{"title":"AMXT-1501 以膜磷脂为靶标,可对抗革兰氏阳性和阴性多重耐药菌。","authors":"Jinxin Zheng, Xiaoju Liu, Yanpeng Xiong, Qingyin Meng, Peiyu Li, Fan Zhang, Xiaoming Liu, Zhiwei Lin, Qiwen Deng, Zewen Wen, Zhijian Yu","doi":"10.1080/22221751.2024.2321981","DOIUrl":null,"url":null,"abstract":"<p><p>The rapid proliferation of multidrug-resistant (MDR) bacterial pathogens poses a serious threat to healthcare worldwide. Carbapenem-resistant (CR) Enterobacteriaceae, which have near-universal resistance to available antimicrobials, represent a particularly concerning issue. Herein, we report the identification of AMXT-1501, a polyamine transport system inhibitor with antibacterial activity against Gram-positive and -negative MDR bacteria. We observed minimum inhibitory concentration (MIC)<sub>50</sub>/MIC<sub>90</sub> values for AMXT-1501 in the range of 3.13-12.5 μM (2.24-8.93 μg /mL), including for methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), CR <i>Escherichia coli</i>, <i>Klebsiella pneumoniae</i>, and <i>Pseudomonas aeruginosa</i>. AMXT-1501 was more effective against MRSA and CR <i>E. coli</i> than vancomycin and tigecycline, respectively. Subinhibitory concentrations of AMXT-1501 reduced the biofilm formation of <i>S. aureus</i> and <i>Enterococcus faecalis</i>. Mechanistically, AMXT-1501 exposure damaged microbial membranes and increased membrane permeability and membrane potential by binding to cardiolipin (CL) and phosphatidylglycerol (PG). Importantly, AMXT-1501 pressure did not induce resistance readily in the tested pathogens.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":null,"pages":null},"PeriodicalIF":8.4000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10906134/pdf/","citationCount":"0","resultStr":"{\"title\":\"AMXT-1501 targets membrane phospholipids against Gram-positive and -negative multidrug-resistant bacteria.\",\"authors\":\"Jinxin Zheng, Xiaoju Liu, Yanpeng Xiong, Qingyin Meng, Peiyu Li, Fan Zhang, Xiaoming Liu, Zhiwei Lin, Qiwen Deng, Zewen Wen, Zhijian Yu\",\"doi\":\"10.1080/22221751.2024.2321981\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The rapid proliferation of multidrug-resistant (MDR) bacterial pathogens poses a serious threat to healthcare worldwide. Carbapenem-resistant (CR) Enterobacteriaceae, which have near-universal resistance to available antimicrobials, represent a particularly concerning issue. Herein, we report the identification of AMXT-1501, a polyamine transport system inhibitor with antibacterial activity against Gram-positive and -negative MDR bacteria. We observed minimum inhibitory concentration (MIC)<sub>50</sub>/MIC<sub>90</sub> values for AMXT-1501 in the range of 3.13-12.5 μM (2.24-8.93 μg /mL), including for methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), CR <i>Escherichia coli</i>, <i>Klebsiella pneumoniae</i>, and <i>Pseudomonas aeruginosa</i>. AMXT-1501 was more effective against MRSA and CR <i>E. coli</i> than vancomycin and tigecycline, respectively. Subinhibitory concentrations of AMXT-1501 reduced the biofilm formation of <i>S. aureus</i> and <i>Enterococcus faecalis</i>. Mechanistically, AMXT-1501 exposure damaged microbial membranes and increased membrane permeability and membrane potential by binding to cardiolipin (CL) and phosphatidylglycerol (PG). Importantly, AMXT-1501 pressure did not induce resistance readily in the tested pathogens.</p>\",\"PeriodicalId\":11602,\"journal\":{\"name\":\"Emerging Microbes & Infections\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":8.4000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10906134/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Emerging Microbes & Infections\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/22221751.2024.2321981\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/2/29 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Emerging Microbes & Infections","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/22221751.2024.2321981","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/29 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
AMXT-1501 targets membrane phospholipids against Gram-positive and -negative multidrug-resistant bacteria.
The rapid proliferation of multidrug-resistant (MDR) bacterial pathogens poses a serious threat to healthcare worldwide. Carbapenem-resistant (CR) Enterobacteriaceae, which have near-universal resistance to available antimicrobials, represent a particularly concerning issue. Herein, we report the identification of AMXT-1501, a polyamine transport system inhibitor with antibacterial activity against Gram-positive and -negative MDR bacteria. We observed minimum inhibitory concentration (MIC)50/MIC90 values for AMXT-1501 in the range of 3.13-12.5 μM (2.24-8.93 μg /mL), including for methicillin-resistant Staphylococcus aureus (MRSA), CR Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. AMXT-1501 was more effective against MRSA and CR E. coli than vancomycin and tigecycline, respectively. Subinhibitory concentrations of AMXT-1501 reduced the biofilm formation of S. aureus and Enterococcus faecalis. Mechanistically, AMXT-1501 exposure damaged microbial membranes and increased membrane permeability and membrane potential by binding to cardiolipin (CL) and phosphatidylglycerol (PG). Importantly, AMXT-1501 pressure did not induce resistance readily in the tested pathogens.
期刊介绍:
Emerging Microbes & Infections is a peer-reviewed, open-access journal dedicated to publishing research at the intersection of emerging immunology and microbiology viruses.
The journal's mission is to share information on microbes and infections, particularly those gaining significance in both biological and clinical realms due to increased pathogenic frequency. Emerging Microbes & Infections is committed to bridging the scientific gap between developed and developing countries.
This journal addresses topics of critical biological and clinical importance, including but not limited to:
- Epidemic surveillance
- Clinical manifestations
- Diagnosis and management
- Cellular and molecular pathogenesis
- Innate and acquired immune responses between emerging microbes and their hosts
- Drug discovery
- Vaccine development research
Emerging Microbes & Infections invites submissions of original research articles, review articles, letters, and commentaries, fostering a platform for the dissemination of impactful research in the field.