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1.
Sci Rep ; 9(1): 8361, 2019 Jun 04.
Article in English | MEDLINE | ID: mdl-31164676

ABSTRACT

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

2.
Sci Rep ; 9(1): 3679, 2019 03 06.
Article in English | MEDLINE | ID: mdl-30842436

ABSTRACT

Integumentary infections like pyoderma represent the main reason for antimicrobial prescription in dogs. Staphylococcus pseudintermedius and Pseudomonas aeruginosa are frequently identified in these infections, and both bacteria are challenging to combat due to resistance. To avoid use of important human antibiotics for treatment of animal infections there is a pressing need for novel narrow-spectrum antimicrobial agents in veterinary medicine. Herein, we characterize the in vitro activity of the novel peptide-peptoid hybrid B1 against canine isolates of S. pseudintermedius and P. aeruginosa. B1 showed potent minimum inhibitory concentrations (MICs) against canine S. pseudintermedius and P. aeruginosa isolates as well rapid killing kinetics. B1 was found to disrupt the membrane integrity and affect cell-wall synthesis in methicillin-resistant S. pseudintermedius (MRSP). We generated 28 analogues of B1, showing comparable haemolysis and MICs against MRSP and P. aeruginosa. The most active analogues (23, 26) and B1 were tested against a collection of clinical isolates from canine, of which only B1 showed potent activity. Our best compound 26, displayed activity against P. aeruginosa and S. pseudintermedius, but not the closely related S. aureus. This work shows that design of target-specific veterinary antimicrobial agents is possible, even species within a genus, and deserves further exploration.


Subject(s)
Anti-Bacterial Agents/pharmacology , Dog Diseases/microbiology , Pseudomonas aeruginosa/drug effects , Skin Diseases, Bacterial/microbiology , Skin Diseases, Bacterial/veterinary , Staphylococcus/drug effects , Animals , Anti-Bacterial Agents/chemistry , Dogs , Microbial Sensitivity Tests , Peptides/chemistry , Peptides/pharmacology , Peptoids/chemistry , Peptoids/pharmacology , Pseudomonas Infections/microbiology , Pseudomonas Infections/veterinary , Pseudomonas aeruginosa/pathogenicity , Staphylococcal Skin Infections/microbiology , Staphylococcal Skin Infections/veterinary , Staphylococcus/pathogenicity , Structure-Activity Relationship
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