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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 <jats:italic>in vitro<\/jats:italic> activity of the novel peptide-peptoid hybrid <jats:bold>B1<\/jats:bold> against canine isolates of <jats:italic>S<\/jats:italic>. <jats:italic>pseudintermedius<\/jats:italic> and <jats:italic>P<\/jats:italic>. <jats:italic>aeruginosa<\/jats:italic>. <jats:bold>B1<\/jats:bold> showed potent minimum inhibitory concentrations (MICs) against canine <jats:italic>S<\/jats:italic>. <jats:italic>pseudintermedius<\/jats:italic> and <jats:italic>P<\/jats:italic>. <jats:italic>aeruginosa<\/jats:italic> isolates as well rapid killing kinetics. <jats:bold>B1<\/jats:bold> was found to disrupt the membrane integrity and affect cell-wall synthesis in methicillin-resistant <jats:italic>S<\/jats:italic>. <jats:italic>pseudintermedius<\/jats:italic> (MRSP). We generated 28 analogues of <jats:bold>B1<\/jats:bold>, showing comparable haemolysis and MICs against MRSP and <jats:italic>P<\/jats:italic>. <jats:italic>aeruginosa<\/jats:italic>. The most active analogues (<jats:bold>23<\/jats:bold>, <jats:bold>26<\/jats:bold>) and <jats:bold>B1<\/jats:bold> were tested against a collection of clinical isolates from canine, of which only <jats:bold>B1<\/jats:bold> showed potent activity. Our best compound <jats:bold>26<\/jats:bold>, displayed activity against <jats:italic>P<\/jats:italic>. <jats:italic>aeruginosa<\/jats:italic> and <jats:italic>S<\/jats:italic>. <jats:italic>pseudintermedius<\/jats:italic>, but not the closely related <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic>. This work shows that design of target-specific veterinary antimicrobial agents is possible, even species within a genus, and deserves further exploration.<\/jats:p>","DOI":"10.1038\/s41598-019-39042-3","type":"journal-article","created":{"date-parts":[[2019,3,6]],"date-time":"2019-03-06T11:07:05Z","timestamp":1551870425000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Characterization, mechanism of action and optimization of activity of a novel peptide-peptoid hybrid against bacterial pathogens involved in canine skin infections"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2348-3688","authenticated-orcid":false,"given":"Ines","family":"Greco","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnete Plahn","family":"Emborg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bimal","family":"Jana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Molchanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Oddo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Damborg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Guardabassi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9357-8001","authenticated-orcid":false,"given":"Paul R.","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,3,6]]},"reference":[{"key":"39042_CR1","doi-asserted-by":"crossref","unstructured":"Peacock, S. 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