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Central to the pathogenesis of
the bacterial pathogen Salmonella typhimurium is its ability to engage the host cell
in a two-way biochemical interaction through the function of a dedicated protein
secretion system termed type III. This system directs the translocation of several
bacterial effector proteins into the host cell resulting in the stimulation of a
variety of responses through the activation of small molecular weight GTP-binding
proteins of the Rho subfamily. These response are characterized by profuse actin-cytoskeleton
rearrangements and nuclear responses leading to bacterial uptake into host cells
and the production of pro-inflammatory cytokines. Our laboratory is interested in
understanding the mechanisms of the type III protein translocation system, the function
of the bacterial effector proteins that are translocated into the host cell as well
as the signal transduction pathways stimulated by these bacterial effectors that
lead to host cell responses.
Selected References
Marlovits TC, Kubori T, Lara-Tejero M, Thomas D, Unger VM, Galan JE. (2006). Assembly of the inner rod determines needle length in the type III secretion injectisome. Nature 441: 637-640.
Lara-Tejero M, Sutterwala FS, Ogura Y, Grant EP, Bertin J, Coyle AJ, Flavell RA, Galan JE. (2006). Role of the caspase-1 inflammasome in Salmonella typhimurium pathogenesis. J Exp Med. 203: 1407-1412.
Akeda Y, Galan JE. (2005). Chaperone release and unfolding of substrates in type III secretion. Nature 437: 911-915.
Marlovits TC, Kubori T, Sukhan A, Thomas DR, Galan JE, Unger VM. (2004). Structural insights into the assembly of the type III secretion needle complex. Science 306: 1040-1042.
Hernandez LD, Hueffer K, Wenk MR, Galan JE. (2004). Salmonella modulates vesicular traffic by altering phosphoinositide metabolism. Science 304: 1805-1807.
Haghjoo E, Galan JE. (2004). Salmonella typhi encodes a functional cytolethal distending toxin that is delivered into host cells by a bacterial-internalization pathway. Proc Natl Acad Sci U S A 101: 4614-4619.
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