5018-Nelson, David
Faculty

David E. Nelson, PhD

Associate Professor of Microbiology & Immunology

Bio

Dr. Nelson completed his Ph.D. in the laboratory of Dr. Kevin Young at the University of North Dakota School of Medicine where he studied the functions of peptidogylcan remodeling enzymes in Escherichia coli. He subsequently completed a postdoctoral fellowship in Dr. Harlan Caldwell's laboratory at the National Institutes of Allergy and Infectious Diseases, Rocky Mountain laboratories, where he trained in chlamydial pathogenesis.

Dr. Nelson's group currently works in two distinct, but sometimes, overlapping areas of microbial pathogenesis. One focus is the identification and characterization of chlamydial virulence factors that allow these pathogens to target specific tissues and circumvent immunity. His group has already identified several factors that mediate chlamydial tissues tropism and immune evasion. Long-term goals of these projects are the identification of suitable vaccine antigens and the design of efficacious anti-chlamydial vaccines. A second focus of his laboratory is urogenital pathogen discovery. These projects apply powerful "omics" type approaches (microbiome, proteome, genome, transcriptome) to specimens from large clinical cohorts. Dr. Nelson's group was the first to demonstrate that the distal urethras of men support microbial communities that resemble those present in the vagina, and contributed to the discovery of a novel clade of Neisseria meningitidis which is an emerging uropathogen. Long-term goals of these projects are  the discovery of novel and emerging urogenital pathogens, the development of improved treatment modalities for urogenital infections, and the design of diagnostics for improved evaluation of urogenital disease.

Key Publications

Neisseria meningitidis ST11 Complex Isolates Associated with Nongonococcal Urethritis, Indiana, USA, 2015-2016. Toh E, Gangaiah D, Batteiger BE, Williams JA, Arno JN, Tai A, Batteiger TA, Nelson DE. Emerg Infect Dis. 2017. 23(2):336-339.

 

Generation of targeted Chlamydia trachomatis null mutants. Kari L, Goheen MM, Randall LB, Taylor LD, Carlson JH, Whitmire WM, Virok D, Rajaram K, Endresz V, McClarty G, Nelson DE, Caldwell HD. Proc Natl Acad Sci U S A. 2011. 108(17):7189-93.

 

Beyond Tryptophan Synthase: Identification of Genes That Contribute to Chlamydia trachomatis Survival during Gamma Interferon-Induced Persistence and Reactivation. Muramatsu MK, Brothwell JA, Stein BD, Putman TE, Rockey DD, Nelson DE. Infect Immun. 2016. 84(10):2791-801.

 

Interrogating Genes That Mediate Chlamydia trachomatis Survival in Cell Culture Using Conditional Mutants and Recombination. Brothwell JA, Muramatsu MK, Toh E, Rockey DD, Putman TE, Barta ML, Hefty PS, Suchland RJ, Nelson DE. J Bacteriol. 2016. 198(15):2131-9.

Characteristic male urine microbiomes associate with asymptomatic sexually transmitted infection. Nelson DE, Van Der Pol B, Dong Q, Revanna KV, Fan B, Easwaran S, Sodergren E, Weinstock GM, Diao L, Fortenberry JD. PLoS One. 2010. 5(11):e14116.

Titles & Appointments

  • Associate Professor of Microbiology & Immunology
  • Associate Professor of Medicine
  • Education
    2001 PhD University of North Dakota
  • Research

    Chlamydial pathogenesis, microbiome pathogen interactions and pathogen discovery

    Chlamydiae are obligate intracellular parasites that live inside eukaryotic cells. The human chlamydial disease burden is massive and increasing, and pathogens in the genus Chlamydia are the most common infectious agents of blindness and bacterial sexually transmitted infections. Reasons these infections are so common include that no anti-chlamydial vaccines have been developed and infection does not usually elicit lasting immunity. How these pathogens cause disease and evade immunity is poorly understood because chlamydiae were intractable to genetic manipulation until recently. However, the last few years have seen many firsts in chlamydial genetics including transformation, allelic exchange and mutagenesis; the pathogenesis of these organisms can now be investigated using classical bacterial genetic strategies. My lab is using these new tools, and developing improved tools to understand the molecular basis of how highly similar Chlamydia species infect different hosts and how the same Chlamydia isolates infect different tissues (eye, urogenital tract, GI tract, lungs). More recently, we began studying interactions of C. trachomatis with the urogenital and gastrointestinal microbiomes. This work revealed an unexpectedly diverse male urogenital tract microbiota. We are now investigating if the composition of genital and gastrointestinal microbiomes is pertinent to C. trachomatis susceptibility and transmission in humans, and if some of the novel microorganisms we have recently identified are pathogens themselves, using a combination of metagenomic, immunological and epidemiological approaches.

    Specific projects currently active in my laboratory include:

    1. Identification of C. muridarum genes that dictate host tropism: We model human chlamydial in disease in mice using the mouse-adapted strain C. muridarum because the C. trachomatis strains that infect humans are quickly cleared in mice. A long-standing goal of the lab is to identify C. muridarum pathogenic determinants that that this pathogen uses to survive in mice and the cognate host immune defenses mechanisms these determinants counter. The longer goal of this work is develop better mouse models of human chlamydial infection and disease which we can use to evaluate new anti-chlamydial vaccines and therapeutics.

    2. Identification of determinants of chlamydial pathogenesis. Most chlamydial genes are highly conserved, even in pathogenically distinct species. Core genes mediate shared aspects of chlamydial intracellular biology whereas species and strain specific-virulence factors may mediate niche specialization. We are using mutagenesis, forward genetic screens, and various reverse genetic approaches  to identify virulence factors that mediate chlamydial resistance to pro-apoptotic stimuli, cell-autonomous immunity and which help these pathogens invade different tissues. Separately, we are developing tools for manipulation of essential chlamydia genes that dictate broadly conserved aspects of chlamydial pathogenesis and intracellular biology.

    3. Microbiome of the human urogenital tract and pathogen discovery: The male urogenital tract has classically been thought to be sterile. Results from our and other groups challenge this idea and suggest that uncharacterized microorganisms that colonize the urogenital and GI tracts and may be relevant to diseases of known (such as Chlamydia) and unknown etiologies. We are currently investigating the hypotheses that specific urethral microbiomes promote susceptibility to chlamydial infection and disease and that idiopathic urethritis is caused by novel urogenital microorganisms by comparing the microbiomes hundreds of men who do and do not have urethritis before and after antibiotic treatment. Separately, we are interested in how microbiomes of various body sites influence susceptibility to pathogens.

  • Publications
    Cutaneous Burn Injury Promotes Shifts in the Bacterial Microbiome in Autologous Donor Skin: Implications for Skin Grafting Outcomes.
    Plichta JK; Gao X; Lin H; Dong Q; Toh E; Nelson DE; Gamelli RL; Grice EA; Radek KA; Shock (Augusta, Ga.) 2017 Oct
    Advances and Obstacles in the Genetic Dissection of Chlamydial Virulence.
    Brothwell JA; Muramatsu MK; Zhong G; Nelson DE; Current topics in microbiology and immunology 2017 Nov 1
    Quantity of alcohol drinking positively correlates with serum levels of endotoxin and markers of monocyte activation.
    Liangpunsakul S; Toh E; Ross RA; Heathers LE; Chandler K; Oshodi A; McGee B; Modlik E; Linton T; Mangiacarne D; Jimenez C; Dong XC; Wang L; Tu W; Nelson DE; Scientific reports 2017 Jun 30
    Cutaneous Burn Injury Modulates Urinary Antimicrobial Peptide Responses and the Urinary Microbiome.
    Plichta JK; Holmes CJ; Nienhouse V; Puszynski M; Gao X; Dong Q; Lin H; Sinacore J; Zilliox M; Toh E; Nelson DE; Gamelli RL; Radek KA; Critical care medicine 2017 Jun
    The Genital Tract Virulence Factor pGP3 Is Essential for Chlamydia muridarum Colonization in the Gastrointestinal Tract.
    Shao L; Zhang T; Melero J; Huang Y; Liu Y; Liu Q; He C; Nelson DE; Zhong G; Infection and immunity 2017 Dec 19
    Emergence of a new <i>Neisseria meningitidis</i> clonal complex 11 lineage 11.2 clade as an effective urogenital pathogen.
    Tzeng YL; Bazan JA; Turner AN; Wang X; Retchless AC; Read TD; Toh E; Nelson DE; Del Rio C; Stephens DS; Proceedings of the National Academy of Sciences of the United States of America 2017 Apr 3
    Sequestration of host metabolism by an intracellular pathogen.
    Gehre L; Gorgette O; Perrinet S; Prevost MC; Ducatez M; Giebel AM; Nelson DE; Ball SG; Subtil A; eLife 2016 Mar 16
    Effect of Advanced HIV Infection on the Respiratory Microbiome.
    Twigg HL 3rd; Knox KS; Zhou J; Crothers KA; Nelson DE; Toh E; Day RB; Lin H; Gao X; Dong Q; Mi D; Katz BP; Sodergren E; Weinstock GM; American journal of respiratory and critical care medicine 2016 Jul 15
    Interrogating Genes That Mediate Chlamydia trachomatis Survival in Cell Culture Using Conditional Mutants and Recombination.
    Brothwell JA; Muramatsu MK; Toh E; Rockey DD; Putman TE; Barta ML; Hefty PS; Suchland RJ; Nelson DE; Journal of bacteriology 2016 Jul 13
    Chlamydia trachomatis Is Resistant to Inclusion Ubiquitination and Associated Host Defense in Gamma Interferon-Primed Human Epithelial Cells.
    Haldar AK; Piro AS; Finethy R; Espenschied ST; Brown HE; Giebel AM; Frickel EM; Nelson DE; Coers J; mBio 2016 Dec 13
    Household air pollution and the lung microbiome of healthy adults in Malawi: a cross-sectional study.
    Rylance J; Kankwatira A; Nelson DE; Toh E; Day RB; Lin H; Gao X; Dong Q; Sodergren E; Weinstock GM; Heyderman RS; Twigg HL 3rd; Gordon SB; BMC microbiology 2016 Aug 11
  • Professional Organizations
    American Society for Microbiology
  • Clinical Interests

    I currently direct a large case/control clinical study which is assessing if novel pathogens are linked to a common but undefined urogenital syndrome, idiopathic urethritis, in men. More broadly, I am interested in improving the standard of care for urogenital tract infections. Finally, I study factors that could modulate susceptibility to Chlamydia infection, detrimental outcomes of these infections, and the mechanisms of immune protection against Chlamydia and other urogenital tract pathogens.

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