A Novel Peptide Derived from the Transmembrane Domain of Romo1 Is a Promising Candidate for Sepsis Treatment and Multidrug-Resistant Bacteria
The emergence of multidrug-resistant (MDR) bacteria through the abuse and long-term use of antibiotics is a serious health problem worldwide. Therefore, novel antimicrobial agents that can cure an infection from MDR bacteria, especially gram-negative bacteria, are urgently needed. Antimicrobial pept...
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MDPI AG
2021-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/15/8243 |
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| author | Deok-Gyun You Hye-Ra Lee Hong-Kyu Kim Gi-Young Lee Young-Do Yoo |
| author_facet | Deok-Gyun You Hye-Ra Lee Hong-Kyu Kim Gi-Young Lee Young-Do Yoo |
| author_sort | Deok-Gyun You |
| collection | DOAJ |
| description | The emergence of multidrug-resistant (MDR) bacteria through the abuse and long-term use of antibiotics is a serious health problem worldwide. Therefore, novel antimicrobial agents that can cure an infection from MDR bacteria, especially gram-negative bacteria, are urgently needed. Antimicrobial peptides, part of the innate immunity system, have been studied to find bactericidal agents potent against MDR bacteria. However, they have many problems, such as restrained systemic activity and cytotoxicity. In a previous study, we suggested that the K58–R78 domain of Romo1, a mitochondrial protein encoded by the nucleus, was a promising treatment candidate for sepsis caused by MDR bacteria. Here, we performed sequence optimization to enhance the antimicrobial activity of this peptide and named it as AMPR-22 (antimicrobial peptide derived from Romo1). It showed broad-spectrum antimicrobial activity against 17 sepsis-causing bacteria, including MDR strains, by inducing membrane permeabilization. Moreover, treatment with AMPR-22 enabled a remarkable survival rate in mice injected with MDR bacteria in a murine model of sepsis. Based on these results, we suggest that AMPR-22 could be prescribed as a first-line therapy (prior to bacterial identification) for patients diagnosed with sepsis. |
| first_indexed | 2024-03-10T09:13:54Z |
| format | Article |
| id | doaj.art-49b5bddd5a784737adbb1d7e979a2b0d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:13:54Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-49b5bddd5a784737adbb1d7e979a2b0d2023-11-22T05:45:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012215824310.3390/ijms22158243A Novel Peptide Derived from the Transmembrane Domain of Romo1 Is a Promising Candidate for Sepsis Treatment and Multidrug-Resistant BacteriaDeok-Gyun You0Hye-Ra Lee1Hong-Kyu Kim2Gi-Young Lee3Young-Do Yoo4Laboratory of Molecular Cell Biology, Graduate School of Medicines, Korea University College of Medicine, Korea University, Seoul 02841, KoreaLaboratory of Molecular Cell Biology, Graduate School of Medicines, Korea University College of Medicine, Korea University, Seoul 02841, KoreaDepartment of Surgery, Seoul National University College of Medicine, Seoul 03080, KoreaLaboratory of Molecular Cell Biology, Graduate School of Medicines, Korea University College of Medicine, Korea University, Seoul 02841, KoreaLaboratory of Molecular Cell Biology, Graduate School of Medicines, Korea University College of Medicine, Korea University, Seoul 02841, KoreaThe emergence of multidrug-resistant (MDR) bacteria through the abuse and long-term use of antibiotics is a serious health problem worldwide. Therefore, novel antimicrobial agents that can cure an infection from MDR bacteria, especially gram-negative bacteria, are urgently needed. Antimicrobial peptides, part of the innate immunity system, have been studied to find bactericidal agents potent against MDR bacteria. However, they have many problems, such as restrained systemic activity and cytotoxicity. In a previous study, we suggested that the K58–R78 domain of Romo1, a mitochondrial protein encoded by the nucleus, was a promising treatment candidate for sepsis caused by MDR bacteria. Here, we performed sequence optimization to enhance the antimicrobial activity of this peptide and named it as AMPR-22 (antimicrobial peptide derived from Romo1). It showed broad-spectrum antimicrobial activity against 17 sepsis-causing bacteria, including MDR strains, by inducing membrane permeabilization. Moreover, treatment with AMPR-22 enabled a remarkable survival rate in mice injected with MDR bacteria in a murine model of sepsis. Based on these results, we suggest that AMPR-22 could be prescribed as a first-line therapy (prior to bacterial identification) for patients diagnosed with sepsis.https://www.mdpi.com/1422-0067/22/15/8243AMPR-11Romo1peptide antibioticsdrug resistancemultidrug-resistant bacteriasepsis |
| spellingShingle | Deok-Gyun You Hye-Ra Lee Hong-Kyu Kim Gi-Young Lee Young-Do Yoo A Novel Peptide Derived from the Transmembrane Domain of Romo1 Is a Promising Candidate for Sepsis Treatment and Multidrug-Resistant Bacteria International Journal of Molecular Sciences AMPR-11 Romo1 peptide antibiotics drug resistance multidrug-resistant bacteria sepsis |
| title | A Novel Peptide Derived from the Transmembrane Domain of Romo1 Is a Promising Candidate for Sepsis Treatment and Multidrug-Resistant Bacteria |
| title_full | A Novel Peptide Derived from the Transmembrane Domain of Romo1 Is a Promising Candidate for Sepsis Treatment and Multidrug-Resistant Bacteria |
| title_fullStr | A Novel Peptide Derived from the Transmembrane Domain of Romo1 Is a Promising Candidate for Sepsis Treatment and Multidrug-Resistant Bacteria |
| title_full_unstemmed | A Novel Peptide Derived from the Transmembrane Domain of Romo1 Is a Promising Candidate for Sepsis Treatment and Multidrug-Resistant Bacteria |
| title_short | A Novel Peptide Derived from the Transmembrane Domain of Romo1 Is a Promising Candidate for Sepsis Treatment and Multidrug-Resistant Bacteria |
| title_sort | novel peptide derived from the transmembrane domain of romo1 is a promising candidate for sepsis treatment and multidrug resistant bacteria |
| topic | AMPR-11 Romo1 peptide antibiotics drug resistance multidrug-resistant bacteria sepsis |
| url | https://www.mdpi.com/1422-0067/22/15/8243 |
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