Light-activated molecular machines are fast-acting broad-spectrum antibacterials that target the membrane.

Autor: Santos AL; Department of Chemistry, Rice University, Houston, TX 77005, USA.; IdISBA-Fundación de Investigación Sanitaria de las Islas Baleares, Palma, Spain., Liu D; Department of Chemistry, Rice University, Houston, TX 77005, USA., Reed AK; Department of Chemistry, Rice University, Houston, TX 77005, USA., Wyderka AM; Department of Chemistry, Rice University, Houston, TX 77005, USA., van Venrooy A; Department of Chemistry, Rice University, Houston, TX 77005, USA., Li JT; Department of Chemistry, Rice University, Houston, TX 77005, USA., Li VD; Department of Chemistry, Rice University, Houston, TX 77005, USA., Misiura M; Department of Chemistry, Rice University, Houston, TX 77005, USA., Samoylova O; Department of Chemistry, Rice University, Houston, TX 77005, USA., Beckham JL; Department of Chemistry, Rice University, Houston, TX 77005, USA., Ayala-Orozco C; Department of Chemistry, Rice University, Houston, TX 77005, USA., Kolomeisky AB; Department of Chemistry, Rice University, Houston, TX 77005, USA., Alemany LB; Department of Chemistry, Rice University, Houston, TX 77005, USA.; Shared Equipment Authority, Rice University, Houston, TX 77005, USA., Oliver A; IdISBA-Fundación de Investigación Sanitaria de las Islas Baleares, Palma, Spain.; Servicio de Microbiologia, Hospital Universitari Son Espases, Palma, Spain., Tegos GP; Office of Research, Reading Hospital, Tower Health, 420 S. Fifth Avenue, West Reading, PA 19611, USA., Tour JM; Department of Chemistry, Rice University, Houston, TX 77005, USA.; Smalley-Curl Institute, Rice University, Houston, TX 77005, USA.; Department of Materials Science and NanoEngineering, Rice University, Houston, TX 77005, USA.; NanoCarbon Center and the Welch Institute for Advanced Materials, Rice University, Houston, TX 77005, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2022 Jun 03; Vol. 8 (22), pp. eabm2055. Date of Electronic Publication: 2022 Jun 01.
DOI: 10.1126/sciadv.abm2055
Abstrakt: The increasing occurrence of antibiotic-resistant bacteria and the dwindling antibiotic research and development pipeline have created a pressing global health crisis. Here, we report the discovery of a distinctive antibacterial therapy that uses visible (405 nanometers) light-activated synthetic molecular machines (MMs) to kill Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus , in minutes, vastly outpacing conventional antibiotics. MMs also rapidly eliminate persister cells and established bacterial biofilms. The antibacterial mode of action of MMs involves physical disruption of the membrane. In addition, by permeabilizing the membrane, MMs at sublethal doses potentiate the action of conventional antibiotics. Repeated exposure to antibacterial MMs is not accompanied by resistance development. Finally, therapeutic doses of MMs mitigate mortality associated with bacterial infection in an in vivo model of burn wound infection. Visible light-activated MMs represent an unconventional antibacterial mode of action by mechanical disruption at the molecular scale, not existent in nature and to which resistance development is unlikely.
Databáze: MEDLINE