ASU SoLS Faculty: Rajeev Misra

Dr. Misra joined the Microbiology faculty at ASU in 1991 after receiving his postdoctoral training from Princeton University , New Jersey and Ph.D. degree from Adelaide University , Australia . Dr. Misra's laboratory studies bacterial outer membrane-associated events including transport of toxins, efflux of antibiotics, and targeting and assembly of outer membrane proteins (OMPs). These biological processes are being studied through utilizing genetic, molecular and biochemical approaches.

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 OMP involved in expelling antibiotics from inside the bacterial cell. However, TolC does not carry out such an efflux function alone; it interacts with AcrA and AcrB proteins 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.

Assembly of Outer Membrane Proteins in E . coli . The second major research interest of our laboratory entails the fundamental biological event of protein targeting and assembly. All proteins must reach their pre-determined cellular locations in a correctly folded conformation in order to be functionally active. We are studying how E . coli OMPs reach their destination. The uniquely structured and multifunctional TolC protein as well as OmpF and LamB, the channel-forming beta-barrel OMPs, have been used as models. In particular, we are interested in (1) elucidating OMP assembly pathways and examining the roles of YaeT and YfgL in OMP assembly, and (2) cellular responses to stress signals that are activated when OMP assembly is compromised.

Publications (2003-2007):

Masi, M., P. Vuong, M. Humbard, K. Malone, and R. Misra. 2007. Initial steps of colicin E1 import across the outer membrane of Escherichia coli . J. Bacteriol. 189:2667-2676.

Misra, R. 2007. First glimpse of the crystal structure of YaeT's POTRA domains. Chem. Biol. In press .

Vuong, P., J. Mantei, D. Bennion, D. Frost, and R. Misra. 2007. Analysis of YfgL and YaeT interactions through bioinformatics, mutagenesis, and biochemistry. J. Bacteriol. (Under revision).

Charlson, S. E., J. N. Werner, and R. Misra. 2006. Differential effects of yfgL mutation on the biogenesis of Escherichia coli outer membrane proteins and lipopolysaccharide. J. Bacteriol. 188:7186-7194.

Malinverni, J. C., J. Werner, S. Kim, J. G. Sklar, D. Kahne, R. Misra, and T. J. Silhavy. 2006. YfiO stabilizes the YaeT complex and is essential for outer membrane protein assembly in E . coli . Mol. Microbiol. 61:151-164.

German, G. J., R. Misra, and A. Kropinski. 2006. The T1-like bacteriophages. p 211-224. In The Bacteriophages. R. Calender (ed). Oxford University Press . New York , NY .

Castillo-Keller M, Vuang P, Misra R. 2006. Novel mechanism of porin expression regulation. J. Bacteriol. 188:576-586.

Werner J, Misra R. 2005. YaeT (Omp85) affects the assembly of lipid-dependent and lipid-independent outer membrane proteins of Escherichia coli. Mol Microbiol. 57(5):1450-9.

Husain F, Humbard M, Misra R. 2004. Interaction between the TolC and AcrA proteins of a multidrug efflux system of Escherichia coli. J Bacteriol. 186(24):8533-6.

Gerken H, Misra R. 2004. Genetic evidence for functional interactions between TolC and AcrA proteins of a major antibiotic efflux pump of Escherichia coli. Mol Microbiol. 54(3):620-31.

Augustus AM, Celaya T, Husain F, Humbard M, Misra R. 2004. Antibiotic-sensitive TolC mutants and their suppressors. J Bacteriol. 186(6):1851-60.

Castillo Keller, M., and R. Misra. 2003. Protease-deficient DegP suppresses lethal effects of a mutant OmpC protein by its capture. J. Bacteriol. 185:148-154.

Werner, J., A. M. Augustus, and R. Misra. 2003. Assembly of TolC, a structurally unique and multifunctional outer membrane protein of Escherichia coli K-12. J. Bacteriol. 185:6540-6547.