Beyond Culture: Direct Lipidomic Pathogen Identification for Rapid Clinical Mass Spectrometry

Robert K Ernst
University of Maryland - Baltimore, Baltimore, MD

Robert Ernst, PhD (Presenter) University of Maryland - Baltimore

Presenter Bio: Robert (Bob) K. Ernst, Ph.D., is the Dr. Paul and Mrs. Jean Corcoran Endowed Professor and Chair of the Department of Microbial Pathogenesis in the School of Dentistry and an Adjunct Professor in the School of Medicine. He is also a University of Maryland, Baltimore Distinguished University Professor. He earned his undergraduate degree in Biology at the State University of New York at Oswego and his PhD in Microbiology at the University of Virginia in the laboratories of Dr. David Rekosh and Dr. Marie Louise Hammarskjold. His post-doctoral research work in Dr. Samuel Miller’s laboratory at the University of Washington focused on understanding the role of bacterial membrane lipids, specifically lipopolysaccharide in altering and defending against host innate immune recognition and killing mechanisms. Prior to joining the Department of Microbial Pathogenesis in 2008, he was a Research Associate Professor in the Department of Medicine, Division of Allergy and Infectious Diseases at the University of Washington.

Dr. Ernst’s laboratory has been at the forefront of innovative research studying the molecular basis and adaptive significance of modifications to the structure of lipopolysaccharide (LPS). He specifically focuses on the elucidation of the molecular basis by which Gram-negative bacteria modify the lipid A component of lipopolysaccharide (LPS) and how these alterations affect or circumvent normal host innate immune system responses. He has also developed a practical method, bacterial enzymatic combinatorial chemistry (BECC) that can be used to engineer functionally diverse lipid A molecules for use as vaccine adjuvant and for the rapid identification of pathogens directly from complex biological fluids, such as blood and urine, without the need for ex vivo amplification using mass spectrometry.

Relevant Financial Disclosures (within past 24 months, reported on Jul 07, 2026) Honorarium/Expenses Reviewer - Cystic Fibrosis Foundation, Invited Speaker - University of Pittsburgh, CanMetCon, Duke University, Cystic Fibrosis Foundation Vermont meeting Consultant Fees N/A Grant/Research Support NIH, Cystic Fibrosis Foundation Committee/Board/Advisory Board Chair of the scientific advisory board TollerBio Stock/Bonds N/A Salary UMB Ownership Interest Pataigin (www.pataigin.com) and TollereBio (www.tollerebio.com) Royalty / IP / Other Income N/A Other Potential Conflicts N/A Discussing Products? NO, presenter will NOT present educational content related to products/services of the ineligible company(ies) listed above. Conflict mitigation NOT REQUIRED.

Rapid identification of pathogens remains a major challenge in clinical microbiology, particularly in high-acuity infections where timely intervention is critical. Although culture-based workflows and protein-based MALDI-TOF platforms have improved diagnostics, they still depend on prior culture and remain limited in direct-from-specimen analysis and polymicrobial detection. Using FLAT (Fast Lipid Analysis Technique), a culture-independent lipidomics platform, we leverage microbial membrane lipid signatures as species-specific chemical fingerprints to directly identify bacteria and fungi from complex clinical specimens, including blood cultures, urine, cerebrospinal fluid, and fecal samples, in under one hour. By moving beyond protein fingerprints and into lipid structure, FLAT offers a faster, more informative, and operationally practical approach to microbial diagnostics.

We have also advanced the FLAT platform through FLOAT (Fast Lipid O-Antigen Typing), FLATn-IMS, and library-assisted structural analysis. Together, these approaches enable O-antigen serotyping, core oligosaccharide profiling, lipid A characterization, and ion mobility-enhanced analysis of complex biological samples, including matrices in which microbial lipid signatures must be distinguished from host- and diet-derived background lipids.

More broadly, this work advances mass spectrometry from culture-dependent confirmation to direct chemical interrogation of real-world microbial specimens, creating a framework for direct, culture-independent pathogen identification and structural phenotyping on FDA-cleared instruments already available in clinical laboratories.