Targeting the phosphatidylglycerol lipid: An amphiphilic dendrimer as a promising antibacterial candidate - Archive ouverte HAL
Article Dans Une Revue Science Advances Année : 2024

Targeting the phosphatidylglycerol lipid: An amphiphilic dendrimer as a promising antibacterial candidate

Nian Zhang
Shanny Hsuan Kuo
Shi Qian Lew
Pankaj Patil
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Raleb Taher
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Sanika Vaidya
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Myung Whan Oh
Sook Yin Chong
Jun Zheng
Oleg Rouvinski
Williams Abolarin
Sabrina Pricl
Gee Lau
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Leo Tsz On Lee
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Résumé

The rapid emergence and spread of multidrug-resistant bacterial pathogens require the development of antibacterial agents that are robustly effective while inducing no toxicity or resistance development. In this context, we designed and synthesized amphiphilic dendrimers as antibacterial candidates. We report the promising potent antibacterial activity shown by the amphiphilic dendrimer AD1b , composed of a long hydrophobic alkyl chain and a tertiary amine-terminated poly(amidoamine) dendron, against a panel of Gram-negative bacteria, including multidrug-resistant Escherichia coli and Acinetobacter baumannii. AD1b exhibited effective activity against drug-resistant bacterial infections in vivo. Mechanistic studies revealed that AD1b targeted the membrane phospholipids phosphatidylglycerol (PG) and cardiolipin (CL), leading to the disruption of the bacterial membrane and proton motive force, metabolic disturbance, leakage of cellular components, and, ultimately, cell death. Together, AD1b that specifically interacts with PG/CL in bacterial membranes supports the use of small amphiphilic dendrimers as a promising strategy to target drug-resistant bacterial pathogens and addresses the global antibiotic crisis.
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Dates et versions

hal-04710306 , version 1 (26-09-2024)

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Nian Zhang, Dinesh Dhumal, Shanny Hsuan Kuo, Shi Qian Lew, Pankaj Patil, et al.. Targeting the phosphatidylglycerol lipid: An amphiphilic dendrimer as a promising antibacterial candidate. Science Advances , 2024, 10 (39), pp.eadn8117. ⟨10.1126/sciadv.adn8117⟩. ⟨hal-04710306⟩
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