Antibacterial Activity of Novel Cationic Peptides against Clinical Isolates of Multi-Drug Resistant Staphylococcus pseudintermedius from Infected Dogs

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dc.contributor.authorMohamed, Mohamed F.en
dc.contributor.authorHammac, G. Kenitraen
dc.contributor.authorGuptill, Lynnen
dc.contributor.authorSeleem, Mohamed N.en
dc.date.accessioned2020-09-21T16:09:35Zen
dc.date.available2020-09-21T16:09:35Zen
dc.date.issued2014-12-31en
dc.date.updated2020-09-21T16:09:30Zen
dc.description.abstractStaphylococcus pseudintermedius is a major cause of skin and soft tissue infections in companion animals and has zoonotic potential. Additionally, methicillin-resistant S. pseudintermedius (MRSP) has emerged with resistance to virtually all classes of antimicrobials. Thus, novel treatment options with new modes of action are required. Here, we investigated the antimicrobial activity of six synthetic short peptides against clinical isolates of methicillin-susceptible and MRSP isolated from infected dogs. All six peptides demonstrated potent anti-staphylococcal activity regardless of existing resistance phenotype. The most effective peptides were RRIKA (with modified C terminus to increase amphipathicity and hydrophobicity) and WR-12 (α-helical peptide consisting exclusively of arginine and tryptophan) with minimum inhibitory concentration50 (MIC50) of 1 µM and MIC90 of 2 µM. RR (short anti-inflammatory peptide) and IK8 "D isoform" demonstrated good antimicrobial activity with MIC50 of 4 µM and MIC90 of 8 µM. Penetratin and (KFF)3K (two cell penetrating peptides) were the least effective with MIC50 of 8 µM and MIC90 of 16 µM. Killing kinetics revealed a major advantage of peptides over conventional antibiotics, demonstrating potent bactericidal activity within minutes. Studies with propidium iodide and transmission electron microscopy revealed that peptides damaged the bacterial membrane leading to leakage of cytoplasmic contents and consequently, cell death. A potent synergistic increase in the antibacterial effect of the cell penetrating peptide (KFF)3K was noticed when combined with other peptides and with antibiotics. In addition, all peptides displayed synergistic interactions when combined together. Furthermore, peptides demonstrated good therapeutic indices with minimal toxicity toward mammalian cells. Resistance to peptides did not evolve after 10 passages of S. pseudintermedius at sub-inhibitory concentration. However, the MICs of amikacin and ciprofloxacin increased 32 and 8 fold, respectively; under similar conditions. Taken together, these results support designing of peptide-based therapeutics for combating MRSP infections, particularly for topical application.en
dc.description.versionPublished versionen
dc.format.extent20 page(s)en
dc.format.mediumElectronic-eCollectionen
dc.format.mimetypeapplication/pdfen
dc.identifierARTN e116259 (Article number)en
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0116259en
dc.identifier.eissn1932-6203en
dc.identifier.issn1932-6203en
dc.identifier.issue12en
dc.identifier.orcidSeleem, Mohamed [0000-0003-0939-0458]en
dc.identifier.otherPONE-D-14-27838 (PII)en
dc.identifier.pmid25551573 (pubmed)en
dc.identifier.urihttp://hdl.handle.net/10919/100017en
dc.identifier.volume9en
dc.language.isoenen
dc.publisherPLoSen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectCELL-PENETRATING PEPTIDESen
dc.subjectANTIMICROBIAL PEPTIDESen
dc.subjectPSEUDOMONAS-AERUGINOSAen
dc.subjectBACTERIAen
dc.subjectAUREUSen
dc.subjectMEMBRANEen
dc.subjectMECHANISMSen
dc.subjectSEQUENCEen
dc.subjectDESIGNen
dc.subject.meshCells, Cultureden
dc.subject.meshKeratinocytesen
dc.subject.meshAnimalsen
dc.subject.meshDogsen
dc.subject.meshHumansen
dc.subject.meshStaphylococcusen
dc.subject.meshStaphylococcal Infectionsen
dc.subject.meshDog Diseasesen
dc.subject.meshAntimicrobial Cationic Peptidesen
dc.subject.meshAnti-Bacterial Agentsen
dc.subject.meshMicrobial Sensitivity Testsen
dc.subject.meshDrug Resistance, Multiple, Bacterialen
dc.subject.meshCell Membrane Permeabilityen
dc.subject.meshAmino Acid Sequenceen
dc.subject.meshStructure-Activity Relationshipen
dc.subject.meshMolecular Sequence Dataen
dc.subject.meshMethicillin-Resistant Staphylococcus aureusen
dc.titleAntibacterial Activity of Novel Cationic Peptides against Clinical Isolates of Multi-Drug Resistant Staphylococcus pseudintermedius from Infected Dogsen
dc.title.serialPLOS ONEen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2014-12-04en
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Biomedical Sciences and Pathobiologyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/CVM T&R Facultyen
pubs.organisational-group/Virginia Techen

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