Riboflavin-Vancomycin Conjugate Enables Simultaneous Antibiotic Photo-Release and Photodynamic Killing against Resistant Gram-Positive Pathogens

Bethany Mills, Alex Kiang, Syam Mohan P. C. Mohanan, Mark Bradley, Maxime Klausen

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Decades of antibiotic misuse have led to alarming levels of antimicrobial resistance, and the development of alternative diagnostic and therapeutic strategies to delineate and treat infections is a global priority. In particular, the nosocomial, multidrug-resistant “ESKAPE” pathogens such as Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus spp (VRE) urgently require alternative treatments. Here, we developed light-activated molecules based on the conjugation of the FDA-approved photosensitizer riboflavin to the Gram-positive specific ligand vancomycin to enable targeted antimicrobial photodynamic therapy. The riboflavin-vancomycin conjugate proved to be a potent and versatile antibacterial agent, enabling the rapid, light-mediated, killing of MRSA and VRE with no significant off-target effects. The attachment of riboflavin on vancomycin also led to an increase in antibiotic activity against S. aureus and VRE. Simultaneously, we evidenced for the first time that the flavin subunit undergoes an efficient photoinduced bond cleavage reaction to release vancomycin, thereby acting as a photoremovable protecting group with potential applications in drug delivery.
Original languageEnglish
Pages (from-to)3014-3023
JournalJACS Au
Volume3
Issue number11
DOIs
Publication statusPublished - 24 Oct 2023

Keywords / Materials (for Non-textual outputs)

  • photodynamic therapy
  • photolabile protecting groups
  • uncaging
  • antimicrobial resistance
  • antibiotic
  • ESKAPE pathogens

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