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Case Western Reserve University

MOLECULAR BIOLOGY
and MICROBIOLOGY

 
 
       
 

 

Arne Rietsch


Assistant Professor

Bacterial Pathogenesis

Office Phone: 216-368-2249
Office Fax: 216.368.3055
email: arne.rietsch@case.edu


     
 

My laboratory studies how the bacterial pathogen Pseudomonas aeruginosa causes disease. In particular, we are focusing on the type III secretion system that allows P. aeruginosa to deliver protein toxins directly into the cytoplasm of targeted host cells. Secretion is triggered by cell contact. This mode of intoxication is therefore often referred to as contact-dependent secretion.

Our interest in type III secretion centers on triggering of effector secretion by cell contact. We are currently focusing on three aspects of this process.

  • Translocator protein secretion: We have discovered that translocator proteins are secreted prior to cell contact at a point in time when effector secretion is off. Current efforts are directed at identifying the translocator signals that direct their export prior to cell contact, as well as the apparatus components that parse these signals.
  • Effector secretion is actively prevented prior to cell contact by two sets of proteins PcrG/PcrV and the PopN complex. We recently presented evidence that PcrV controls effector secretion allosterically by assembling at the needle tip and switching the apparatus to the effector secretion ‘off’ conformation. We are currently engaged in defining the role of PcrG (which is cytoplasmic) in this process, as well as integrating control by the PopN complex into our model.
  • The mechanism by which cell-contact triggers effector secretion is poorly understood. We have discovered that translocation of effector proteins into certain host-cells is feedback inhibited by the action of the type III effector ExoS. This feedback inhibition specifically affects triggering of effector secretion, not insertion of the translocon. Experiments are underway to probe the structure of the translocon, with the long-range goal of identifying the cue that triggers effector secretion and how this signal is perceived by the T3SS.

type III secretion gene induction

Figure legend: Triggering of effector secretion on cell contact. The type III secretion apparatus is assembled prior to cell contact and exports the pore-forming translocator proteins PopB and PopD. Upon cell contact the translocator proteins are inserted into the host cell membrane, forming a pore, which is docked to the needle-tip composed of PcrV (green, pore + needle-tip = translocon). Once the appropriate cue has been received, effector secretion is triggered. One of the effector proteins, ExoS, can down-regulate the signal for effector secretion. Export of effectors prior to cell-contact is prevented by the PopN complex (PopN (N), Pcr1 (1), Pcr2 (2) and PscB (B)), as well as PcrG (G) and PcrV. It is thought that triggering of effector secretion results in a conformational change in the needle-tip that is propagated down the needle to the base of the apparatus, resulting in effector export (indicated by the change in coloring/shape of the apparatus).

Selected Publications

Cisz, M., Lee, P.C. and Rietsch, A. (2008) ExoS controls the cell contact-mediated switch to effector secretion in Pseudomonas aeruginosa. J. Bact. 190(8): 2726-38 [PubMed]

Rietsch A. and Mekalanos, J.J, (2006) Metabolic Regulation of Type III Secretion Gene Expression in Pseudomonas aeruginosa, Mol. Micro. 59(3):807-820. [PubMed]

Sun Y, Karmakar M, Taylor PR, Rietsch A, Pearlman E. (2012) J Immunol. ExoS and ExoT ADP ribosyltransferase activities mediate Pseudomonas aeruginosa keratitis by promoting neutrophil apoptosis and bacterial survival. 188(4):1884-95.

Sun Y, Karmakar M, Roy S, Ramadan RT, Williams SR, Howell S, Shive CL, Han Y, Stopford CM, Rietsch A, Pearlman E. (2010) TLR4 and TLR5 on corneal macrophages regulate Pseudomonas aeruginosa keratitis by signaling through MyD88-dependent and -independent pathways. J Immunol. 185(7):4272-83.

Lee PC, Stopford CM, Svenson AG, Rietsch A. (2010) Control of effector export by the Pseudomonas aeruginosa type III secretion proteins PcrG and PcrV. Mol Microbiol. 2010 Feb;75(4):924-41.

Complete list of Publications