- Louis Block Professor and Chair, Department of Microbiology
- Chair, Committee on Microbiology
Ph.D., The University of Cologne, 1988
M.D., The University of Cologne, 1988
The University of Chicago
920 East 58th Street
Chicago, Illinois 60637
Phone: (773) 834-9060
Our laboratory studies mechanisms whereby pathogenic bacteria cause human diseases in an effort to develop vaccines and therapeutics to combat these infections. Currently, we are focusing on MRSA (Staphylococcus aureus soft tissue and bloodstream infections), anthrax (Bacillus anthracis), and plague (Yersinia pestis). This work is conducted at the University of Chicago’s Hyde Park campus and at the Howard Taylor Ricketts Laboratory (Argonne National Laboratory), a facility for experimental work in high containment.
Our work has uncovered the mechanisms whereby surface proteins of Gram-positive bacteria are secreted, anchored to the cell wall or assembled into fimbrial structures, and released from the bacterial envelope (1). In S. aureus, this has led to the characterization of key virulence factors - staphylococcal protein A (SpA) and adenosine synthase (AdsA) - that block innate and adaptive immune responses in infected hosts by capturing Fcγ of immunoglobulin (2), crosslink B cell receptors to promote superantigen activity (3), inhibit immune responses with adenosine signaling (4) and promote macrophage cell death via deoxyadenosine synthesis (5). These insights have led to the development of vaccines (6), antibodies and therapeutics that prevent disease (7), improve the outcome of S. aureus infections or induce immunity (2, 8). Our future work will unravel the molecular mechanisms of S. aureus immune evasion and protein traffic across the bacterial envelope to discover new therapeutics and vaccines (9).
Bacillus anthracis assembles its S-layer and poly-γ-D-glutamic acid (PDGA) capsule to control the chain length of its vegetative forms and to prevent phagocytic clearance of the pathogen in mammalian hosts (1). S-layers are constituted from two S-layer proteins - Sap and EA1 - that require specific secretion and assembly factors to form a two-dimensional crystalline array on the bacterial surface, tethered via SLH domains to the secondary cell wall polysaccharide (SCWP) of peptidoglycan (10, 11). Twenty-two S-layer associated proteins - BSLs - fulfill discrete biological roles during vegetative replication, whereas linear PDGA strands traverse the S-layer and block phagocyte uptake (12, 13). Our current work characterizes the genes and mechanisms involved in SCWP and PDGA synthesis and the biological functions of S-layer and BSLs in promoting vegetative growth (14, 15). These insights are translated into the development of therapeutics against B. anthracis and into the design of protective vaccines (16, 17).
Yersinia pestis colonizes the gastrointestinal tract of fleas to support transmission of bacteria into mammalian hosts and then uses a type III secretion system and its effector proteins to kill host immune cells (18, 19). We are studying Y. pestis genes and the molecular biology that supports this complex life-style to determine the causes of pandemic plague outbreaks and to develop vaccines that can prevent outbreaks and spread of this catastrophic disease (20, 21).