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.
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