Feng Yanfang, Palanisami Akilan, Ashraf Shoaib, Bhayana Brijesh, Hasan Tayyaba
Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Health Sciences and Technology (Harvard-MIT), Cambridge, Massachusetts, USA.
Photodiagnosis Photodyn Ther. 2020 Jun;30:101693. doi: 10.1016/j.pdpdt.2020.101693. Epub 2020 Mar 12.
The global emergence of carbapenemases in bacterial pathogens has rendered many life-threatening infections untreatable. Even though using carbapenemase inhibitors are a proven strategy in the battle against bacterial carbapenem resistance, developing inhibitors that could universally inactivate all bacterial carbapenemases is extremely challenging given the large diversity and the continuous evolution of bacterial carbapenemases. Antimicrobial photodynamic therapy (aPDT), an upcoming antimicrobial therapy, is demonstrated here for the first time to be a generalized approach to impair the bacterial carbapenemases without being limited by the molecular identities of the carbapenemases. In addition, aPDT is shown to prevent carbapenem antibiotic degradation, thereby enhancing the efficacy of carbapenem antibiotic against the carbapenemase-producing pathogens. Besides the enzyme activity impairment, aPDT was documented here to be genetically toxic for bacteria, and thus radically damage the carbapenemase genetic determinants in bacteria and prevent the transmission of carbapenemases among pathogens. By leveraging the universal carbapenemase-inactivating property of aPDT, it may be possible to make the incurable infections caused by the bacterial carbapenemases susceptible to carbapenem again.
细菌病原体中碳青霉烯酶在全球范围内的出现，已使许多危及生命的感染变得无法治疗。尽管使用碳青霉烯酶抑制剂是对抗细菌碳青霉烯耐药性的一种经证实的策略，但鉴于细菌碳青霉烯酶的多样性巨大且不断进化，开发能够普遍使所有细菌碳青霉烯酶失活的抑制剂极具挑战性。抗菌光动力疗法（aPDT）是一种新兴的抗菌疗法，本文首次证明它是一种通用方法，可损害细菌碳青霉烯酶，而不受碳青霉烯酶分子特性的限制。此外，aPDT被证明可防止碳青霉烯类抗生素降解，从而增强碳青霉烯类抗生素对产碳青霉烯酶病原体的疗效。除了酶活性受损外，本文还证明aPDT对细菌具有遗传毒性，从而从根本上破坏细菌中的碳青霉烯酶遗传决定因素，并防止碳青霉烯酶在病原体之间传播。通过利用aPDT普遍的碳青霉烯酶失活特性，有可能使由细菌碳青霉烯酶引起的无法治愈的感染再次对碳青霉烯类药物敏感。
