Assistant Professor

Ph.D., 2001 University of North Dakota School of Medicine
Postdoctoral Fellow 2001-2002 IUPUI, Indianapolis
Postdoctoral Fellow 2002-2006 Rocky Mountain Labs, NIH/NIAID

Program Affiliation: Molecular Biology & Genetics | Microbiology

Research Groups Affiliation: Biochemistry | Cell Biology | Genetics | Microbiology

Phone: 812/856-2813
Fax: 812/855-6705
Email David

Chlamydiae are obligatory intracellular parasites that exhibit a unique bi-phasic developmental cycle inside eukaryotic cells.  Chlamydiae are ubiquitous pathogens of mammals and cause a number of serious human diseases, including blinding trachoma (the leading cause of preventable blindness), sexually transmitted infections (estimated at 4 million new cases in the US alone in 2005), and pneumonia, and may contribute to chronic diseases such as arthritis and atherosclerosis.  There is no vaccine against any human chlamydial disease.  Unfortunately, a lack of genetic tools has complicated study of chlamydial pathogenesis. 

The short term goal of our research is to identify and characterize strain- and species-specific pathogenicity factors that determine the host ranges and tissue tropisms of chlamydiae.  Long term, we hope to apply these findings towards rational vaccine design and improved animal models of human chlamydial infection. 

Specific projects include: 

1. Characterization of pathogenicity factors in the plasticity zone

The genomes of C. trachomatis strains that cause distinct diseases including mucosal sexually transmitted infections (serovars D-K), lymphogranuloma venereum (serovars L1-L3) and trachoma (serovars A-C) share greater than 99% sequence identity.  Genetic variation among these strains predominately maps to a short region of the genome termed the plasticity zone (PZ).  Two strain-variable PZ gene families, the chlamydial cytotoxins and phospholipase D homologs, share homology with well-characterized virulence factors of other pathogens.  We are currently attempting to identify the targets of these pathogenicity factors in collaboration with Dr. Harlan Caldwell (Rocky Mountain Labs, NIH/NIAID) using a variety of genetic, biochemical and in vivo approaches.   

2. Isolation and characterization of attenuated chlamydiae

Most C. trachomatis genes are highly conserved, suggesting these “core component” genes perform critical functions, possibly making them difficult targets for knockout.  In contrast, variability in pathogenicity factors in the PZ among C. trachomatis strains that develop normally in vitro, suggests PZ genes may be amenable to manipulation.  We are currently assessing the feasibility of various techniques to generate large pools of randomly mutagenized chlamydiae.  We hypothesize mutations in surviving strains will locate primarily in PZ genes because core component mutants will be lost to purifying selection.  Specific PZ mutants will be isolated using an assortment of phenotypic screens and selections in vitro, and re-sequenced.  Next, we propose to determine if PZ mutants are attenuated in vivo and to characterize the immune responses they elicit in mouse models of human chlamydial infection. 

3. Development of forward genetic approaches for analysis of chlamydial-host interactions

We are currently developing forward genetic approaches to identify host proteins necessary for chlamydial development in vitro.  First, we are screening the human genome to identify genes that impart resistance to chlamydial infection using global siRNA libraries delivered by recombinant viral vectors.  In a complementary approach Chlamydia-resistant host cells are being selected from pools of pseudodiploid host cells insertionally mutagenized with transposons.  Both approaches may yield exciting insights into the molecular mechanisms of chlamydial-host interactions.

Kari L, Whitmire WM, Carlson JH, Crane DD, Reveneau N, Nelson DE, Mabey DC, Bailey RL, Holland MJ, McClarty G and HD Caldwell. 2008. Pathogenic diversity among Chlamydia trachomatis ocular strains in non human primates is affected by subtle genomic variations.  Journal of Infectious Disease, EPUB, Jan 16th.

Nelson DE, Taylor LD, Shannon, JG, Whitmire WM, Crane DD, McClarty G, Su H, Kari L and HD Caldwell. 2007. Phenotypic rescue of Chlamydia trachomatis growth in IFN-g treated mouse cells by irradiated Chlamydia muridarum.  Cellular Microbiology. 9(9):2289-98.

McClarty G, Caldwell HD and DE Nelson. 2007. Chlamydial interferon gamma immune evasion influences infection tropism. Current Opinion in Microbiology. 10:1-5.

Nelson DE, Crane DD, Taylor LD, Dorward DW, Goheen MM and HD Caldwell. 2006.  Inhibition of Chlamydiae by primary alcohols correlates with the strain-specific complement of plasticity zone phospholipase D genes. Infection Immunity. 74(1):73-80.

Nelson DE, Virok DP, Wood H, Roshick C, Johnson RM, Whitmire WM, Crane DD, Steele-Mortimer O, Kari L, McClarty G and HD Caldwell.  2005 Chlamydial interferon gamma immune evasion is linked to host infection tropism.  PNAS. 102(30):10658-63.

Virok DP, Nelson DE, Whitmire WM, Crane DD, Goheen MM and HD Caldwell. 2005.  Chlamydial infection induces pathobiotype-specific protein tyrosine phosphorylation in epithelial cells. Infection Immunity. 73(4):1939-46.

Belland, RJ, Nelson DE, Crane DD, Hogan D, Sturdevant D, Beatty WL and HD Caldwell. 2003.  Transcriptome analysis of chlamydial growth during IFN-g mediated persistence and reactivation. PNAS. 100(26):15971-6.

Nelson DE, Ghosh A, Paulson A and KD Young.  2002. Contribution of membrane-binding and enzymatic domains of penicillin binding protein 5 to maintenance of uniform cellular morphology of Escherichia coli. Journal of Bacteriology. 184:3630-9. 

Nelson DE and KD Young.  2001.  Contributions of PBP 5 and DD-carboxypeptidase penicillin binding proteins to maintenance of cell shape in Escherichia coli.  Journal of Bacteriology. 183:3055-64.

Nelson DE and KD Young.  Penicillin binding protein 5 affects cell diameter, contour, and morphology of Escherichia coli. 2000. Journal of Bacteriology. 182(6):1714-21.