Activity of AMP2041 against human and animal multidrug resistant Pseudomonas aeruginosa clinical isolates

Annals of Clinical Microbiology and Antimicrobials

Research

Edoardo Carretto¹  Giovanni Ghibaudo²  Andrea Sala³  Davide Santospirito³  Simone Taddei³  Clotilde Silvia Cabassi³  Giovanni Loris Alborali⁴ 

[1] Arcispedale S. Maria Nuova, Viale Risorgimento 80, 42123, Reggio Emilia, Italy;Clinica Veterinaria Malpensa, Via Marconi 27, 21017, Samarate, VA, Italy;Department of Veterinary Science, University of Parma, Via del Taglio 10, 43126, Parma, Italy;Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna, Via Bianchi 7/9, 25124, Brescia, Italy;

关键词: Antimicrobial peptide;    Pseudomonas aeruginosa;    Cinical isolates;    Multidrug resistance;    Bacterial membrane damage;   

DOI  :  10.1186/s12941-017-0193-1

 received in 2016-07-21, accepted in 2017-03-18,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundAntimicrobial resistance is a growing threat to public health. Pseudomonas aeruginosa is a relevant pathogen causing human and animal infections, frequently displaying high levels of resistance to commonly used antimicrobials. The increasing difficulty to develop new effective antibiotics have discouraged investment in this area and only a few new antibiotics are currently under development. An approach to overcome antibiotic resistance could be based on antimicrobial peptides since they offer advantages over currently used microbicides.MethodsThe antimicrobial activity of the synthetic peptide AMP2041 was evaluated against 49 P. aeruginosa clinical strains with high levels of antimicrobial resistance, isolated from humans (n = 19) and animals (n = 30). In vitro activity was evaluated by a microdilution assay for lethal dose 90% (LD90), while the activity over time was performed by time-kill assay with 12.5 µg/ml of AMP2014. Evidences for a direct membrane damage were investigated on P. aeruginosa ATCC 27853 reference strain, on animal isolate PA-VET 38 and on human isolate PA-H 24 by propidium iodide and on P. aeruginosa ATCC 27853 by scanning electron microscopy.ResultsAMP2041 showed a dose-dependent activity, with a mean (SEM) LD90 of 1.69 and 3.3 µg/ml for animal and human strains, respectively. AMP2041 showed microbicidal activity on P. aeruginosa isolates from a patient with cystic fibrosis (CF) and resistance increased from first infection isolate (LD90 = 0.3 μg/ml) to the mucoid phenotype (LD90 = 10.4 μg/ml). The time-kill assay showed a time-dependent bactericidal effect of AMP2041 and LD90 was reached within 20 min for all the strains. The stain-dead assay showed an increasing of membrane permeabilization and SEM analysis revealed holes, dents and bursts throughout bacterial cell wall after 30 min of incubation with AMP2041.ConclusionsThe obtained results assessed for the first time the good antimicrobial activity of AMP2041 on P. aeruginosa strains of human origin, including those deriving from a CF patient. We confirmed the excellent antimicrobial activity of AMP2041 on P. aeruginosa strains derived from dog otitis. We also assessed that AMP2041 antimicrobial activity is linked to changes of the P. aeruginosa cell wall morphology and to the increasing of membrane permeability.

【 授权许可】

CC BY   
© The Author(s) 2017