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Antibacterial and Antifungal Properties of a Novel Antimicrobial Peptide GK-19 and Its Application in Skin and Soft Tissue Infections Induced by MRSA or Candida albicans
The increasing resistance of human pathogens promotes the development of novel antimicrobial agents. Due to the physical bactericidal mechanism of membrane disruption, antimicrobial peptides are considered as potential therapeutic candidates without inducing microbial resistance. Scorpion venom-deri...
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Published in: | Pharmaceutics 2022-09, Vol.14 (9), p.1937 |
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description | The increasing resistance of human pathogens promotes the development of novel antimicrobial agents. Due to the physical bactericidal mechanism of membrane disruption, antimicrobial peptides are considered as potential therapeutic candidates without inducing microbial resistance. Scorpion venom-derived peptide, Androctonus amoreuxi Antimicrobial Peptide 1 (AamAP1), has been proved to have broad-spectrum antimicrobial properties. However, AamAP1 can induce hemolysis and shows strong toxicity against mammalian cells. Herein, the antimicrobial activity and mechanism of a novel synthetic antimicrobial peptide, GK-19, derived from AamAP1 and its derivatives, was evaluated. Five bacteria and three fungi were used to evaluate the antimicrobial effects of GK-19 in vitro. Scalded mice models combined with skin and soft tissue infections (SSTIs) were used to evaluate its applicability. The results indicated that GK-19 could not only inhibit Gram-positive and Gram-negative bacterial growth, but also kill fungi by disrupting the microbial cell membrane. Meanwhile, GK-19 showed negligible toxicity to mammalian cells, low hemolytic activity and high stability in plasma. Furthermore, in scalded mice models combined with SSTIs induced by either Methicillin-Resistant Staphylococcus aureus (MRSA) or Candida albicans, GK-19 showed significant antimicrobial and healing effects. Overall, it was demonstrated that GK-19 might be a promising drug candidate in the battle against drug-resistant bacterial and fungal infections. |
doi_str_mv | 10.3390/pharmaceutics14091937 |
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Due to the physical bactericidal mechanism of membrane disruption, antimicrobial peptides are considered as potential therapeutic candidates without inducing microbial resistance. Scorpion venom-derived peptide, Androctonus amoreuxi Antimicrobial Peptide 1 (AamAP1), has been proved to have broad-spectrum antimicrobial properties. However, AamAP1 can induce hemolysis and shows strong toxicity against mammalian cells. Herein, the antimicrobial activity and mechanism of a novel synthetic antimicrobial peptide, GK-19, derived from AamAP1 and its derivatives, was evaluated. Five bacteria and three fungi were used to evaluate the antimicrobial effects of GK-19 in vitro. Scalded mice models combined with skin and soft tissue infections (SSTIs) were used to evaluate its applicability. The results indicated that GK-19 could not only inhibit Gram-positive and Gram-negative bacterial growth, but also kill fungi by disrupting the microbial cell membrane. Meanwhile, GK-19 showed negligible toxicity to mammalian cells, low hemolytic activity and high stability in plasma. Furthermore, in scalded mice models combined with SSTIs induced by either Methicillin-Resistant Staphylococcus aureus (MRSA) or Candida albicans, GK-19 showed significant antimicrobial and healing effects. Overall, it was demonstrated that GK-19 might be a promising drug candidate in the battle against drug-resistant bacterial and fungal infections.</description><identifier>ISSN: 1999-4923</identifier><identifier>EISSN: 1999-4923</identifier><identifier>DOI: 10.3390/pharmaceutics14091937</identifier><identifier>PMID: 36145681</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Antibiotics ; Antimicrobial agents ; antimicrobial peptides ; Bacteria ; Candida albicans ; Drug resistance ; Fungi ; GK-19 ; Gram-positive bacteria ; Life sciences ; MRSA ; Nosocomial infections ; Peptides ; Pulmonary arteries ; Scanning electron microscopy ; skin and soft tissue infections ; Staphylococcus infections</subject><ispartof>Pharmaceutics, 2022-09, Vol.14 (9), p.1937</ispartof><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 by the authors. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c482t-9ecad72dc21ae42237fbc048ce668da30321fe204f1cda81402603bd5436bd703</citedby><cites>FETCH-LOGICAL-c482t-9ecad72dc21ae42237fbc048ce668da30321fe204f1cda81402603bd5436bd703</cites><orcidid>0000-0003-3746-9489 ; 0000-0002-1107-7965</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2716585227/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2716585227?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids></links><search><creatorcontrib>Song, Chenghua</creatorcontrib><creatorcontrib>Wen, Ruichao</creatorcontrib><creatorcontrib>Zhou, Jiaxuan</creatorcontrib><creatorcontrib>Zeng, Xiaoyan</creatorcontrib><creatorcontrib>Kou, Zi</creatorcontrib><creatorcontrib>Zhang, Jia</creatorcontrib><creatorcontrib>Wang, Tao</creatorcontrib><creatorcontrib>Chang, Pengkang</creatorcontrib><creatorcontrib>Lv, Yi</creatorcontrib><creatorcontrib>Wu, Rongqian</creatorcontrib><title>Antibacterial and Antifungal Properties of a Novel Antimicrobial Peptide GK-19 and Its Application in Skin and Soft Tissue Infections Induced by MRSA or Candida albicans</title><title>Pharmaceutics</title><description>The increasing resistance of human pathogens promotes the development of novel antimicrobial agents. Due to the physical bactericidal mechanism of membrane disruption, antimicrobial peptides are considered as potential therapeutic candidates without inducing microbial resistance. Scorpion venom-derived peptide, Androctonus amoreuxi Antimicrobial Peptide 1 (AamAP1), has been proved to have broad-spectrum antimicrobial properties. However, AamAP1 can induce hemolysis and shows strong toxicity against mammalian cells. Herein, the antimicrobial activity and mechanism of a novel synthetic antimicrobial peptide, GK-19, derived from AamAP1 and its derivatives, was evaluated. Five bacteria and three fungi were used to evaluate the antimicrobial effects of GK-19 in vitro. Scalded mice models combined with skin and soft tissue infections (SSTIs) were used to evaluate its applicability. The results indicated that GK-19 could not only inhibit Gram-positive and Gram-negative bacterial growth, but also kill fungi by disrupting the microbial cell membrane. Meanwhile, GK-19 showed negligible toxicity to mammalian cells, low hemolytic activity and high stability in plasma. Furthermore, in scalded mice models combined with SSTIs induced by either Methicillin-Resistant Staphylococcus aureus (MRSA) or Candida albicans, GK-19 showed significant antimicrobial and healing effects. Overall, it was demonstrated that GK-19 might be a promising drug candidate in the battle against drug-resistant bacterial and fungal infections.</description><subject>Antibiotics</subject><subject>Antimicrobial agents</subject><subject>antimicrobial peptides</subject><subject>Bacteria</subject><subject>Candida albicans</subject><subject>Drug resistance</subject><subject>Fungi</subject><subject>GK-19</subject><subject>Gram-positive bacteria</subject><subject>Life sciences</subject><subject>MRSA</subject><subject>Nosocomial infections</subject><subject>Peptides</subject><subject>Pulmonary arteries</subject><subject>Scanning electron microscopy</subject><subject>skin and soft tissue infections</subject><subject>Staphylococcus infections</subject><issn>1999-4923</issn><issn>1999-4923</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptks9uEzEQxlcIRKvQR0CyxIVLYP1n1_YFKYqgRBSoSDmvvPY4ddjYi-2t1EfiLfEmFaIIH-zxzM-frG-mql7i-g2lsn473qp4UBqm7HTCrJZYUv6kOsdSyiWThD79Kz6rLlLa12VRigWVz6sz2mLWtAKfV79WPrte6QzRqQEpb9CcsZPflet1DCPE7CChYJFCX8IdDEfg4HQM_fzkGsbsDKDLT0ssjwKbnNBqHAenVXbBI-fR9kfZ5to22IxuXEoToI23oGcildBMGgzq79Hnb9sVChGtC-6MQmroi5BPL6pnVg0JLh7ORfX9w_ub9cfl1dfLzXp1tdRMkLyUoJXhxGiCFTBCKLe9rpnQ0LbCKFpTgi2QmlmsjRLFPNLWtDcNo21veE0X1eaka4Lad2N0BxXvu6Bcd0yEuOtUsUQP0FmrOFYGjCCaMdL03AjWS8kZZ5IJW7TenbTGqT-A0eBzVMMj0ccV7267XbjrZFPTpjRrUb1-EIjh5wQpdweXNAyD8hCm1BGOeSsxF7Kgr_5B92GKvlg1U20jGkJ4oZoTVdqXUgT75zO47ubZ6v47W_Q3R0nGDQ</recordid><startdate>20220913</startdate><enddate>20220913</enddate><creator>Song, Chenghua</creator><creator>Wen, Ruichao</creator><creator>Zhou, Jiaxuan</creator><creator>Zeng, Xiaoyan</creator><creator>Kou, Zi</creator><creator>Zhang, Jia</creator><creator>Wang, Tao</creator><creator>Chang, Pengkang</creator><creator>Lv, Yi</creator><creator>Wu, Rongqian</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7XB</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-3746-9489</orcidid><orcidid>https://orcid.org/0000-0002-1107-7965</orcidid></search><sort><creationdate>20220913</creationdate><title>Antibacterial and Antifungal Properties of a Novel Antimicrobial Peptide GK-19 and Its Application in Skin and Soft Tissue Infections Induced by MRSA or Candida albicans</title><author>Song, Chenghua ; 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subjects | Antibiotics Antimicrobial agents antimicrobial peptides Bacteria Candida albicans Drug resistance Fungi GK-19 Gram-positive bacteria Life sciences MRSA Nosocomial infections Peptides Pulmonary arteries Scanning electron microscopy skin and soft tissue infections Staphylococcus infections |
title | Antibacterial and Antifungal Properties of a Novel Antimicrobial Peptide GK-19 and Its Application in Skin and Soft Tissue Infections Induced by MRSA or Candida albicans |
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