Mechanism of action and in vitro activity of short hybrid antimicrobial peptide PV3 against Pseudomonas aeruginosa

2016 ◽  
Vol 479 (1) ◽  
pp. 103-108 ◽  
Author(s):  
Hamed Memariani ◽  
Delavar Shahbazzadeh ◽  
Jean-Marc Sabatier ◽  
Mojtaba Memariani ◽  
Ali Karbalaeimahdi ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Peptide ◽  
Mechanism Of Action ◽  
Vitro Activity ◽  
In Vitro Activity

Murepavadin antimicrobial activity against and resistance development in cystic fibrosis Pseudomonas aeruginosa isolates

2020 ◽  
Author(s):  
María Díez-Aguilar ◽  
Marta Hernández-García ◽  
María-Isabel Morosini ◽  
Ad Fluit ◽  
Michael M Tunney ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Spontaneous Mutation ◽  
Lung Surfactant ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Agar Dilution

Abstract Background Murepavadin, a novel peptidomimetic antibiotic, is being developed as an inhalation therapy for treatment of Pseudomonas aeruginosa respiratory infection in people with cystic fibrosis (CF). It blocks the activity of the LptD protein in P. aeruginosa causing outer membrane alterations. Objectives To determine the in vitro activity of murepavadin against CF P. aeruginosa isolates and to investigate potential mechanisms of resistance. Methods MIC values were determined by both broth microdilution and agar dilution and results compared. The effect of artificial sputum and lung surfactant on in vitro activity was also measured. Spontaneous mutation frequency was estimated. Bactericidal activity was investigated using time–kill assays. Resistant mutants were studied by WGS. Results The murepavadin MIC50 was 0.125 versus 4 mg/L and the MIC90 was 2 versus 32 mg/L by broth microdilution and agar dilution, respectively. Essential agreement was >90% when determining in vitro activity with artificial sputum or lung surfactant. It was bactericidal at a concentration of 32 mg/L against 95.4% of the strains within 1–5 h. Murepavadin MICs were 2–9 two-fold dilutions higher for the mutant derivatives (0.5 to >16 mg/L) than for the parental strains. Second-step mutants were obtained for the PAO mutS reference strain with an 8×MIC increase. WGS showed mutations in genes involved in LPS biosynthesis (lpxL1, lpxL2, bamA2, lptD, lpxT and msbA). Conclusions Murepavadin characteristics, such as its specific activity against P. aeruginosa, its unique mechanism of action and its strong antimicrobial activity, encourage the further clinical evaluation of this drug.

In vitro Activity of Ceftriaxone and Amikacin against Pseudomonas aeruginosa

Chemotherapy ◽  
1991 ◽  
Vol 37 (2) ◽  
pp. 93-97 ◽  
Author(s):  
Barbara La T. Prosser ◽  
Doris B. Taylor ◽  
Roy Cleeland
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Vitro Activity ◽  
In Vitro Activity
Sign in / Sign up

Export Citation Format

Share Document