Increasing antibiotic activity by rapid bioorthogonal conjugation of drug to resistant bacteria using an upconverted light-activated photocatalyst

Antibiotic vancomycin (Van) is often used as the drug of last resort to treat methicillin resistant Staphylococcus aureus . Due to the emergence of Van-resistant microbes, it is necessary to continuously design strategies to increase the efficacy of Van against resistant cells. In this study, an eff...

Full description

Saved in:
Bibliographic Details
Published in:Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2021-04, Vol.9 (14), p.3136-3142
Main Authors: Du, Quanchao, Wu, Xiangyang, Bi, Wuguo, Xing, Bengang, Yeow, Edwin K. L
Format: Article
Language:English
Subjects:
Antibiotics
Bacteria
Biosynthesis
Cell walls
Conjugation
Drug resistance
Energy transfer
Methicillin
Microorganisms
Minimum inhibitory concentration
Mode of action
Nanocrystals
Near infrared radiation
Peptidoglycans
Toluidine
Toluidine blue
Vancomycin
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Antibiotic vancomycin (Van) is often used as the drug of last resort to treat methicillin resistant Staphylococcus aureus . Due to the emergence of Van-resistant microbes, it is necessary to continuously design strategies to increase the efficacy of Van against resistant cells. In this study, an efficient method of bio-conjugating Van to bacteria is proposed using near-infrared (NIR)-light activation. A Nd 3+ -sensitized upconversion nanocrystal (UCNC) decorated with toluidine blue O (TB) on its surface undergoes upconverted energy transfer from the UCNC to TB when excited by 808 nm light. The photoexcited TB then catalyses the conversion of the dihydrotetrazine (dHTz) moiety in a Van-dHTz conjugate system to tetrazine which undergoes an efficient inverse electron demand Diels-Alder reaction with prior attached norbornene molecules on bacterial cell walls. The enhanced affinity of Van to bacteria by covalent bonding improves the activity of the drug against drug-resistant Enterococci, and the MIC is reduced by 6- to 7-fold as compared to neat Van. We demonstrate that the mode of action is due to increased inhibition of peptidoglycan cell wall biosynthesis. The findings in this study demonstrate that on-demand NIR-light activated bioorthogonal conjugation of Van to microbes is a viable alternative treatment in combating drug-resistant bacteria. A NIR-light activated upconversion nanocrystal transfers energy to dye molecules that photocatalyze the bioorthogonal conjugation of the antibiotic to drug-resistant bacteria for enhanced treatment efficacy.
ISSN:2050-750X
2050-7518
DOI:10.1039/d0tb02568b