Highlighting the Potential of LyeTx I, a Peptide Derived from the Venom of the Spider <i>Lycosa erythrognatha</i>, as a Potential Prototype for the Development of a New Antimicrobial Against Carbapenem-Resistant <i>Klebsiella pneumoniae</i>
<b>Background</b>: Carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP) is a multidrug-resistant (MDR) gram-negative bacterium frequently involved in hospital-acquired pneumonia. The infection caused by this superbug has spread quickly in health centers worldwide, leading...
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2025-05-01
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| author | William Gustavo Lima Amanda Souza Félix Felipe Rocha da Silva Santos Fernanda de Lima Tana Amanda Neves de Souza Rodrigo Moreira Verly Maria Elena de Lima |
| author_facet | William Gustavo Lima Amanda Souza Félix Felipe Rocha da Silva Santos Fernanda de Lima Tana Amanda Neves de Souza Rodrigo Moreira Verly Maria Elena de Lima |
| author_sort | William Gustavo Lima |
| collection | DOAJ |
| description | <b>Background</b>: Carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP) is a multidrug-resistant (MDR) gram-negative bacterium frequently involved in hospital-acquired pneumonia. The infection caused by this superbug has spread quickly in health centers worldwide, leading to high mortality rates. Due to this emerging scenario, the World Health Organization has categorized CRKP as the highest-priority species for the development of new compounds. In this context, antimicrobial peptides (AMPs) stand out as prototypes for alternative antimicrobials against superbugs, including CRKP. <b>Objectives</b>: We aimed to describe the antibacterial effect of an AMP (LyeTx I), derived from the venom of the spider <i>Lycosa erythrognatha</i>, against CRKP in vitro and in a murine pneumonia model. <b>Results</b>: LyeTx I showed antibacterial effects against all the CRKP clinical isolates tested, with a minimum inhibitory concentration (MIC) range of 2–8 µM and a minimum bactericidal concentration (MBC) range of 2–16 µM. The microbial anionic membrane was the primary target of LyeTx I, which acts by displacing divalent cations bound to this structure in a manner similar to that of polymyxins. Notably, LyeTx I displayed significant lytic activity against mimetic membranes, indicating its potential to disrupt bacterial cell integrity. In in vivo assays, the LyeTx I peptide proved to be safe at a dose of 10 mg/kg. In addition, intraperitoneal use of LyeTx I reduced the bacterial load and inflammation in the lungs of animals infected with a hypervirulent strain of CRKP. <b>Conclusions</b>: These results indicate that LyeTx I is a potential prototype for the development of new antibacterials against MDR species, such as CRKP. |
| format | Article |
| id | doaj-art-e69c10174ba64591a2556099b60ee4ca |
| institution | OA Journals |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj-art-e69c10174ba64591a2556099b60ee4ca2025-08-20T01:56:35ZengMDPI AGPharmaceuticals1424-82472025-05-0118567910.3390/ph18050679Highlighting the Potential of LyeTx I, a Peptide Derived from the Venom of the Spider <i>Lycosa erythrognatha</i>, as a Potential Prototype for the Development of a New Antimicrobial Against Carbapenem-Resistant <i>Klebsiella pneumoniae</i>William Gustavo Lima0Amanda Souza Félix1Felipe Rocha da Silva Santos2Fernanda de Lima Tana3Amanda Neves de Souza4Rodrigo Moreira Verly5Maria Elena de Lima6Programa de Pós-Graduação Stricto Sensu em Medicina e Biomedicina, Faculdade Santa Casa de Belo Horizonte, Belo Horizonte 30150-221, MG, BrazilDepartamento de Química, Instituto de Ciências Exatas, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Diamantina 39100-000, MG, BrazilInstituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, BrazilInstituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, BrazilDepartamento de Química, Instituto de Ciências Exatas, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Diamantina 39100-000, MG, BrazilDepartamento de Química, Instituto de Ciências Exatas, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Diamantina 39100-000, MG, BrazilPrograma de Pós-Graduação Stricto Sensu em Medicina e Biomedicina, Faculdade Santa Casa de Belo Horizonte, Belo Horizonte 30150-221, MG, Brazil<b>Background</b>: Carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP) is a multidrug-resistant (MDR) gram-negative bacterium frequently involved in hospital-acquired pneumonia. The infection caused by this superbug has spread quickly in health centers worldwide, leading to high mortality rates. Due to this emerging scenario, the World Health Organization has categorized CRKP as the highest-priority species for the development of new compounds. In this context, antimicrobial peptides (AMPs) stand out as prototypes for alternative antimicrobials against superbugs, including CRKP. <b>Objectives</b>: We aimed to describe the antibacterial effect of an AMP (LyeTx I), derived from the venom of the spider <i>Lycosa erythrognatha</i>, against CRKP in vitro and in a murine pneumonia model. <b>Results</b>: LyeTx I showed antibacterial effects against all the CRKP clinical isolates tested, with a minimum inhibitory concentration (MIC) range of 2–8 µM and a minimum bactericidal concentration (MBC) range of 2–16 µM. The microbial anionic membrane was the primary target of LyeTx I, which acts by displacing divalent cations bound to this structure in a manner similar to that of polymyxins. Notably, LyeTx I displayed significant lytic activity against mimetic membranes, indicating its potential to disrupt bacterial cell integrity. In in vivo assays, the LyeTx I peptide proved to be safe at a dose of 10 mg/kg. In addition, intraperitoneal use of LyeTx I reduced the bacterial load and inflammation in the lungs of animals infected with a hypervirulent strain of CRKP. <b>Conclusions</b>: These results indicate that LyeTx I is a potential prototype for the development of new antibacterials against MDR species, such as CRKP.https://www.mdpi.com/1424-8247/18/5/679carbapenem-resistant <i>Klebsiella pneumoniae</i>superbugantimicrobial peptidesspider venompneumoniaantimicrobial therapy |
| spellingShingle | William Gustavo Lima Amanda Souza Félix Felipe Rocha da Silva Santos Fernanda de Lima Tana Amanda Neves de Souza Rodrigo Moreira Verly Maria Elena de Lima Highlighting the Potential of LyeTx I, a Peptide Derived from the Venom of the Spider <i>Lycosa erythrognatha</i>, as a Potential Prototype for the Development of a New Antimicrobial Against Carbapenem-Resistant <i>Klebsiella pneumoniae</i> Pharmaceuticals carbapenem-resistant <i>Klebsiella pneumoniae</i> superbug antimicrobial peptides spider venom pneumonia antimicrobial therapy |
| title | Highlighting the Potential of LyeTx I, a Peptide Derived from the Venom of the Spider <i>Lycosa erythrognatha</i>, as a Potential Prototype for the Development of a New Antimicrobial Against Carbapenem-Resistant <i>Klebsiella pneumoniae</i> |
| title_full | Highlighting the Potential of LyeTx I, a Peptide Derived from the Venom of the Spider <i>Lycosa erythrognatha</i>, as a Potential Prototype for the Development of a New Antimicrobial Against Carbapenem-Resistant <i>Klebsiella pneumoniae</i> |
| title_fullStr | Highlighting the Potential of LyeTx I, a Peptide Derived from the Venom of the Spider <i>Lycosa erythrognatha</i>, as a Potential Prototype for the Development of a New Antimicrobial Against Carbapenem-Resistant <i>Klebsiella pneumoniae</i> |
| title_full_unstemmed | Highlighting the Potential of LyeTx I, a Peptide Derived from the Venom of the Spider <i>Lycosa erythrognatha</i>, as a Potential Prototype for the Development of a New Antimicrobial Against Carbapenem-Resistant <i>Klebsiella pneumoniae</i> |
| title_short | Highlighting the Potential of LyeTx I, a Peptide Derived from the Venom of the Spider <i>Lycosa erythrognatha</i>, as a Potential Prototype for the Development of a New Antimicrobial Against Carbapenem-Resistant <i>Klebsiella pneumoniae</i> |
| title_sort | highlighting the potential of lyetx i a peptide derived from the venom of the spider i lycosa erythrognatha i as a potential prototype for the development of a new antimicrobial against carbapenem resistant i klebsiella pneumoniae i |
| topic | carbapenem-resistant <i>Klebsiella pneumoniae</i> superbug antimicrobial peptides spider venom pneumonia antimicrobial therapy |
| url | https://www.mdpi.com/1424-8247/18/5/679 |
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