(BOSTON) — A groundbreaking study has unveiled a new diagnostic approach to combat the pathogenic yeast fungus Candida auris (C. auris), a formidable threat in healthcare settings. The fungus, notorious for its antimicrobial resistance, poses significant risks to hospital patients and nursing home residents, particularly those with weakened immune systems. The research, published in Nature Biomedical Engineering, introduces an innovative tool that promises to revolutionize the detection and management of this resilient pathogen.
The announcement comes as hospitals worldwide grapple with the challenges posed by C. auris, which can colonize surfaces for extended periods, defying standard disinfectants. The pathogen is particularly dangerous for patients undergoing organ transplants or chemotherapy, as well as those with compromised immune systems due to conditions like HIV. Once C. auris infections penetrate the bloodstream or vital organs, they become life-threatening, mimicking the symptoms and immune responses associated with bacterial and viral infections.
Understanding C. Auris and Its Challenges
Despite the availability of antifungal medications, C. auris has rapidly developed strains resistant to these treatments, complicating the efforts of healthcare professionals. This resistance often necessitates the use of alternative drugs, which can impose additional burdens on patients. In some cases, infections become untreatable with existing medications, underscoring the urgent need for more effective diagnostic methods.
According to Justin Rolando, Ph.D., a lead author of the study, “Clinicians need a much more effective diagnostic approach to accurately quantify the abundance of the pathogen in patients and assess its antifungal resistance in order to better respond to C. auris infections and help prevent future hospital-associated outbreaks.” Current diagnostic methods are criticized for being costly, slow, and reliant on complex equipment and specialized personnel.
The dSHERLOCK Innovation
The study introduces a precision diagnostic tool named dSHERLOCK, which stands for digital SHERLOCK. This next-generation test, developed by the teams of Wyss Institute Core Faculty members David Walt, Ph.D., and James Collins, Ph.D., leverages CRISPR-based technology to detect pathogen-derived nucleic acid sequences with single nucleotide precision. The tool integrates SHERLOCK technology with ultra-sensitive single-molecule microarray technology and a machine learning-based artificial intelligence method.
By analyzing fluorescent signals from thousands of single-molecule assays in real-time, dSHERLOCK provides a fast and quantitative measure of C. auris colonization in patient samples. It also identifies mutations responsible for antimicrobial resistance (AMR), offering critical insights for optimizing treatment strategies.
“The capabilities that we are introducing with dSHERLOCK satisfy the major clinical requirements for a next-generation assay to rapidly identify and quantify the C. auris burden in easily obtained patient samples,” said James Collins, Wyss Founding Core Faculty member.
Addressing an Urgent Need
In response to several outbreaks of treatment-resistant C. auris infections in 2019, the New York State Department of Health called for accelerated diagnostic advancements. The dSHERLOCK project, funded by the Center, was a direct response to this urgent need. The collaboration involved researchers from the Wyss Institute and the Wadsworth Center Mycology Lab, who provided initial patient samples for technology validation.
Nicole Weckman, Ph.D., a co-first author, emphasized the importance of the tool’s ability to produce distinct fluorescent signatures for different antifungal drugs. This capability allows for the identification of sequence-specific signatures that correlate with defined AMRs against commonly used drugs like azole and echinocandin.
Future Implications and Broader Applications
The dSHERLOCK platform’s potential extends beyond C. auris. David Walt, co-senior author, highlighted its adaptability for detecting and characterizing multiple pathogens that pose significant health risks. “By allowing us to refit the specifics of the CRISPR-based detection machinery, it can be relatively easily adopted to detect, quantify, and characterize multiple other pathogens,” Walt stated.
Wyss Founding Director Donald Ingber, M.D., Ph.D., praised the study as a testament to the power of collaboration and innovation in addressing pressing medical challenges. The convergence of cutting-edge technologies has yielded a solution with far-reaching implications for patient care and the healthcare system.
The research team, which includes Nayoung Kim, Emily Cotnoir, and Vishnu Chaturvedi, received funding from the Wyss Institute at Harvard University, Health Research Inc., the New York State Department of Health, and the Wadsworth Center Division of Infectious Diseases.
As the medical community continues to combat the threat of drug-resistant pathogens, the dSHERLOCK platform represents a significant step forward in diagnostic technology, offering hope for more effective management of infectious diseases.
