Michael Niederweis, Ph.D.
Professor
Department of Microbiology

Telephone: (205) 996-2711
Office Location: BBRB 609, zip 2170
Email: mnieder@uab.edu

Research Focus:  Novel proteins in the unique outer membrane of Mycobacterium tuberculosis: Functions, structures and role in virulence

Biography | Lab Research Focus | References on PubMed

Lab Research Focus

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.