Department of Molecular Microbiology

The Department of Molecular Microbiology teaches introductory courses in microbiology and pathogenic microorganisms for first-year medical students and graduate students. In conjunction with the Division of Biology & Biomedical Sciences (DBBS) program in Molecular Microbiology and Microbial Pathogenesis, the department also offers a number of advanced courses that are primarily designed for graduate students but also open to medical students. Advanced elective research activities are offered by faculty in the department.

Website:	http://www.microbiology.wustl.edu

Visit our website for more information about our faculty and their appointments.

Molecular Biology Research Electives

During the fourth year, opportunities exist for many varieties of advanced clinical or research experiences.

Molecular genetics of protozoan parasites and tropical diseases; biosynthesis of the parasite surface, genomics, virulence and drug action or resistance.

Molecular genetics and pathogenicity of the streptococci and other pathogenic gram-positive bacteria.

The Doering lab studies the opportunistic fungal pathogen Cryptococcus neoformans, with the dual motivations of elucidating basic biology and identifying potential drug targets. Projects include studies of the synthesis and regulation of the main cryptococcal virulence factor, its polysaccharide capsule, and host-fungal interactions. Current approaches include those of biochemistry, cell and molecular biology, and genetics; studies also include high-throughput analysis of host-pathogen interactions and computational approaches to reconstructing the capsule regulatory network.

Biochemistry of malaria.

RNA virus evolution; molecular biology of alphaviruses; alphavirus gene expression vectors; antiviral drug design.

Our focus is on the pathogenic mechanisms and disease outcomes in the urinary tract. Work in the Hultgren lab blends multiple scientific disciplines to elucidate bacterial and host mechanisms that determine the onset, course and outcome of interactions between a host mucosal surface and bacterial pathogens. Using genetics, genomics, biochemistry, structural biology, high-resolution imaging, animal models, clinical studies and combinatorial chemistry, we have illuminated new ways in which intracellular lifestyles and community behavior play critical roles in the pathogenesis of urinary tract infection. We have uncovered new principles of adhesive pili biogenesis in gram-negative bacteria by the chaperone/usher pathway, delineating the fine molecular details of a donor strand complementation and exchange mechanism by which the energy of final subunit folding is used to complete the assembly and extrusion of pili across the outer membrane. We revealed how uropathogenic Escherichia coli use type 1 pili to invade and establish biofilm-like intracellular bacterial communities within bladder cells as part of a mechanism that subverts host defenses and how quiescent intracellular reservoirs can seed recurrent infections. We have uncovered complex networks that govern mucosal epithelial response to infection, which we have shown determines disease outcome. Further, we have made seminal contributions to our understanding of the pathogenesis and response to other uropathogens, polymicrobial infections and catheter-associated UTIs and to the mechanisms by which bacteria form a directed amyloid fiber, curli, which is important in biofilm formation. Together, this work is changing the way UTIs are evaluated, reshaping models of bacterial infections in general and spawning new technologies to design novel vaccines and antimicrobial therapeutics to diagnose, treat and/or prevent UTIs and their sequelae.

The focus of this lab is polymicrobial infection and women's health. Our lab is using biochemical, cellular and animal models to study infectious processes of the female urogenital tract that involve multiple bacterial species. For example, bacterial vaginosis (BV) is a polymicrobial imbalance of the vaginal flora characterized by reductions in beneficial lactobacilli and an overgrowth of mostly gram-negative bacteria. BV is the most common of all vaginal infections, and it is associated with increased risks of adverse pregnancy outcomes and greater susceptibility to sexually transmitted infections. We are collaborating with clinical investigators to define molecular and biochemical processes of BV and to identify patient groups most at risk for adverse events. Another active area of study in the lab involves polymicrobial UTI. We have developed a mouse model of polymicrobial UTI and are currently defining novel processes, bacterial factors and host factors that contribute to susceptibility.

Our focus is antifungal therapy and vaccine development against a fungal pathogen: Cryptococcus neoformans. This is a significant fungal pathogen, particularly in immunocompromised patients, that causes pulmonary infections and meningoencephalitis. It has been estimated that more than 1,000,000 new cases of Cryptococcus infection occur annually, resulting in more than 650,000 deaths per year, primarily in Africa. Our lab focuses on understanding the structure and synthesis of the fungal cell wall. We are working on it as a target for antifungal therapies and for vaccine development.

We study the intracellular survival mechanisms of protozoan parasites, focusing on the model parasite Toxoplasma gondii. Current approaches include high-resolution microscopy, genetic mapping of virulence traits, comparative genomic analyses, and the development of animal models for studying pathogenesis and resistance.

Our main focus is the molecular pathogenesis of mycobacteria. Our laboratory integrates in vivo disease modeling, molecular biology and biochemistry to provide answers to the fundamental biological questions regarding molecular pathogenesis and to yield therapeutic strategies for the treatment of mycobacterial infections.

This lab's focus is on the structural and mechanistic studies of malaria pathogenesis. Our lab is interested in the molecular events that occur during erythrocyte invasion by Plasmodium parasites. We use the tools of structural biology, biochemistry and biophysics to examine proteins and protein complexes associated with these events.

Legionella pneumophila, the causative agent of Legionnaires' pneumonia, replicates inside alveolar macrophages by preventing phagosome-lysosome fusion.

Our work focuses on the discovery and characterization of novel viruses. We use functional genomic technologies to identify novel viruses from a variety of clinical samples from diseases of unexplained etiology. We then use epidemiologic, molecular and cellular strategies to define the relevance of newly identified viruses to human disease. A range of new viruses — including polyomaviruses, astroviruses and picronaviruses — are currently under investigation.

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Visit online course listings to view offerings for M30 MolMB.

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