Our laboratory has for some time been interested in the ability of pathogenic bacteria to obtain iron during growth in the human host; these studies are currently focusing on Neisseria meningitidis (the meningococcus), a common causative agent of the meningitis, particularly in infants and young children. N. meningitidis resides on the human upper respiratory mucosal surface, and can invade the bloodstream to cause septicemic disease. N. meningitidis obtains iron from human iron binding proteins by virtue of bacterial cell surface receptors for transferrin, lactoferrin and other iron carriers; the organism removes the iron from these proteins without producing a soluble iron chelator. Our current studies focus on the meningococcal HpuAB receptor, which we first described in 1995. This receptor allows the meningococcus to utilize hemoglobin and hemoglobin-haptoblobin complexes for growth, by removing the heme moiety from the protein. Our current studies focus on structure-function relationships in the HpuA and HpuB proteins, using site-directed mutagenesis and physiological measurements of ligand binding and internalization.

In 1995, we began to move into microbial genomics, and have completed the sequencing of the genomes of Neisseria gonorrhoeae (the causative agent of the human sexually transmitted disease gonorrhea) and Actinobacillus actinomycetemcomitans (a causative agent of human periodontal disease). We are currently sequencing the genomes of a nontypeable strain of Haemophilus influenzae (in collaboration with Drs. Lauren Bakaletz and Robert Munson at Ohio State University), Haemophilus somnus (a cattle pathogen, in collaboration with Dr. Tom Inzana at Virginia Tech), and Actinobacillus pleuropneumoniae (a swine pathogen). These data can be viewed on our web page for the Laboratory for Microbial Genomics (http://microgen.ouhsc.edu).

Associated with these studies, we have begun to develop bioinformatics tools useful for the biologist. We are fabricating DNA microarrays that will carry all of the known gonococcal ORFs, to be used to assess global gene expression profiles when the organism is grown under a variety of in vitro conditions thought to mimic in vivo growth. We are also using mass spectrometry methods to identify proteins that are expressed in these same conditions. Lastly, we have begun to move into molecular studies of microbial ecology, using 16S ribosomal RNA sequencing as a tool to examine the microbial ecosystem of the bovine rumen.



Figure legend: Linear comparison of the organization of the genomes of N. gonorrhoeae FA1090 (our data) and N. meningitidis strains MC58 (Tettelin, H., et al., Science 287: 1809-15, 2000) and Z2491 (Parkhill, J., et al., Nature 404: 502-6, 2000).

Selected Publications

1. Rohde, K.H., Gillaspy, A.F., Hatfield, M.D., Lewis, L.A., and D.W. Dyer. Interactions of hemoglobin with the Neisseria meningitidis receptor HpuAB: the role of TonB and an intact proton motive force. Mol. Microbiol. 43: 335-354, 2002.
2. Williams, B.A., A. Hendrickson, A.F. Gillaspy, D.W. Dyer and L.A. Lewis. Oligonucleotide Analysis by Sequential Injection Before Analysis (SIBA) Capillary Electrophoresis. Anal. Biochem. 313: 183-185, 2003.
3. Carson, M.B., J. Orvis, A.F. Gillaspy and D.W. Dyer. Sequal: A Graphical Representation of Phrap Quality Scores for Consensus Sequences. (submitted to Bioinformatics).
4. Orvis, J., M. Carson, A.F. Gillaspy and D.W. Dyer. blaSTOR: An Access database for automating BLAST storage and analysis. (submitted to Bioinformatics).
5. Ralph, D., D. Tamalis, D. Dyer, K. Hartman, W. Phillips, S. Coleman, C. Aston and J. Iandolo. Assessing bacterial diversity in the bovine rumen microflora in response to diet using 16S rDNA sequencing. (submitted to Applied and Environmental Microbiology).
6. Lewis, L.A., A. Gillaspy, R. McLaughlin, M. Gipson, T. Ducey, T. Ownbey, K. Hartman, C. Nydick, M. Carson, J. Vaughn, C. Thomson, L. Song, S. Lin, X. Yuan, F. Najar, M. Zhan, Q. Ren, H. Zhu, S. Qi, S. Kenton, H. Lai, J. White, S. Clifton, B.A. Roe and D.W. Dyer. The complete genome sequence of Neisseria gonorrhoeae (in preparation).

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Last edited 11/09/07 Please send comments, questions, or error reports to cheryl-murphy@ouhsc.edu Copyright © 2007 The Board of Regents of the University of Oklahoma, All Rights Reserved University of Oklahoma Disclaimers