2026-07-22T20:05:48Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/159772025-03-20T10:55:42Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19609col_20.500.12105_16967
Repisalud
author
Vázquez, Roberto
author
Doménech-Sánchez, Antonio
author
Ruiz, Susana
author
Sempere, Julio
author
Yuste, Jose Enrique
author
Alberti, Sebastian
author
García, Pedro
funder
Ministerio de Economía y Competitividad (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Centro de Investigación Biomédica en Red - CIBERES (Enfermedades Respiratorias)
funder
Instituto de Salud Carlos III
2023-05-05T07:36:44Z
2023-05-05T07:36:44Z
2022-10-21
Antibiotics (Basel). 2022 Oct 21;11(10):1448.
10.3390/antibiotics11101448
2079-6382
Antibiotics (Basel, Switzerland)
http://hdl.handle.net/20.500.13003/18202
36290106
L2019740193
2-s2.0-85140467040
http://hdl.handle.net/20.500.12105/15977
872018200001
Phage lysins are a promising alternative to common antibiotic chemotherapy. However, they have been regarded as less effective against Gram-negative pathogens unless engineered, e.g., by fusing them to antimicrobial peptides (AMPs). AMPs themselves pose an alternative to antibiotics. In this work, AMP P87, previously derived from a phage lysin (Pae87) with a presumed nonenzymatic mode-of-action, was investigated to improve its antibacterial activity. Five modifications were designed to maximize the hydrophobic moment and net charge, producing the modified peptide P88, which was evaluated in terms of bactericidal activity, cytotoxicity, MICs or synergy with antibiotics. P88 had a better bactericidal performance than P87 (an average of 6.0 vs. 1.5 log-killing activity on Pseudomonas aeruginosa strains treated with 10 µM). This did not correlate with a dramatic increase in cytotoxicity as assayed on A549 cell cultures. P88 was active against a range of P. aeruginosa isolates, with no intrinsic resistance factors identified. Synergy with some antibiotics was observed in vitro, in complex media, and in a respiratory infection mouse model. Therefore, P88 can be a new addition to the therapeutic toolbox of alternative antimicrobials against Gram-negative pathogens as a sole therapeutic, a complement to antibiotics, or a part to engineer proteinaceous antimicrobials.
eng
Phage lysins
Antimicrobial peptides
Pseudomonas aeruginosa
Synergy
Improvement of the Antibacterial Activity of Phage Lysin-Derived Peptide P87 through Maximization of Physicochemical Properties and Assessment of Its Therapeutic Potential
research article
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https://repisalud.isciii.es/bitstreams/f2ce1f06-06ee-4aa2-98d1-28a6eee692a7/download
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ImprovementAntibacterialActivityPhage_2022.pdf
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https://repisalud.isciii.es/bitstreams/260bd5f9-2015-4644-8c15-38db9f0d5142/download
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text/plain
ImprovementAntibacterialActivityPhage_2022.pdf.txt