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oai: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

00925njm 22002777a 4500 dc Vázquez, Roberto author Doménech-Sánchez, Antonio author Ruiz, Susana author Sempere, Julio author Yuste, Jose Enrique author Alberti, Sebastian author García, Pedro author 2022-10-21 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. 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 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