Inovirus-Encoded Peptides Induce Specific Toxicity in Pseudomonas aeruginosa
Juehua Weng1,2, Yunxue Guo1,2, Jiayu Gu1,2
1Key Laboratory of Tropical Marine Bio-resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 511458, China.
Abstract:
Pseudomonas aeruginosa 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 P. aeruginosa 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 (zot 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 P. aeruginosa, 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 P. aeruginosa among the tested bacterial strains. Our study reveals that the novel Pf-encoded polypeptide PftP4 has the potential to selectively target and eradicate P. aeruginosa, offering valuable insights for combating P. aeruginosa infections.
Insights
A novel protein, Pf4-encoded toxic polypeptide (PftP4), derived from Pseudomonas aeruginosa phages, selectively kills bacteria. This discovery offers a new strategy against dangerous, antibiotic-resistant Pseudomonas aeruginosa infections.
Area of Science:
- Bacteriology
- Virology
- Molecular Biology
Background:
- Pseudomonas aeruginosa is a significant opportunistic pathogen causing hospital-acquired infections.
- Antibiotic resistance in P. aeruginosa necessitates alternative therapeutic strategies.
- Filamentous phages (Pfs) in P. aeruginosa can impede phage therapy efficacy due to defense genes.
Purpose of the Study:
- To identify and characterize novel antimicrobial agents from P. aeruginosa phages.
- To investigate the potential of phage-encoded proteins as therapeutic agents against P. aeruginosa.
Main Methods:
- Genomic analysis of the Pf4 prophage to identify novel genes.
- Gene cloning and protein overexpression to study PftP4 function.
- Bacterial toxicity assays and subcellular localization studies.
Main Results:
- A new 33-amino-acid polypeptide, PftP4, was identified from the Pf4 prophage.
- PftP4 exhibits toxicity towards P. aeruginosa by increasing cell membrane permeability.
- Homologues of PftP4 are present in other Pf phages and show specific toxicity against P. aeruginosa.
Conclusions:
- The novel PftP4 polypeptide selectively targets and eradicates P. aeruginosa.
- PftP4 represents a promising candidate for developing new treatments against P. aeruginosa infections.
- Understanding PftP4 function provides insights into phage-bacteria interactions and potential therapeutic applications.
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