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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.

scientific reports

Characterization, mechanism of action and optimization of activity of a novel peptide-peptoid hybrid against bacterial pathogens involved in canine skin infections