2. Academic Validation
  3. AMXT-1501 targets membrane phospholipids against Gram-positive and -negative multidrug-resistant bacteria

AMXT-1501 targets membrane phospholipids against Gram-positive and -negative multidrug-resistant bacteria

  • Emerg Microbes Infect. 2024 Dec;13(1):2321981. doi: 10.1080/22221751.2024.2321981.
Jinxin Zheng 1,  Xiaoju Liu 1,  Yanpeng Xiong 1,  Qingyin Meng 1,  Peiyu Li 1,  Fan Zhang 1 2,  Xiaoming Liu 3,  Zhiwei Lin 1,  Qiwen Deng 1,  Zewen Wen 1,  Zhijian Yu 1
Affiliations

Affiliations

  • 1 Department of Infectious Diseases and Shenzhen Key Lab of Endogenous Infection, Shenzhen Nanshan People's Hospital and the 6th Affiliated Hospital of Shenzhen University Medical School, Shenzhen, People's Republic of China.
  • 2 Department of Tuberculosis, Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, People's Republic of China.
  • 3 Department of Gastroenterology, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, People's Republic of China.
PMID: 38422452 DOI: 10.1080/22221751.2024.2321981
Abstract

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.

Keywords

AMXT-1501; CRE; Cardiolipin; ESBL; MRSA; Multidrug-resistant; Phosphatidylglycerol.

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