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Phage Phenomics: Physiological Approaches to Characterize Novel Viral Proteins
Published on: June 11, 2015
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Friunavirus Phage-Encoded Depolymerases Specific to Different Capsular Types of Acinetobacter baumannii
Olga Y Timoshina1,2, Anastasia A Kasimova3, Mikhail M Shneider1
1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.
International Journal of Molecular Sciences
|May 27, 2023
Summary
Researchers characterized novel tailspike depolymerases (TSDs) from Friunaviruses that degrade Acinetobacter baumannii capsular polysaccharides (CPSs). These TSDs show potential as antibacterial agents against this critical nosocomial pathogen.
Area of Science:
- Microbiology and Virology
- Structural Biology
- Biochemistry
Background:
- Acinetobacter baumannii is a critical priority nosocomial pathogen.
- Bacterial capsular polysaccharides (CPSs) are key receptors for phage depolymerases.
- Phage-derived enzymes offer potential as novel antibacterial agents.
Purpose of the Study:
- To characterize tailspike depolymerases (TSDs) from novel Friunaviruses targeting Acinetobacter baumannii CPSs.
- To elucidate the mechanism of CPS cleavage by these TSDs.
- To explore the therapeutic potential of TSDs against A. baumannii infections.
Main Methods:
- Genomic analysis of six novel Friunaviruses and one known Friunavirus.
- Characterization of recombinant TSDs for specific cleavage of A. baumannii CPSs.
- Determination of oligosaccharide fragment structures after CPS degradation.
- X-ray crystallography of three TSDs.
- In vivo efficacy testing in Galleria mellonella infection models.
Main Results:
- Mechanism of specific CPS cleavage by all characterized TSDs was established.
- Structures of oligosaccharide fragments from degraded CPSs (K9, K14, K16, K37/K3-v1, K86, K127, K128) were determined.
- Crystal structures of three TSDs were obtained.
- Recombinant TSD APK09_gp48 significantly reduced mortality in Galleria mellonella infected with K9-type A. baumannii.
Conclusions:
- The study provides a detailed understanding of Friunavirus TSDs and their interaction with A. baumannii CPSs.
- These findings contribute to the rational application of lytic phages and phage-derived enzymes as antibacterial strategies.
- TSDs represent promising candidates for developing novel therapeutics against Acinetobacter baumannii infections.
Keywords:
Acinetobacter baumanniibacteriophagecapsular polysaccharidecapsular typecrystal structureglycosidasetailspike depolymeraseMore Related Videos
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