Antiseptic 9-Meric Peptide with Potency against Carbapenem-Resistant Acinetobacter baumannii Infection
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Krishnan, Manigandan | - |
dc.contributor.author | Choi, Joonhyeok | - |
dc.contributor.author | Jang, Ahjin | - |
dc.contributor.author | Yoon, Young Kyung | - |
dc.contributor.author | Kim, Yangmee | - |
dc.date.accessioned | 2022-04-18T20:42:03Z | - |
dc.date.available | 2022-04-18T20:42:03Z | - |
dc.date.created | 2022-04-18 | - |
dc.date.issued | 2021-11 | - |
dc.identifier.issn | 1661-6596 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/140336 | - |
dc.description.abstract | Carbapenem-resistant A. baumannii (CRAB) infection can cause acute host reactions that lead to high-fatality sepsis, making it important to develop new therapeutic options. Previously, we developed a short 9-meric peptide, Pro9-3D, with significant antibacterial and cytotoxic effects. In this study, we attempted to produce safer peptide antibiotics against CRAB by reversing the parent sequence to generate R-Pro9-3 and R-Pro9-3D. Among the tested peptides, R-Pro9-3D had the most rapid and effective antibacterial activity against Gram-negative bacteria, particularly clinical CRAB isolates. Analyses of antimicrobial mechanisms based on lipopolysaccharide (LPS)-neutralization, LPS binding, and membrane depolarization, as well as SEM ultrastructural investigations, revealed that R-Pro9-3D binds strongly to LPS and impairs the membrane integrity of CRAB by effectively permeabilizing its outer membrane. R-Pro9-3D was also less cytotoxic and had better proteolytic stability than Pro9-3D and killed biofilm forming CRAB. As an LPS-neutralizing peptide, R-Pro9-3D effectively reduced LPS-induced pro-inflammatory cytokine levels in RAW 264.7 cells. The antiseptic abilities of R-Pro9-3D were also investigated using a mouse model of CRAB-induced sepsis, which revealed that R-Pro9-3D reduced multiple organ damage and attenuated systemic infection by acting as an antibacterial and immunosuppressive agent. Thus, R-Pro9-3D displays potential as a novel antiseptic peptide for treating Gram-negative CRAB infections. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | MDPI | - |
dc.subject | ANTIMICROBIAL PEPTIDES | - |
dc.subject | ANTIBIOTIC-RESISTANCE | - |
dc.subject | BIOFILM FORMATION | - |
dc.subject | ANALOGS | - |
dc.subject | LIPOPOLYSACCHARIDE | - |
dc.subject | MECHANISMS | - |
dc.subject | PEPTIDOMIMETICS | - |
dc.subject | PROTAETIAMYCINE | - |
dc.subject | COMBINATIONS | - |
dc.subject | COLISTIN | - |
dc.title | Antiseptic 9-Meric Peptide with Potency against Carbapenem-Resistant Acinetobacter baumannii Infection | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Yoon, Young Kyung | - |
dc.identifier.doi | 10.3390/ijms222212520 | - |
dc.identifier.scopusid | 2-s2.0-85119260823 | - |
dc.identifier.wosid | 000728576800001 | - |
dc.identifier.bibliographicCitation | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.22, no.22 | - |
dc.relation.isPartOf | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | - |
dc.citation.title | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | - |
dc.citation.volume | 22 | - |
dc.citation.number | 22 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Multidisciplinary | - |
dc.subject.keywordPlus | ANTIMICROBIAL PEPTIDES | - |
dc.subject.keywordPlus | ANTIBIOTIC-RESISTANCE | - |
dc.subject.keywordPlus | BIOFILM FORMATION | - |
dc.subject.keywordPlus | ANALOGS | - |
dc.subject.keywordPlus | LIPOPOLYSACCHARIDE | - |
dc.subject.keywordPlus | MECHANISMS | - |
dc.subject.keywordPlus | PEPTIDOMIMETICS | - |
dc.subject.keywordPlus | PROTAETIAMYCINE | - |
dc.subject.keywordPlus | COMBINATIONS | - |
dc.subject.keywordPlus | COLISTIN | - |
dc.subject.keywordAuthor | antimicrobial peptide | - |
dc.subject.keywordAuthor | < | - |
dc.subject.keywordAuthor | p> | - |
dc.subject.keywordAuthor | A. baumannii< | - |
dc.subject.keywordAuthor | /p> | - |
dc.subject.keywordAuthor | null | - |
dc.subject.keywordAuthor | carbapenem-resistance | - |
dc.subject.keywordAuthor | sepsis | - |
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