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Published on: January 5, 2024
Identifying phage Lysins through genomic analysis of prophages from Acinetobacter baumannii
Maria Leonor Raposo1,2, Ana Carolina Pimentel1,2, Vera Manageiro3,4,5
1Faculdade de Ciências, BioISI - Instituto de Biossistemas e Ciências Integrativas, Universidade de Lisboa, Lisbon, Portugal.
Abstract:
Acinetobacter baumannii is a Gram-negative opportunistic pathogen, responsible for nosocomial infections worldwide. In recent years, this microorganism has acquired resistance to various antibiotics, prompting the World Health Organization (WHO) to declare carbapenem-resistant A. baumannii (CRAB) a critical priority microorganism requiring urgent attention and the development of new therapeutic options. Here, we screened for prophages in 158 genomes of A. baumannii, comprising 139 complete genomes from the Bacterial and Viral Bioinformatics Resource Center (BV-BRC), and 19 newly sequenced clinical isolates. Additionally, we conducted phylogenetic analyses of prophages, highlighting their diversity and local clustering. The analyzed genomes harbored at least two prophage regions, resulting in the identification of a total of 950 prophage regions, of which 348 were considered complete prophages through software analysis and manual curation, while the remainder may represent prophage remnants. The complete prophages ranged from 28.6 to 103.9 kbp, with an average GC content of 39%. Based on genomic similarity, only 18 complete prophages were taxonomically classified to the genus Vieuvirus. Among all identified complete prophages, we identified 166 genes encoding for putative lysins, while prophage regions that were not considered complete could also harbor putative lysins. These findings highlight the abundance of prophage-encoded lysins in A. baumannii genomes, which are promising therapeutic agents for combating A. baumannii infections, particularly in the face of rising antibiotic resistance.
Insights
Carbapenem-resistant Acinetobacter baumannii (CRAB) is a critical threat. Researchers found numerous prophages in CRAB genomes, many encoding lysins, which are promising new therapies against antibiotic-resistant infections.
Area of Science:
- Microbiology and Virology
- Genomics and Bioinformatics
- Infectious Diseases and Therapeutics
Background:
- Acinetobacter baumannii is a Gram-negative opportunistic pathogen causing global nosocomial infections.
- Increasing antibiotic resistance, particularly carbapenem resistance (CRAB), makes it a critical priority for new treatments.
- Prophages, viral DNA integrated into bacterial genomes, are increasingly recognized for their therapeutic potential.
Purpose of the Study:
- To screen for and characterize prophages within Acinetobacter baumannii genomes.
- To identify prophage-encoded genes, specifically those for putative lysins.
- To evaluate the therapeutic potential of these prophages and their encoded lysins against CRAB.
Main Methods:
- Screened 158 Acinetobacter baumannii genomes (139 complete, 19 clinical isolates) for prophage regions.
- Utilized bioinformatics software and manual curation to identify and analyze complete prophages.
- Conducted phylogenetic analyses to understand prophage diversity and taxonomic classification.
- Identified and quantified genes encoding putative lysins within prophage regions.
Main Results:
- Identified 950 prophage regions, with 348 classified as complete prophages.
- Complete prophages varied in size (28.6–103.9 kbp) with an average GC content of 39%.
- Discovered 166 genes encoding putative lysins within complete prophages, with potential in incomplete regions as well.
- Only 18 complete prophages were taxonomically classified to the genus Vieuvirus.
Conclusions:
- Acinetobacter baumannii genomes are rich in prophage sequences.
- Prophage-encoded lysins represent a significant reservoir of potential therapeutic agents.
- These findings offer promising avenues for developing novel treatments against antibiotic-resistant Acinetobacter baumannii infections.
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