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Faculty Detail     Name MICHAEL E. NIEDERWEIS   Campus Address BBRB 609 Zip 2170 Phone 205-996-2711 E-mail mnieder@uab.edu Other websites PubMed Listing

Faculty Appointment(s) Appointment Type Department Division Rank Primary  Microbiology  Microbiology Professor Center  Center for AIDS Research  Center for AIDS Research Professor

Graduate Biomedical Sciences Affiliations Biochemistry and Structural Biology  Cellular and Molecular Biology Program  Immunology  Medical Scientist Training Program  Microbiology

Biographical Sketch  Michael Niederweis (b. 1964), Professor of Microbiology, received a diploma in chemistry from the Saarland University, Germany, in 1989, and a Ph.D. in microbiology from the University of Erlangen-Nuernberg, Germany, in 1993. His graduate studies were with Dr. Wolfgang Hillen on the structural analysis of protein-DNA interactions. From 1994-1996, Dr. Niederweis did postdoctoral studies with Dr. Donald Crothers at the Yale University, New Haven, Dr. Lee W. Riley at the Cornell University, Medical College, New York, and Dr. Roland Benz, University of Wuerzburg. In 1997, he established his laboratory in the Microbiology Department of the University of Erlangen-Nuernberg, Germany, to study mycobacterial porins. He obtained multiple young investigator awards. Dr. Niederweis joined the UAB faculty in 2004.

Research/Clinical Interest Title Novel proteins in the outer membrane of mycobacteria: Functions, structures, role in tuberculosis and applications Description Tuberculosis is caused by Mycobacterium tuberculosis and kills approximately two million people each year, more than any other bacterial pathogen. Yet, M. tuberculosis is one of the least understood bacterial pathogens. Virulence of M. tuberculosis is mainly associated with its ability to survive within macrophages. The outer membrane is an efficient permeability barrier for toxic molecules and plays a key role in protecting M. tuberculosis from the host immune system. To date, the molecular basis for the transport of most solutes across the outer membrane is unknown for M. tuberculosis. The aim of our research is to identify and characterize the outer membrane proteome of M. tuberculosis. The identification of proteins that enable transport of solutes across the outer membrane would represent a major breakthrough in our understanding of the physiology and drug resistance of M. tuberculosis. The proteins which functionalize the outer membrane of M. tuberculosis are fascinating for several reasons: (i) They fulfill essential biological functions. (ii) The outer membrane proteins reside in a highly unusual lipid membrane. Therefore, their structures will be novel as we have already shown for MspA. This makes it likely that they also function by novel mechanisms. iii) Some outer membrane proteins are likely to represent attractive drug targets because inhibitors do not have to cross the notoriously impermeable outer membrane, which is a major determinant of the intrinsic drug resistance of M. tuberculosis. (iv) Many outer membrane proteins of pathogenic Gram-negative bacteria are involved in interactions with host cells. We assume that this will also be the case for M. tuberculosis.

Selected Publications  Publication PUBMEDID Copper resistance is essential for virulence of Mycobacterium tuberculosis  21205886  Mycobacterial outer membranes: in search of proteins  20060722  The growth rate of Mycobacterium smegmatis depends on sufficient porin-mediated influx of nutrients  16238622  Multidrug resistance of a porin deletion mutant of Mycobacterium smegmatis  15504836  The structure of a mycobacterial outer-membrane channel  14976314  Mycobacterial porins--new channel proteins in unique outer membranes  12940978  Porins in the cell wall of Mycobacterium tuberculosis  10515949

Keywords tuberculosis, virulence, antibiotic resistance, membrane, proteins, transport, nanotechnology

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