Room: BLS 435
Room: BLS 440
Research & Interests
My laboratory conducts research on the interaction of the human pathogen Chlamydia trachomatis with the epithelium. The principal research question we are addressing is the mechanism by which Chlamydia subverts host cell signaling to hijack the host cytoskeleton and vesicular transport to facilitate infection and nutrient acquisition. We are Specific topics include the following:
I. Invasion of non-phagocytic cells
Chlamydia is an obligate intracellular pathogen. It absolutely requires an intracellular niche for its replication. It has evolved to hijack the actin remodeling machinery to induce its uptake by the non-phagocytic epithelial cells that line the ocular and the genital mucosae. We have identified a number of signaling pathways that engage the virulence factor TarP, which stands for translocated actin-recruiting protein. We are investigating how these multiple pathways interact to mediate an extremely efficient invasion process. In addition, we are exploring mechanisms that regulate the signaling function of TarP.
II. Modulation of host cell focal adhesions
The developmental cycle of Chlamydia involves the interconversion between the infectious, but metabolically limited form, the elementary body (EB), and the vegetative, but non-infectious reticulate body (RB). Chlamydia spends most of its developmental cycle in the non-infectious form, making it vulnerable to a number of anti-microbial strategies of epithelial cells. One of these is the self-induced extrusion from the epithelium to minimize dissemination along the tissue. Extrusion occurring prior to the formation of infectious elementary bodies is detrimental to the pathogen. Therefore, Chlamydia has evolved mechanisms to stabilize the adhesion of the host cell to the extracellular matrix. We are investigating chlamydial factors that mediate the inhibition of focal adhesion turnover and their mechanisms of action in the context of 2D and 3D cell culture systems.
III. Iron homeostasis in Chlamydia
The means of transcriptionally regulating genes involve in iron acquisition, storage, and metabolism has been well-elucidated in other bacterial species, but not in Chlamydia. Genome sequencing information hints that it acquires iron and regulate iron-dependent transcription differently than in other prokaryotes. We identified an iron-dependent transcriptional repressor that is genome-encoded as a fusion protein with a putative iron permease, and requires to be liberated from the permease subunit by proteolytic cleavage. We are currently characterizing the function of the repressor, and also identify if it represents the major iron-dependent regulatory mechanism in Chlamydia trachomatis.
- Thwaites TR, Pedrosa AT, Peacock TP, Carabeo RA (2015) Vinculin Interacts with the Chlamydia Effector TarP Via a Tripartite Vinculin Binding Domain to Mediate Actin Recruitment and Assembly at the Plasma Membrane Front Cell Infect Microbiol 5, 88
- Thwaites T.R., Nogueira A.T., Campeotto I., Silva A.P., Grieshaber S.S., and Carabeo R.A (2014) The Chlamydia effector TarP mimics the mammalian LD motif of paxillin to subvert the focal adhesion kinase during invasion J. Biol. Chem. 289, 30426-42
- Thompson C.C., Nicod S., Malcolm D., Grieshaber S.S., and Carabeo R.A. (2012) An iron-dependent transcriptional regulator is generated from cleavage of the YtgC permease in Chlamydia trachomatis Proc. Nat. Acad. Sci. U.S.A. 109, 10546-51
- Brinkworth, A.J., Malcolm, D.S., Pedrosa, A.T., Roguska, K., Shahbazian, S., Graham, J.E., Hayward, R.D., and Carabeo, R.A. (2011) Chlamydia trachomatis Slc1 is a type III secretion chaperone that enhances the translocation of its invasion effector substrate TARP Mol Microbiol. 82, 131-44
- Carabeo RA (2011) Bacterial subversion of host actin dynamics at the plasma membrane Cell Microbiol.
- Fields, K.A., Heinzen, R.A., and Carabeo, R. (2011) The obligate intracellular lifestyle Front Microbiol. 2, 99
- Thompson, C.C., and Carabeo, R.A. (2010) An optimal method of iron starvation of the obligate intracellular pathogen, Chlamydia trachomatis Front. Microbio. 2, 20
- Ouellette, S., Dorsey, F., Moshiach, S., Cleveland, J., and Carabeo, R.A. (2011) Chlamydia Species-Dependent Differences in the Growth Requirement for Lysosomes PLoS ONE
- Ouellette, S., and Carabeo, R.A. (2010) A Functional Slow Recycling Pathway of Transferrin is Essential for Chlamydial Intracellular Growth Front. Microbiol.
- Tietzel, I., El-Haibi, C., and Carabeo, R.A. (2009) The Human Guanylate Binding Proteins Potentiate the Anti-Chlamydial Effects of Interferon-g PLoS ONE 4(8)
- Lane, B.J., Mutchler, C, and Carabeo, R.A. (2008) Chlamydial Invasion Involves TARP binding of Two distinct Rac-specific Guanine Nucleotide Exchange Factors PLOS Pathogens 4
- Molmeret, M., Santic, M., Asare, R., Carabeo, R.A., Kwaik, Y.A. (2007) Rapid Escape of the dot/icm Mutants of Legionella pneumophila Into the Cytosol of Mammalian and Protozoan Cells Infect. Immun. 75, 3290-3304
- Carabeo, R.A., Dooley, C.A., Grieshaber, S.S., and Hackstadt, T (2007) Rac Interacts with Abi-1 and WAVE2 to Promote an Arp2/3-dependent Actin Recruitment During Chlamydial Invasion Cell. Microbiol. 9, 2278-2288
- Clifton, D.R., Dooley, C.A., Grieshaber, S.S., Fields, K.A., Carabeo, R.A., Hackstadt, T (2005) Tyrosine Phosphorylation of the Chlamydia Effector Protein Tarp is Species-Specific and Not Required for Recruitment of Actin. Infect. Immun. 73, 3860-3868
- Clifton, D.R., Fields, K.A., Grieshaber, S.S., Dooley, C.A., Fischer, E.R., Mead, D.J., Carabeo, R.A., Hackstadt, T (2004) A Chlamydial Type III Translocated Protein is Tyrosine Phosphorylated at the Site of Entry and Associated with Recruitment of Actin Proc. Nat. Acad. Sci. U.S.A. 101, 10166-10177
- Carabeo, R.A., Grieshaber, S.S., Dooley, C.A., Hasenkrug, A., and Hackstadt, T (2004) Requirement for the Rac GTPase in Chlamydia trachomatis Invasion of Non-phagocytic Cells Traffic 5, 418-425
- Carabeo, R.A., Mead, D.J., Hackstadt, T (2003) Golgi-dependent transport of cholesterol to the Chlamydia trachomatis inclusion Proc. Natl. Acad. Sci. USA. 100, 6771-6
- Carabeo, R.A., Grieshaber, S.S., Fischer, E., Hackstadt, T (2002) Chlamydia trachomatis induces remodeling of the actin cytoskeleton during attachment and entry into HeLa cells. Infect. Immun. 70:3793-803. Infect. Immun. 70, 3793-803
- Carabeo, R.A., Hackstadt, T (2001) Isolation and characterization of a mutant Chinese hamster ovary cell line that is resistant to Chlamydia trachomatis infection at a novel step in the attachment process Infect. Immun. 69, 5899-904