity and diversity of Klebsiella pneumoniae phage-encoded capsule depolymerases.

IF 5.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Max J Cheetham, Yunlong Huo, Maria Stroyakovski, Li Cheng, Daniel Wan, Anne Dell, Joanne M Santini
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引用次数: 0

Abstract

Klebsiella pneumoniae is an opportunistic pathogen with significant clinical relevance. K. pneumoniae-targeting bacteriophages encode specific polysaccharide depolymerases with the ability to selectively degrade the highly varied protective capsules, allowing for access to the bacterial cell wall. Bacteriophage depolymerases have been proposed as novel antimicrobials to combat the rise of multidrug-resistant K. pneumoniae strains. These enzymes display extraordinary diversity, and are key determinants of phage host range, however with limited data available our current knowledge of their mechanisms and ability to predict their efficacy is limited. Insight into the resolved structures of Klebsiella-specific capsule depolymerases reveals varied catalytic mechanisms, with the intra-chain cleavage mechanism providing opportunities for recombinant protein engineering. A detailed comparison of the 58 characterised depolymerases hints at structural and mechanistic patterns, such as the conservation of key domains for substrate recognition and phage tethering, as well as diversity within groups of depolymerases that target the same substrate. Another way to understand depolymerase specificity is by analyzing the targeted capsule structures, as these may share similarities recognizable by bacteriophage depolymerases, leading to broader substrate specificities. Although we have only begun to explore the complexity of Klebsiella capsule depolymerases, further research is essential to thoroughly characterise these enzymes. This will be crucial for understanding their mechanisms, predicting their efficacy, and engineering optimized enzymes for therapeutic applications.

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来源期刊
Essays in biochemistry
Essays in biochemistry 生物-生化与分子生物学
CiteScore
10.50
自引率
0.00%
发文量
105
审稿时长
>12 weeks
期刊介绍: Essays in Biochemistry publishes short, digestible reviews from experts highlighting recent key topics in biochemistry and the molecular biosciences. Written to be accessible for those not yet immersed in the subject, each article is an up-to-date, self-contained summary of the topic. Bridging the gap between the latest research and established textbooks, Essays in Biochemistry will tell you what you need to know to begin exploring the field, as each article includes the top take-home messages as summary points. Each issue of the journal is guest edited by a key opinion leader in the area, and whether you are continuing your studies or moving into a new research area, the Journal gives a complete picture in one place. Essays in Biochemistry is proud to publish Understanding Biochemistry, an essential online resource for post-16 students, teachers and undergraduates. Providing up-to-date overviews of key concepts in biochemistry and the molecular biosciences, the Understanding Biochemistry issues of Essays in Biochemistry are published annually in October.
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