Research Interests

Role of TolC in Antibiotic Efflux and Colicin Import. Harmful agents such as toxins and antibiotics present in nature, constantly challenge bacterial survival. In response to these challenges, bacterial cells have developed strategies that allow them to survive in the hostile environments in which they live. TolC is the key outer membrane protein involved in the expelling of antibiotics from inside the bacterial cell. However, TolC does not carry out such an efflux function alone; it interacts with proteins present in the inner membrane to establish a functional efflux conduit. Curiously, while helping bacteria to survive the antibiotic assault, it has been exploited by a bacterial toxin, colicin E1, to gain entry into the cell and kill bacteria that do not secrete this toxin. The involvement of TolC in secreting virulence factors makes it an important protein in bacterial pathogenesis. Studies are being conducted to (1) dissect the role of TolC residues in antibiotic efflux and colicin import, and (2) reveal various protein-protein interactions that must occur to achieve these transport activities.

Relevant literature from Misra Lab:

Husain F, Humbard M, Misra R. Interactions Between the TolC and AcrA Proteins of a Multidrug Efflux System of Escherichia coli. Submitted.

Gerken, H. and R. Misra. Genetic Evidence for AcrB-dependent functional interactions between TolC and AcrA proteins of a major antibiotic efflux pump of Escherichia coli. Submitted.

Augustus AM, Celaya T, Husain F, Humbard M, Misra R. Antibiotic-Sensitive TolC Mutants and Their Suppressors. J Bacteriol. 2004 Mar;186(6):1851-60. [ABSTRACT] [PDF]

Relevant literature from other labs:

Nehme D, Li XZ, Elliot R, Poole K. Assembly of the MexAB-OprM Multidrug Efflux System of Pseudomonas aeruginosa: Identification and Characterization of Mutations in mexA Compromising MexA Multimerization and Interaction with MexB. J Bacteriol. 2004 May;186(10):2973-83.

Nikaido H. Molecular basis of bacterial outer membrane permeability revisited. Microbiol Mol Biol Rev. 2003 Dec;67(4):593-656.

Murakami S, Nakashima R, Yamashita E, Yamaguchi A. Crystal structure of bacterial multidrug efflux transporter AcrB. Nature. 2002 Oct 10;419(6907):587-93.