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

Autor: Zhang N; Faculty of Health Sciences, University of Macau, Taipa, Macau, China., Dhumal D; Aix-Marseille Universite, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille, UMR 7325, 'Equipe Labellisee Ligue Contre le Cancer,' 13288 Marseille, France., Kuo SH; Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, IL, USA., Lew SQ; Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, IL, USA., Patil PD; Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, MA, USA., Taher R; Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, MA, USA., Vaidya S; Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, MA, USA., Galanakou C; Aix-Marseille Universite, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille, UMR 7325, 'Equipe Labellisee Ligue Contre le Cancer,' 13288 Marseille, France., Elkihel A; Aix-Marseille Universite, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille, UMR 7325, 'Equipe Labellisee Ligue Contre le Cancer,' 13288 Marseille, France., Oh MW; Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, IL, USA., Chong SY; Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, IL, USA., Marson D; Molecular Biology and Nanotechnology Laboratory (MolBNL@UniTS), DEA, University of Trieste, Trieste, Italy., Zheng J; Faculty of Health Sciences, University of Macau, Taipa, Macau, China., Rouvinski O; Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, MA, USA., Abolarin WO; Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, MA, USA., Pricl S; Molecular Biology and Nanotechnology Laboratory (MolBNL@UniTS), DEA, University of Trieste, Trieste, Italy.; Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland., Lau GW; Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, IL, USA., Lee LTO; Faculty of Health Sciences, University of Macau, Taipa, Macau, China.; Cancer Centre, Faculty of Health Sciences, University of Macau, Taipa, Macau, China.; Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau, China., Peng L; Aix-Marseille Universite, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille, UMR 7325, 'Equipe Labellisee Ligue Contre le Cancer,' 13288 Marseille, France.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2024 Sep 27; Vol. 10 (39), pp. eadn8117. Date of Electronic Publication: 2024 Sep 25.
DOI: 10.1126/sciadv.adn8117
Abstrakt: 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.
Databáze: MEDLINE