Photodynamic inactivation of bacterial carbapenemases restores bacterial carbapenem susceptibility and enhances carbapenem antibiotic effectiveness

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.