Sophie Culos

Topic

Determination of Leptospira Lipid A Diversity Across Distinct Environments

Department of Biochemistry and Microbiology

Date & location

• Tuesday, August 18, 2026
• 1:00 P.M.
• Clearihue Building, Room B017

Examining Committee

Supervisory Committee

• Dr. David Goodlett, Department of Biochemistry and Microbiology, University of Victoria (Co-Supervisor)
• Dr. Helena Petrosova, Department of Biochemistry and Microbiology, UVic (Co-Supervisor)
• Dr. Steve Perlman, Department of Biology, UVic (Outside Member)

External Examiner

• Dr. Stephen Tuffs, Department of Biochemistry and Microbiology, UVic

Chair of Oral Examination

• Dr. Erin Kelly, Department of English, UVic

Abstract

Pathogenic Leptospira are the causative agents of leptospirosis, an emerging zoonosis affecting humans, livestock, and wildlife across the globe. During infection, the host immune system engages with Leptospira lipopolysaccharide (LPS) and its constituents (O-antigen, oligosaccharide core, and lipid A). The structure and composition of LPS are central to pathogenic potential; modifications to LPS enable immune evasion, antimicrobial resistance, and host adaptation in many pathogens. Recent work has demonstrated that pathogenic L. interrogans cultured in host-like medium (EMEM) exhibits a lipid A phenotype resembling that observed in infected tissues, distinguishing it from the lipid A profile obtained from cultures grown in traditional media (EMJH). This study characterizes lipid A remodelling and differential protein expression profiles across Leptospira species in distinct environments.

This study characterized lipid A structures and proteomic profiles across pathogenic (P1+) and low virulence (P1-/P2) Leptospira species cultured in traditional and host-like conditions to identify lipid A modifications and biosynthetic pathways involved in virulence-associate adaptation. Representative Leptospira species were cultured in EMJH (30°C and 37°C, 5% CO₂) and EMEM (37°C, 5% CO₂). Lipid A was extracted using the Fast Lipid Analysis Technique (FLAT) and characterized with mass spectrometry. Whole-cell proteomics identified differentially expressed proteins across conditions.

All screened pathogenic (P1+) species followed the pattern of lipid A modification previously observed in L. interrogans, incorporating longer fatty acyl chains into lipid A in EMEM and producing penta-acylated lipid A. P1-/P2 species retained shorter acyl chains and did not produce penta-acylated lipid A, indicating subclade-specific lipid A remodelling. Proteomic analysis revealed largely constitutive expression of lipid A biosynthesis enzymes. P1+ species activated multi-pathway responses (heat shock, oxidoreductases, and motility) in EMEM, whereas P1-/P2 species exhibited a limited proteomic response. Lipid A remodeling in host-like environments represents a potential mechanism distinguishing pathogenic from “mild” Leptospira species.

This study provides insight into LPS-specific modifications and pathways in pathogenic Leptospira species, advancing our understanding of LPS-mediated environmental adaptation and underlying mechanisms of virulence.