Lecture
Chemical strategies to understand bacterial immune evasion
- Date
- Tuesday 3 March 2026
- Time
- Location
-
Gorlaeus Building
Einsteinweg 55
2333 CC Leiden - Room
- CM.3.23
Abstract
Bacterial pathogens evade host immunity through secreted proteins and enzymes that act at the microbiota–immune interface. However, the precise functions of many of these factors during infection remain unclear. In this presentation, I will highlight recent, unpublished work from my group in which we use chemical biology approaches to dissect bacterial immune-evasion mechanisms.
First, I will discuss IgA1 proteases (IgA1Ps) from Haemophilus influenzae. IgA1Ps cleave human IgA1 antibodies and thereby disable a central effector of mucosal immune defense. This immune-evasion mechanism is particularly relevant in chronic obstructive pulmonary disease (COPD), where H. influenzae drives persistent airway colonization and acute exacerbations. Using substrate-mimicking activity-based probes equipped with serine-reactive warheads, we developed selective chemical tools that label active IgA1Ps in complex biological samples. Functional profiling across H. influenzae clinical isolates revealed pronounced heterogeneity in IgA1P activity, identifying strains with enhanced immune-evasive potential. Furthermore, competitive screening enabled the identification of inhibitors that block IgA1 cleavage and restore antibody binding at the bacterial surface. Ongoing work in my group extends this strategy to additional extracellular proteases involved in bacterial pathogenesis.
Second, I will present our work on bacterial inhibition of host lysosomal proteases.Cathepsins are essential for pathogen degradation and immune activation, yet the mechanisms by which bacteria modulate their activity remain poorly defined. Using competitive activity-based protein profiling combined with proteomic strategies, we aim to identify bacterial proteins that directly interact with and modulate host cathepsins. Our preliminary data suggest that direct targeting of host proteases may represent a broader immune-evasion strategy than previously appreciated.
Biosketch
Dr. Michaela Prothiwa is a tenure-track Assistant Professor at the University of Antwerp, where she established her independent research group in 2023. Working at the interface of chemical biology and microbiology, her group develops chemical tools to dissect immune–microbe interactions and uncover mechanisms that inform new anti-infective strategies.
Dr. Prothiwa received her Master’s degree in Pharmaceutical Sciences from Ludwig Maximilian University of Munich and conducted her thesis research at Harvard University in the laboratory of Prof. Alan Saghatelian. She earned her PhD at the University of Konstanz under the supervision of Prof. Thomas Böttcher, supported by a Carl Zeiss Foundation Fellowship, where she developed chemical probes to investigate virulence-associated enzymes in bacterial pathogens. She subsequently joined KU Leuven as a postdoctoral fellow in the laboratory of Prof. Steven Verhelst, supported by a fellowship from the German Research Foundation (DFG), where she focused on activity-based probes to profile proteases in mammalian immune cells.
In 2020, she received the German KlarText Prize for excellence in science communication. She is an elected member of the Flemish Young Academy.