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Tao Lin, DVM

Associate Professor
Pathology & Laboratory Medicine
(713) 500 - 5350
Tao.Lin@uth.tmc.edu

Research Interests

• Bacteria genetics
• Bacteria pathogenesis
• Functional genomics
• Metagenomics
• Emerging tick-transmitted disease
• Pathogenomics

We use the spirochete Borrelia burgdorferi as a model bacterium to study the fundamental aspects of bacteria pathogenesis and its relationship with microbial physiology, structure, and genetics. We are also exploring the etiology of an emerging tick-borne disease, Southern Tick-Associated Rash Illness. Lyme disease is the most common tick-borne disease. The causative agent is Borrelia burgdorferi. This highly invasive spirochete is an obligate parasite in both ticks and mammals and produces no known toxins, but is able to colonize, disseminate, and invade almost any tissue from humans and animals, establish persistent infection for months to years in the presence of an active immune response, induce inflammatory responses and tissue damage, and thus serve as a models for the study of persistent infection of invasive bacteria. Little is known about the mechanisms of pathogenesis in B. burgdorferi. We ask the question what genes in the B. burgdorferi genome are responsible for the pathogenesis and long-term survival, and how can these genes be identified? Our strategy is to analyze the B. burgdorferi virulence determinants by Signature-Tagged Mutagenesis in combination with Luminex®-based high-throughput screening procedures, and infectivity studies to identify genes and gene products required for infectivity in a mouse model.
The identification of genes important in the pathogenesis of Lyme disease Borrelia has been hampered by the lack of well-developed genetic systems and exceedingly low transformation rates in low passage, infectious organisms. Signature-tagged mutagenesis is a powerful negative selection method that has been widely used to identify bacterial virulent factors required for the successful adhesion, colonization, and dissemination in the host. We developed a signature-tagged mutagenesis system for the isolation of borrelial virulence genes and gene products required for infectivity in a mouse model. A Luminex® FlexMapTM technology has been developed as a high-throughput method and has been used to identify and screen the virulent determinants important in the pathogenesis of Lyme disease. Thus far, we have created and constructed a high density, sequence defined transposon library of over 6,600 STM mutants for the efficient genome-wide investigation of genes and gene products required for wild-type pathogenesis, in vitro growth and in vivo survival, physiology, morphology, structure, and plasmid replication. The insertion sites of 4,480 transposon mutants have been determined. More than 800 genes in chromosome and plasmids have been inactivated, the infectivity of these mutants and function of these genes are being determined and characterized. We are currently applying 'functional genomics and pathogenomics' to elucidate the function, metabolism, structure, and pathogenic mechanisms of Borrelia based on their functional categories. For instance, we characterized the mutations in 23 genes involved in DNA recombination and repair, the results indicated that transposon mutants in ruvA, ruvB, and mutS exhibited reduced infectivity in mice and greatly diminished vlsE recombination. RuvA, RuvB, and MutS are the first trans-acting factors identified as necessary for vlsE recombination and antigenic variation. The result of this study will be a comprehensive view of the B. burgdorferi genes required for mammal-tick infectious cycle, and will fuel the detailed analysis of the functional roles of these genes in future years.
Illnesses consistent with Lyme disease have been reported in Texas and the south central U.S. Because the causative agent has not been isolated from patients, the term "Southern Tick-Associated Rash Illness" (STARI) was recently introduced by the CDC to describe this syndrome. To date no one has been able to identify, characterize, or culture organisms associated with STARI. We apply different approaches to the identification of organisms associated with STARI. We believe that this approach will significantly advance our understanding of STARI, and, more generally, the biology of tick-transmitted diseases and provide avenues for the systematic diagnosis, treatment, and prevention of this disease.