Meta J. Kuehn

Associate Professor of Biochemistry

Biochemical and genetic analysis of secretory vesicles from pathogenic bacteria.

Contact Information

Office Number: (919) 684-2545

Fax: (919) 684-8885

e-mail mkuehn@biochem.duke.edu

Lab Location

Room 220B Nanaline Duke Building

Mailing Address

Department of Biochemistry

Nanaline H. Duke

Box 3711, DUMC

Durham, NC 27710

Education

• Ph.D. (Washington University, 1993)

Research Interests

Pathogenic bacteria use membrane vesicles as a means to secrete toxins and to contact host cells and tissues. The incorporation of different types of cellular material into vesicles is an outstanding system for studying both directed secretory pathways and mechanisms of bacterial virulence. Trainees in my lab biochemically evaluate vesicles produced by virulent human pathogens that contribute to a large proportion of worldwide cases of diarrhea and to disease in patients with cystic fibrosis: enterotoxigenic E. coli and Pseudomonas aeruginosa.

We are investigating the mechanism by which cellular material is brought to the sites of vesicle budding, the requirements for vesicle production, and the fate of the incorporated material in relation to the virulence of the parent organism. We are also identifying bacterial genes that influence the production of vesicles and have characterized members of an envelope stress pathway that regulate vesicle production. It is hoped that these studies will lead to the identification of therapeutic targets in these organisms. Since vesicle production is a ubiquitous process among gram-negative bacteria, the comparison of vesicle secretion in different organisms may reveal conserved general secretory mechanisms employed by many different gram-negative pathogens.

Recent Publications

1. A.J. McBroom and M.J. Kuehn (2007) “Release of outer membrane vesicles by gram-negative bacteria is a novel envelope stress response.” Mol Microbiol. 63:545-58.
2. A.J. McBroom, A.P. Johnson, S. Vemulapalli, and M.J. Kuehn (2006) “Outer membrane vesicle production by Escherichia coli is independent of membrane instability.” J Bacteriol. 188:5385-92
3. S.J. Bauman and M.J. Kuehn (2006) “Purification of outer membrane vesicles from Pseudomonas aeruginosa and their activation of an IL-8 response.” Microbes Infect. 8:2400-8.
4. M.J. Kuehn and N.C. Kesty (2005) “Bacterial outer membrane vesicles and the host-pathogen interaction.” Genes Dev. 19:2645-55.
5. A.J. McBroom and M.J. Kuehn (2005) “Chapt 2.2.4: Outer Membrane Vesicles in Eco-Sal.” (Roy Curtiss, III ed. in chief) ASM Press [Online].
6. N.C. Kesty, K.M. Mason, M. Reedy, S.E. Miller, and M.J. Kuehn (2004) “Host cell binding and internalization of enterotoxigenic E. coli vesicles via lipid rafts.” EMBO J. 23:4538-49.
7. N.C. Kesty and M.J. Kuehn (2004) “Incorporation of heterologous outer membrane and periplasmic proteins in E. coli outer membrane vesicles.” J Biol Chem. 279:2069-76.
8. A.L. Horstman, S.J. Bauman, and M.J. Kuehn (2004) “Lipopolysaccharide 3-deoxy-D-manno-octulosonic acid (Kdo) core determines bacterial association of secreted toxins.” J Biol Chem. 279:8070-5.
9. A.L. Horstman and M.J. Kuehn (2002) “Bacterial surface association of heat-labile enterotoxin through lipopolysaccharide after secretion via the general secretory pathway.” J Biol Chem. 277:32538-45.
10. A.L. Horstman and M.J. Kuehn (2000) “Enterotoxigenic Escherichia coli secretes active heat-labile enterotoxin via outer membrane vesicles” J Biol Chem. 275:12489-96.