Shelley E. Haydel
My research program encompasses two distinct projects that have a common clinical link addressing how mycobacterial pathogens cause disease in humans.
The first project involves performing basic molecular biology research aimed at understanding the genetic intricacies of Mycobacterium tuberculosis which allow this organism to be an extraordinarily successful human pathogen. The World Health Organization declared tuberculosis to be a global health emergency in 1993. With 1/3 of the world´s population infected, ~7 million new cases of tuberculosis disease per year, and 2 million deaths per year, tuberculosis continues to be a global health challenge. My lab uses microbiology, molecular biology, genetics, biochemistry, and cell biology to investigate how two-component system regulatory proteins are responsible for various M. tuberculosis disease processes in humans. We aim to determine when these regulatory systems are important for host-pathogen interactions, how they impose regulatory control that influences M. tuberculosis pathogenesis, and how the molecular mechanisms of control are unique in M. tuberculosis. Since two-component regulatory proteins can be essential for bacterial viability and growth, are conserved across nearly all bacteria, and can be important for bacterial pathogenesis, they are ideal proteins for which to target for drug discovery. The long-term goal is to translate our understanding of these mechanisms into novel targets for antibiotic discovery or into existing or improved vaccines and vaccine strategies.
The second research project in my lab builds on clinical observations showing that specific natural minerals are effective at healing patients with Buruli ulcer, a necrotic skin infection caused by Mycobacterium ulcerans. Infection with M. ulcerans leads to extensive destruction of skin and soft tissue, often with the formation of very large ulcers. Since 1980, Buruli ulcer has emerged rapidly in several parts of the world, particularly West Africa, yet the disease has received considerably less global attention than other infectious diseases. In response to this, in 2004, the WHO declared Buruli ulcer to be a global health threat. Several years ago, a humanitarian began treating Buruli ulcer patients in western Africa with two different French minerals and documented 50 cases of the ability to heal these ulcerative skin lesions with hydrated minerals. My laboratory is investigating the antibacterial properties of specific natural minerals, the physicochemical properties of these antibacterial minerals, and the mechanisms by which these minerals promote bactericidal and/or bacteriostatic activity. If we can understand the mechanism by which these natural minerals are inhibiting the growth of bacterial pathogens and allowing patients infected with Buruli ulcer to heal, then we potentially have a identified a substance that acts as a therapeutic agent, that is naturally available resource, that can be applied topically, and that has few special handling requirements.
Selected Publications
Williams, L. B. and S. E. Haydel. 2008. Evaluation of the medicinal use of clay minerals as antibacterial agents. International Geology Review. In press.
Williams, L. B., S. E. Haydel, R. F. Giese, Jr., D. D. Eberl. 2008. Chemical and mineralogical characteristics of French green clays used for healing. Clays and Clay Minerals. 56:437-452.
Haydel, S. E., C. M. Remenih, L. B. Williams. 2008. Broad-spectrum in vitro antibacterial activities of clay minerals against antibiotic-susceptible and antibiotic-resistant bacterial pathogens. J. Antimicrob. Chemother. 61:353-361.
Haydel, S. E. and J. E. Clark-Curtiss. 2006. The Mycobacterium tuberculosis TrcR response regulator represses transcription of the intracellularly-expressed Rv1057 gene, encoding a seven-bladed β-propeller. J. Bacteriol. 188:150-159.
Haydel, S. E. and J. E. Clark-Curtiss. 2004. Global expression analysis of two-component system regulators during Mycobacterium tuberculosis growth in human macrophages. FEMS Microbiol. Lett. 236:341-347.
Clark-Curtiss, J. E. and S. E. Haydel. 2003. Molecular genetics of Mycobacterium tuberculosis pathogenesis. Ann. Rev. Microbiol. 57:517-549.
Haydel, S. E., W. H. Benjamin, Jr., N. E. Dunlap, J. E. Clark-Curtiss. 2002. Expression, autoregulation, and DNA binding properties of the Mycobacterium tuberculosis TrcR response regulator. J. Bacteriol. 184:2192-2203.
Haydel, S. E., N. E. Dunlap, W. H. Benjamin, Jr. 1999. In vitro evidence of two-component system phosphorylation between the Mycobacterium tuberculosis TrcR/TrcS proteins. Microb. Pathog. 26:195-206.