Rapid detection of major Gram-positive pathogens in ocular specimens using a novel fluorescent vancomycin-based probe

Sharma, Ritu; Harinee, Rajagopalan; Klausen, Maxime; Jeyalatha, M. Vimalin; Üçüncü, Muhammed; Venkateswaran, Seshasailam; Anand, Appakkudal R.; Bradley, Mark

doi:10.1039/d2sd00061j

Cited by 4 publications

(1 citation statement)

References 24 publications

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“…The preparation of the vancomycin derivative (compound 6, Figure 1) required additional steps because vancomycin contains multiple reactive sites for derivatization. We selected the aminoglycan chain of vancomycin as the preferred conjugation site given that this position is not essential for binding to the bacterial cell wall [24], and that it has previously been modified with fluorescent dyes without negatively affecting the recognition of Gram-positive bacteria [25][26][27][28]. The synthesis of compound 6 was designed in three steps.…”

Section: Chemical Synthesis Of Nitrobenzoselenadiazole Apdt Agentsmentioning

confidence: 99%

Environmentally sensitive photosensitizers enable targeted photodynamic ablation of Gram-positive antibiotic resistant bacteria

Benson¹,

Kiang²,

Lochenie³

et al. 2023

Theranostics

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Bacterial infections remain among the biggest challenges to human health, leading to high antibiotic usage, morbidity, hospitalizations, and accounting for approximately 8 million deaths worldwide every year. The overuse of antibiotics and paucity of antimicrobial innovation has led to antimicrobial resistant pathogens that threaten to reverse key advances of modern medicine. Photodynamic therapeutics can kill bacteria but there are few agents that can ablate pathogens with minimal off-target effects. Methods: We describe nitrobenzoselenadiazoles as some of the first environmentally sensitive organic photosensitizers, and their adaptation to produce theranostics with optical detection and light-controlled antimicrobial activity. We combined nitrobenzoselenadiazoles with bacteria-targeting moieties (i.e., glucose-6-phosphate, amoxicillin, vancomycin) producing environmentally sensitive photodynamic agents. Results: The labelled vancomycin conjugate was able to both visualize and eradicate multidrug resistant Gram-positive ESKAPE pathogens at nanomolar concentrations, including clinical isolates and those that form biofilms. Conclusion: Nitrobenzoselenadiazole conjugates are easily synthesized and display strong environment dependent ROS production. Due to their small size and non-invasive character, they unobtrusively label antimicrobial targeting moieties. We envisage that the simplicity and modularity of this chemical strategy will accelerate the rational design of new antimicrobial therapies for refractory bacterial infections.

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