Borreliose-Gesellschaft e.V.

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How do Lyme Borrelia cause disease? The quest for virulence determinants
Steven J. Norris, Ph.D.

Professor and Vice Chair for Research
Depts. of Pathology & Laboratory Medicine and Microbiology & Molecular Genetics
UTHealth Medical School, Houston, Texas, U.S.A.

Lyme disease Borrelia are among a small group of bacteria that are invasive, persistent pathogens.  They express no known toxins, and very few virulence determinants (bacterial products required for infection and pathogenesis) have been identified.  To identify additional vur laboratory has developed a defined library of 4,480 B. burgdorferi mutants using random insertion of a modified version of the mariner transposon Himar1.  Eleven different 7 base pair ‘signature tags’ were added to the transposon to permit the infection of mice with combinations of different mutants and assessment of each mutant’s infectivity using a Luminex®-based, high-throughput PCR procedure. The insertion site of each mutant (and thus the gene inactivated) was identified precisely by sequencing. The plasmid content of each clone was also ascertained by a Luminex® approach.  In preliminary analyses, we have determined the infectivity of over 200 mutants, including those in which lipoprotein genes and genes involved in nutrient transport, motility and chemotaxis had been inactivated.  The transposon mutant library has been utilized to assess the effects of mutations on the flagellar motor of B. burgdorferi, as determined by cryo-electron microscopy.  In addition, mutations in genes important in DNA recombination and repair were examined for their effects on VlsE antigenic variation, a vital role in Lyme Borrelia immune evasion. 

In summary, the signature tagged mutagenesis (STM) approach shows great promise in identifying borrelial factors important in pathogenesis, which should in turn improve our understanding of how Lyme Borrelia cause disease.

Dr. Norris is currently the Robert Greer Professor in Biomedical Sciences and vice chair of pathology and laboratory medicine at the University of Texas Medical School at Houston. Dr. Norris began his faculty career at the University of Texas Medical School at Houston in 1982 and continued studies on the physiology and in vitro culture of Treponema pallidum, the spirochete that causes syphilis. His group is currently screening a transposon insertion library in B. burgdorferi in an attempt to identify every gene important in Lyme disease pathogenesis. He is a Fellow of the American Academy of Microbiology, and has served as the chair of the American Society for Microbiology Division of General Medical Microbiology and of the Gordon Research Conference on the Biology of Spirochetes.  Dr. Norris received a B.A. in psychobiology at the University of California, Los Angeles (UCLA), then gradually evolved toward microbiology while obtaining an M.S. in biochemistry and molecular biology at UC Santa Barbara, and a Ph.D. in microbiology and immunology at UCLA in 1980.