Faculty- Nathalie Dautin

      Nathalie Dautin

   Assistant Professor

 

Room: McCort-Ward 105 Phone: 202-319-5278 Fax: 202-319-5721 e-mail: dautin@cua.edu

EDUCATION AND TRAINING:

            · B.S., Biochemistry, University Denis-Diderot, Paris, France.

            · M.S., Microbiology, University Denis-Diderot, Paris, France.

            · Ph.D, Microbiology, University Denis-Diderot, Paris, France.

            · Postdoctoral Research, National Institutes of Health, Bethesda, MD.

TEACHING INTERESTS:

            · General Microbiology

            · Microbial pathogenesis

RESEARCH INTERESTS:

Our laboratory is interested in understanding how pathogenic bacteria assemble and secrete virulence factors. Virulence factors are molecules produced by bacteria that participate in various aspect of bacterial pathogenesis: colonization of the host, evasion of host’s immune system, invasion of host cells, and inhibition of host’s cell function.

Despite their functional diversity, most virulence factors need to be localized outside the bacteria (either on the surface of bacteria, free in the extracellular medium, or in the host cell) in order to contact their target.  This implies that after synthesis in the bacterial cytoplasm, virulence factors need to be secreted through the bacteria membrane(s) to reach their final destination.

Proteins secretion mechanisms have been studied both in Gram-positive and Gram-negative bacteria. Gram-negative bacteria, in contrast with Gram-positive bacteria, possess two membranes: the inner and the outer membrane. Thus, Gram-negative bacteria have evolved secretion systems that are specifically adapted to deal with this “double membrane”, and are absent from Gram-positive bacteria.

Currently, six secretion systems have been identified in Gram-negative bacteria. Among those, the type 5 secretion system (T5SS) is by far the more widespread (more than 1000 proteins are predicted to use this pathway for secretion) and supposedly the simplest.

The T5SS comprises 4 sub-families: the T5SSa or “monomeric” autotransporters; the T5SSb, which include proteins secreted by the “two-partner secretion system” and the T5SSc, which comprises the “trimeric” autotransporters. Recently, the Intimin and Invasin family of proteins (Int/Inv) have been proposed to be “inverted” autotransporters and can thus be classified as T5SSd.

All protein secreted by the T5SS rely on a beta-barrel forming domain (b-domain or “translocator” domain) for secretion through the outer membrane. In autotransporters and Intimin/Invasin, this domain is produced as a fusion with the secreted domain (called “passenger domain”). In contrast, in the “two-partner secretion system” (T5SSb), the b-domain and the passenger domain are encoded by separate ORFs.

Although the b-domain is necessary for secretion of the passenger domain in the extracellular space, whether it is actually directly involved in its transport through the outer membrane is still a subject of controversy.

Our goal is to understand the mechanism of biogenesis and secretion of proteins belonging to the T5SS. We are focusing on the mechanisms and potential role of post-translational modifications of those proteins, and on the mechanism of transport of the passenger domain through the outer membrane.

RECENT PUBLICATIONS:

1-Dautin, N., Karimova, G., Ullmann, A. and Ladant, D. 2000. Sensitive genetic screen for protease activity based on a cyclic AMP signaling cascade in Escherichia coli. J. Bacteriol. 182: 7060-7066.

2-Dautin, N, Karimova, G and Ladant, D. 2002. Bordetella pertussis adenylate cyclase toxin: a versatile screening tool. Toxicon 40: 1383-1387.

3-Dautin, N, Karimova, G and Ladant, D. 2003. HIV-1 transframe protein can restore activity to a V82T dimerization-deficient HIV protease variant. J. Virol. 77: 8216-8226.

4-Vougier, S, Mary, J, Dautin, N, Vinh, J, Friguet, B and Ladant, D. 2004. Essential role of methionine residues in calmodulin binding to Bordetella pertussis adenylate cyclase, as probed by selective oxidation and repair by the peptide methionine sulfoxide reductases. J. Biol. Chem. 279: 30210-30218.

5-Karimova, G, Dautin, N and Ladant, D. 2005. Interaction network among Escherichia coli membrane proteins involved in cell division as revealed by bacterial two-hybrid analysis. J. Bacteriol. 187: 2233-2243

6-Dautin, N, Barnard, TJ, Anderson DE, Bernstein, HD. 2007. Cleavage of a bacterial autotransporter by an evolutionarily convergent autocatalytic mechanism. EMBO J. 26:1942-1952.

7-Dautin, N and Bernstein H.D. 2007. Proteins secretion in Gram-negative bacteria via the autotransporter pathway. Annu. Rev. Microbiol. 61:89-112.

8-Barnard, TJ, Dautin, N, Lukacik P, Bernstein HD and Buchanan SK. 2007 Autotransporter structure reveals intra-barrel cleavage followed by conformational changes. Nat. Struct. Mol. Biol. 14:1214-1220.