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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Emerging microbes & infections - 13(2024), 1 vom: 29. März, Seite 2321981 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zheng, Jinxin [VerfasserIn] |
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| Links: |
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| Themen: |
AMXT-1501 |
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| Anmerkungen: |
Date Completed 04.03.2024 Date Revised 04.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/22221751.2024.2321981 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369123476 |
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| 520 | |a 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 | ||
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| 650 | 4 | |a AMXT-1501 | |
| 650 | 4 | |a CRE | |
| 650 | 4 | |a Cardiolipin | |
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| 650 | 4 | |a Phosphatidylglycerol | |
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| 700 | 1 | |a Liu, Xiaoju |e verfasserin |4 aut | |
| 700 | 1 | |a Xiong, Yanpeng |e verfasserin |4 aut | |
| 700 | 1 | |a Meng, Qingyin |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Peiyu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Fan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xiaoming |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Zhiwei |e verfasserin |4 aut | |
| 700 | 1 | |a Deng, Qiwen |e verfasserin |4 aut | |
| 700 | 1 | |a Wen, Zewen |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Zhijian |e verfasserin |4 aut | |
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