Dept. of Microbiology and Immunobiology
Harvard Medical School
NRB, Room 1038A
77 Avenue Louis Pasteur
Boston, MA 02115
Click here to visit the Lory Lab Website.
The major research efforts in the laboratory are directed towards understanding the molecular basis of pathogenesis of human infections caused by opportunistic gram-negative bacteria. The projects aim to better understand the molecular basis of regulation of expression of determinants of pathogenicity by the microorganisms, starting from signal perception and transmission, regulation of gene expression at the transcriptional and post-transcriptional levels and the targeting mechanisms of the virulence factors to their site of action. We have used Pseudomonas aeruginosa as a model opportunistic pathogen, because of its importance in infections of individuals with cystic fibrosis, patients with neutropenia, or those with serious burns and wounds. In each of these environments, the unique host-parasite relationship allows us to examination of a variety of bacterial factors that lead to colonization, persistence and resistance to host defenses.
Another area of research in the laboratory focuses on studying the evolution of virulence traits in P. aeruginosa. We have identified several mobile elements, arranged in blocks of genes (so called genomic islands) that can move between bacteria, resulting in re-shaping of the genetic repertoire of individual recipient strains. The mechanisms and the consequences of this type of horizontal gene transfer, particularly if it leads to the acquisition of new virulence traits, will be analyzed in several infection models.
Kulasekara, H., Lee V, Brencic, A., Urbach, J., Miyata, S., Lee, D.G., Neely, A.N., Hayakawa, Y., Ausubel, F.M., and Lory, S. (2006). Systematic analysis of Pseudomonas aeruginosa proteins with diguanylate cyclase and phosphodiesterase domains reveals a role for cyclic di-GMP in virulence. Proc. Natl. Acad. Sci. USA. USA. 103: 2839-2844.
Kulasekara, BR Kulasekara, H.D., Wolfgang, M. C., Stevens, L., Frank D.W, and Lory, S. (2006). Acquisition and evolution of the exoU locus in Pseudomonas aeruginosa. J. Bacteriol. 188:4037-50.
Mougous, J.D., Cuff, M.E., Raunser S., Shen A., Zhou M., Gifford C.A., Goodman A.L., Joachimiak G., Ordonez C.L., Lory S., Walz .T, Joachimiak A., and Mekalanos J.J. (2006). A virulence locus of Pseudomonas aeruginosa encodes a protein secretion apparatus. Science. 312:1526-30.
Qiu, X. Gurkar, A.U. and Lory, S. (2006) Inter-strain transfer of the large pathogenicity island (PAPI-1) of Pseudomonas aeruginosa . Proc. Natl. Acad. Sci. USA. 103:19830-5.
Merighi M., Lee V.T., Hyodo M., Hayakawa Y. and Lory S. (2007) The second messenger bis-(3’-5’)-cyclic-GMP and its PilZ domain-containing receptor Alg44 are required for alginate biosynthesis in Pseudomonas aeruginosa . Mol. Microbiol 65:876-9.
Lee V.T, Matewish J.M., Kessler J.L., Hyodo M., Hayakawa Y., and Lory S. (2007) A cyclic-di-GMP receptor required for bacterial exopolysaccharide production. Mol. Microbiol 65:1474-84.
Arnoldo A., Curak J., Kittanakom S., Chevelev I., Lee V.T., Sahebol-Amri M., Koscik B., Ljuma L., Roy P. J., Bedalov A., Nislow C., Merrill R., Lory S., Stagljar I. (2008) Identification of small molecule inhibitors of Pseudomonas aeruginosa Exotoxin S using a yeast phenotypic screen. PLoS Genetics 29:4 e1000005)
Mathee K., Narasimhan G., Qiu X., Camilo Valdes C., Matewish J.M., Koehrsen M., Rokas A., Yandava C.N., Engels R., Zeng E., Olavarietta R., Doud M., Smith R., Montgomery P., White J., Godfrey P.A., Kodira C., Birren B., Galagan J. and Lory S. (2008). Dynamics of Pseudomonas aeruginosa genome evolution. Proc. Natl. Acad. Sci. USA. USA. 105:3100-5.
Huang J., Lesser C., and Lory S (2008) The essential role of the CopNproteinfor Chlamydia pneumoniae intracellular growth. Nature. 456:112-5.
Goodman AL., Merighi M., M Hyodo M., Ventre I., Filloux A., and Lory S. (2009). Direct interaction between sensor kinase proteins mediates acute and chronic disease phenotypes in a bacterial pathogen Genes and Development 23:249-59.
Klepac-Ceraj V, Lemon K.P., Martin T.R, Allgaier M., Kembel S.W., Knapp A.A., Lory S., Brodie E.L., Lynch S.V., Bohannan B.J.M., Green J.L., Maurer B.A. and Kolter R.G. (2010). Relationship between cystic fibrosis respiratory tract bacterial communities and age, genotype, antibiotics and Pseudomonas aeruginosa. Environmental Microbiol. In press.