Harvard Medical School


Contact Information:

Dept. of Microbiology and
Immunobiology

Harvard Medical School

NRB, Room 1035A

77 Avenue Louis Pasteur

Boston, MA 02115

phone: 617-432-1935

fax: 617-738-7664

 

jmekalanos@hms.harvard.edu

Mekalanos Lab Home

 

Research Summary

The Mekalanos laboratory is primarily engaged in the biochemical and genetic analysis of bacterial virulence factors. The long-term goal of these studies is to understand how pathogenic bacteria evade the host immune system and ultimately cause disease. While a variety of organisms are currently being studied in the laboratory (e.g. Helicobacter pylori, Pseudomonas aeruginosa, Haemophilus influenzae, and E. coli) the longest ongoing research project concerns the bacterium Vibrio cholerae. This organism produces an adenylate cyclase-activating toxin which has effects on the physiology of the intestine and enhances the colonization of the intestine. While cholera toxin is the most-studied virulence factor, strains lacking cholera toxin still cause symptoms. Recent work has identified a novel toxin that may be partly responsible for this; the mechanism by which this occurs is currently under investigation.

The Mekalanos lab has recently developed a variety of new genetic strategies for identifying genes required for survival of bacteria in vitro and in vivo. Some of these genes have turned out to be essential for infection and/or virulence. Understanding the molecular mechanism of how these gene products are regulated in vivo and the role that these regulatory responses play in pathogenesis are long term goals of the laboratory. Where possible, the knowledge gained in these studies will be applied to the development of more effective vaccines for bacterial diseases and the identification of new targets for antimicrobial drug development. We have also discovered novel toxins and protein secretion systems that may be partly responsible for virulence in vivo which are currently under investigation.

Selected Publications

Tam VC, Serruto D, Dziejman M, Brieher W, Mekalanos JJ.
A type III secretion system in Vibrio cholerae translocates a formin/spire hybrid-like actin nucleator to promote intestinal colonization.
Cell Host Microbe. 2007 Apr 19;1(2):95-107. PubMed

Pukatzki S, Ma AT, Revel AT, Sturtevant D, Mekalanos JJ.
Type VI secretion system translocates a phage tail spike-like protein into target cells where it cross-links actin.
Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15508-13. PubMed

Shakhnovich EA, Hung DT, Pierson E, Lee K, Mekalanos JJ.
Virstatin inhibits dimerization of the transcriptional activator ToxT.
Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2372-7. PubMed

Mougous JD, Cuff ME, Raunser S, Shen A, Zhou M, Gifford CA, Goodman AL, Joachimiak G, Ordoñez CL, Lory S, Walz T, Joachimiak A, Mekalanos JJ.
A virulence locus of Pseudomonas aeruginosa encodes a protein secretion apparatus.
Science. 2006 Jun 9;312(5779):1526-30. PubMed

Pukatzki S, Ma AT, Sturtevant D, Krastins B, Sarracino D, Nelson WC, Heidelberg JF, Mekalanos JJ.
Identification of a conserved bacterial protein secretion system in Vibrio cholerae using the Dictyostelium host model system.
Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1528-33. PubMed

Hung DT, Shakhnovich EA, Pierson E, Mekalanos JJ.
Small-molecule inhibitor of Vibrio cholerae virulence and intestinal
colonization.
Science. 2005 Oct 28;310(5748):670-4. PubMed