Inovirus-Encoded Peptides Induce Specific Toxicity in <i>Pseudomonas aeruginosa</i>

<i>Pseudomonas aeruginosa</i> is a common opportunistic pathogen associated with nosocomial infections. The primary treatment for infections typically involves antibiotics, which can lead to the emergence of multidrug-resistant strains. Therefore, there is a pressing need for safe and ef...

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Bibliographic Details
Main Authors: Juehua Weng, Yunxue Guo, Jiayu Gu, Ran Chen, Xiaoxue Wang
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/17/1/112
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Summary:<i>Pseudomonas aeruginosa</i> is a common opportunistic pathogen associated with nosocomial infections. The primary treatment for infections typically involves antibiotics, which can lead to the emergence of multidrug-resistant strains. Therefore, there is a pressing need for safe and effective alternative methods. Phage therapy stands out as a promising approach. However, filamentous prophages (Pfs) commonly found in <i>P. aeruginosa</i> encode genes with phage defense activity, thereby reducing the efficacy of phage therapy. Through a genomic analysis of the Pf4 prophage, we identified a 102 bp gene co-transcribed with the upstream gene responsible for phage release (<i>zot</i> gene), giving rise to a 33-amino-acid polypeptide that we have named Pf4-encoded toxic polypeptide (PftP4). The overexpression of PftP4 demonstrated cellular toxicity in <i>P. aeruginosa</i>, with subcellular localization indicating its presence in the cell membrane and a subsequent increase in membrane permeability. Notably, PftP4 homologues are found in multiple Pf phages and exhibit specificity in their toxicity towards <i>P. aeruginosa</i> among the tested bacterial strains. Our study reveals that the novel Pf-encoded polypeptide PftP4 has the potential to selectively target and eradicate <i>P. aeruginosa</i>, offering valuable insights for combating <i>P. aeruginosa</i> infections.
ISSN:1999-4915