Amphipathic Peptide Antibiotics with Potent Activity against Multidrug-Resistant Pathogens
The emergence and prevalence of multidrug-resistant (MDR) bacteria have posed a serious threat to public health. Of particular concern are methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) and <i>bla</i><sub>NDM</sub>, <i>mcr-1</i> and <i>...
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| Format: | Article |
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MDPI AG
2021-03-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/4/438 |
| _version_ | 1797540260059545600 |
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| author | Jingru Shi Chen Chen Dejuan Wang Ziwen Tong Zhiqiang Wang Yuan Liu |
| author_facet | Jingru Shi Chen Chen Dejuan Wang Ziwen Tong Zhiqiang Wang Yuan Liu |
| author_sort | Jingru Shi |
| collection | DOAJ |
| description | The emergence and prevalence of multidrug-resistant (MDR) bacteria have posed a serious threat to public health. Of particular concern are methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) and <i>bla</i><sub>NDM</sub>, <i>mcr-1</i> and <i>tet</i>(X)-positive Gram-negative pathogens. The fact that few new antibiotics have been approved in recent years exacerbates this global crisis, thus, new alternatives are urgently needed. Antimicrobial peptides (AMPs) originated from host defense peptides with a wide range of sources and multiple functions, are less prone to achieve resistance. All these characteristics laid the foundation for AMPs to become potential antibiotic candidates. In this study, we revealed that peptide WW307 displayed potent antibacterial and bactericidal activity against MDR bacteria, including MRSA and Gram-negative bacteria carrying <i>bla</i><sub>NDM-5</sub>, <i>mcr-1</i> or <i>tet</i>(X4). In addition, WW307 exhibited great biofilm inhibition and eradication activity. Safety and stability experiments showed that WW307 had a strong resistance against various physiological conditions and displayed relatively low toxicity. Mechanistic experiments showed that WW307 resulted in membrane damage by selectively targeting bacterial membrane-specific components, including lipopolysaccharide (LPS), phosphatidylglycerol (PG), and cardiolipin (CL). Moreover, WW307 dissipated membrane potential and triggered the production of reactive oxygen species (ROS). Collectively, these results demonstrated that WW307 represents a promising candidate for combating MDR pathogens. |
| first_indexed | 2024-03-10T12:57:33Z |
| format | Article |
| id | doaj.art-e44af635adb240ec8af45252b934df60 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T12:57:33Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-e44af635adb240ec8af45252b934df602023-11-21T11:48:08ZengMDPI AGPharmaceutics1999-49232021-03-0113443810.3390/pharmaceutics13040438Amphipathic Peptide Antibiotics with Potent Activity against Multidrug-Resistant PathogensJingru Shi0Chen Chen1Dejuan Wang2Ziwen Tong3Zhiqiang Wang4Yuan Liu5College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou 225009, ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou 225009, ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou 225009, ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou 225009, ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou 225009, ChinaThe emergence and prevalence of multidrug-resistant (MDR) bacteria have posed a serious threat to public health. Of particular concern are methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) and <i>bla</i><sub>NDM</sub>, <i>mcr-1</i> and <i>tet</i>(X)-positive Gram-negative pathogens. The fact that few new antibiotics have been approved in recent years exacerbates this global crisis, thus, new alternatives are urgently needed. Antimicrobial peptides (AMPs) originated from host defense peptides with a wide range of sources and multiple functions, are less prone to achieve resistance. All these characteristics laid the foundation for AMPs to become potential antibiotic candidates. In this study, we revealed that peptide WW307 displayed potent antibacterial and bactericidal activity against MDR bacteria, including MRSA and Gram-negative bacteria carrying <i>bla</i><sub>NDM-5</sub>, <i>mcr-1</i> or <i>tet</i>(X4). In addition, WW307 exhibited great biofilm inhibition and eradication activity. Safety and stability experiments showed that WW307 had a strong resistance against various physiological conditions and displayed relatively low toxicity. Mechanistic experiments showed that WW307 resulted in membrane damage by selectively targeting bacterial membrane-specific components, including lipopolysaccharide (LPS), phosphatidylglycerol (PG), and cardiolipin (CL). Moreover, WW307 dissipated membrane potential and triggered the production of reactive oxygen species (ROS). Collectively, these results demonstrated that WW307 represents a promising candidate for combating MDR pathogens.https://www.mdpi.com/1999-4923/13/4/438antimicrobial peptideantibiotic resistancemultidrug-resistant bacteriamembrane damage |
| spellingShingle | Jingru Shi Chen Chen Dejuan Wang Ziwen Tong Zhiqiang Wang Yuan Liu Amphipathic Peptide Antibiotics with Potent Activity against Multidrug-Resistant Pathogens Pharmaceutics antimicrobial peptide antibiotic resistance multidrug-resistant bacteria membrane damage |
| title | Amphipathic Peptide Antibiotics with Potent Activity against Multidrug-Resistant Pathogens |
| title_full | Amphipathic Peptide Antibiotics with Potent Activity against Multidrug-Resistant Pathogens |
| title_fullStr | Amphipathic Peptide Antibiotics with Potent Activity against Multidrug-Resistant Pathogens |
| title_full_unstemmed | Amphipathic Peptide Antibiotics with Potent Activity against Multidrug-Resistant Pathogens |
| title_short | Amphipathic Peptide Antibiotics with Potent Activity against Multidrug-Resistant Pathogens |
| title_sort | amphipathic peptide antibiotics with potent activity against multidrug resistant pathogens |
| topic | antimicrobial peptide antibiotic resistance multidrug-resistant bacteria membrane damage |
| url | https://www.mdpi.com/1999-4923/13/4/438 |
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