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Rapid Detection of Drug Resistance in Patients Suffering from Invasive Fungal Infections

Global epidemics of fungal infections caused by drug resistant pathogens has been
rising sharply in recent decades including the most recently discovered Candida auris
(an extensive multi-drug resistant fungal pathogen). The Echioncandin class of
antifungal drugs approved as the first-line treatment of candidaemia, invasive
candidiasis and severe infections caused by pathogenic yeast of the genus Candida,
the most prevalent fungal pathogen in humans. Due to the high mortality rate caused
by invasive fungal infection, a rapid and reliable method for detection of drug
resistance is highly important.
Rapid tests for detection of echinocandin resistance are currently unavailable. Current
methods for detection of Echinocandin resistance require laboratory microdilution
methods (EUCAST, CLSI reference methods) or commercial methods (Se nsititre
Yeast One, Vitek, disk diffusion, plastic gradient strips) which are time consuming (at
least 24h to complete) and delay effective treatment.
A rapid and robust echinocandin resistance detection assay utilizes fluorescent probes
that facilitates selection of appropriate drug treatment. The technology will dramatically
reduce the time required to facilitate optimized decisions for treatment of patients
suffering from invasive fungal infections.
The technology detects resistance to the echinocandin class of antifungal drugs in
Candida yeast in close to a 100% certainty in over 80% of the cases therefore
dramatically reduces the decision time required for patient care.

Fluorescent caspofungin probe 1 localizes to vacuoles in yeast cells. DIC and fluorescent images
of C. albicans CG72 cells expressing Ypt72-GFP (green) incubated with probe 1 (1 M, red) for
60 minutes in PBS. Ypt72, is a vacuolar Rab small monomeric GTPase,


There is currently no competing technology which allows rapid (30 minutes)
echinocandin resistance detection and accelerated decision time for the treatment of
Candida infections.
Micha Fridman, Qais Z. Jaber, Judith Berman. "Caspofungin Derivatives and Assays
for Evaluating Antifungal Treatment Efficacy". U.S. Provisional Patent Application No.
63/066,407 filed 17 August (2020).
Jaber, Qais Z; Bibi, Maayan; Ksiezopolska, Ewa; Gabaldon, Toni; Berman, Judith*;
Fridman, Micha*. Elevated Vacuolar Uptake of Fluorescently Labeled Antifungal Drug
Caspofungin Predicts Echinocandin Resistance in Pathogenic Yeast. ACS Central
Science. 2020, 6(10), 1698-1712. IF: 12.685, Number of citations: 2, Rank: 16/177
manuscript was highlighted in a commentary paper: Boon Shing, Loh, Wee Han,
Ang*. “Illuminating” Echinocandins’ Mechanism of Action. ACS Central Science. 2020,
6(10), 1651-1653.