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PlyKp104, a Novel Phage Lysin for the Treatment of Klebsiella pneumoniae, Pseudomonas aeruginosa, and Other Gram-Negative ESKAPE Pathogens

Euler, Chad W. ; Raz, Assaf ; Hernandez, Anaise ; Serrano, Anna ; Xu, Siyue ; Andersson, Martin LU ; Zou, Geng ; Zhang, Yue ; Fischetti, Vincent A. and Li, Jinquan (2023) In Antimicrobial Agents and Chemotherapy 67(5).
Abstract

Klebsiella pneumoniae and Pseudomonas aeruginosa are two leading causes of burn and wound infections, pneumonia, urinary tract infections, and more severe invasive diseases, which are often multidrug resistant (MDR) or extensively drug resistant. Due to this, it is critical to discover alternative antimicrobials, such as bacteriophage lysins, against these pathogens. Unfortunately, most lysins that target Gram-negative bacteria require additional modifications or outer membrane permeabilizing agents to be bactericidal. We identified four putative lysins through bioinformatic analysis of Pseudomonas and Klebsiella phage genomes in the NCBI database and then expressed and tested their intrinsic lytic activity in vitro. The most active... (More)

Klebsiella pneumoniae and Pseudomonas aeruginosa are two leading causes of burn and wound infections, pneumonia, urinary tract infections, and more severe invasive diseases, which are often multidrug resistant (MDR) or extensively drug resistant. Due to this, it is critical to discover alternative antimicrobials, such as bacteriophage lysins, against these pathogens. Unfortunately, most lysins that target Gram-negative bacteria require additional modifications or outer membrane permeabilizing agents to be bactericidal. We identified four putative lysins through bioinformatic analysis of Pseudomonas and Klebsiella phage genomes in the NCBI database and then expressed and tested their intrinsic lytic activity in vitro. The most active lysin, PlyKp104, exhibited .5-log killing against K. pneumoniae, P. aeruginosa, and other Gram-negative representatives of the multidrug-resistant ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, K. pneumonia, Acinetobacter baumannii, P. aeruginosa, and Enterobacter species) without further modification. PlyKp104 displayed rapid killing and high activity over a wide pH range and in high concentrations of salt and urea. Additionally, pulmonary surfactants and low concentrations of human serum did not inhibit PlyKp104 activity in vitro. PlyKp104 also significantly reduced drug-resistant K. pneumoniae .2 logs in a murine skin infection model after one treatment of the wound, suggesting that this lysin could be used as a topical antimicrobial against K. pneumoniae and other MDR Gram-negative infections.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
antibiotic resistance, bacteriophage, endolysin, ESKAPE, Gram negative, Klebsiella, lysin, Pseudomonas, skin infection
in
Antimicrobial Agents and Chemotherapy
volume
67
issue
5
publisher
American Society for Microbiology
external identifiers
  • pmid:37098944
  • scopus:85159770387
ISSN
0066-4804
DOI
10.1128/aac.01519-22
language
English
LU publication?
yes
id
66ee657d-19fb-4efa-b90b-ca176f803d8b
date added to LUP
2023-08-22 10:19:07
date last changed
2025-05-04 11:53:48
@article{66ee657d-19fb-4efa-b90b-ca176f803d8b,
  abstract     = {{<p>Klebsiella pneumoniae and Pseudomonas aeruginosa are two leading causes of burn and wound infections, pneumonia, urinary tract infections, and more severe invasive diseases, which are often multidrug resistant (MDR) or extensively drug resistant. Due to this, it is critical to discover alternative antimicrobials, such as bacteriophage lysins, against these pathogens. Unfortunately, most lysins that target Gram-negative bacteria require additional modifications or outer membrane permeabilizing agents to be bactericidal. We identified four putative lysins through bioinformatic analysis of Pseudomonas and Klebsiella phage genomes in the NCBI database and then expressed and tested their intrinsic lytic activity in vitro. The most active lysin, PlyKp104, exhibited .5-log killing against K. pneumoniae, P. aeruginosa, and other Gram-negative representatives of the multidrug-resistant ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, K. pneumonia, Acinetobacter baumannii, P. aeruginosa, and Enterobacter species) without further modification. PlyKp104 displayed rapid killing and high activity over a wide pH range and in high concentrations of salt and urea. Additionally, pulmonary surfactants and low concentrations of human serum did not inhibit PlyKp104 activity in vitro. PlyKp104 also significantly reduced drug-resistant K. pneumoniae .2 logs in a murine skin infection model after one treatment of the wound, suggesting that this lysin could be used as a topical antimicrobial against K. pneumoniae and other MDR Gram-negative infections.</p>}},
  author       = {{Euler, Chad W. and Raz, Assaf and Hernandez, Anaise and Serrano, Anna and Xu, Siyue and Andersson, Martin and Zou, Geng and Zhang, Yue and Fischetti, Vincent A. and Li, Jinquan}},
  issn         = {{0066-4804}},
  keywords     = {{antibiotic resistance; bacteriophage; endolysin; ESKAPE; Gram negative; Klebsiella; lysin; Pseudomonas; skin infection}},
  language     = {{eng}},
  number       = {{5}},
  publisher    = {{American Society for Microbiology}},
  series       = {{Antimicrobial Agents and Chemotherapy}},
  title        = {{PlyKp104, a Novel Phage Lysin for the Treatment of Klebsiella pneumoniae, Pseudomonas aeruginosa, and Other Gram-Negative ESKAPE Pathogens}},
  url          = {{http://dx.doi.org/10.1128/aac.01519-22}},
  doi          = {{10.1128/aac.01519-22}},
  volume       = {{67}},
  year         = {{2023}},
}