Lab Research Focus
My laboratory does pathogenetic studies on the bacterium Streptococcus pneumoniae. Infections with this agent kill several million children and adults world wide, especially in developing countries. These infections are also especially deleterious in immunosuppressed or asplenic individual, for those with AIDS, or in individuals with sickle cell disease. Projects ongoing in the laboratory are diverse, and many revolve specifically around issues of microbial diversity in bacterial pathogenesis.
In a longstanding collaboration with D. Hervé Tettelin at Institute for Genomic Sciences (IGS) at University of Maryland and with funding from the National Institutes of Health, we are examining the broad question of diversity within all strains within the species Streptococcus pneumoniae. We have used comparative genome hybridization and genomic sequencing to explore a large number of strains within the bacterial strains that have serogroup 6 capsules. Not only is the genome diverse, but there is extensive and dynamic genome plasticity. We sequenced the first complete genome and several others, including a key highly penicillin-resistant pneumococcal clone and others selected to encompass diversity of the species. Some of our data is available at http://genome.microbio.uab.edu/strep/ and a comparative site for the 33 genomes is at http://strepneumo-sybil.igs.umaryland.edu/cgi-bin/current/shared/index.cgi?site=strepneumo. The genome plasticity has strong implication for the employment of vaccines and other disease interventions.
Our diversity studies also extend to diversity as it applies in the development of a third generation vaccine for the pneumococcus. Many of the candidate antigens for protein-based vaccines are beginning to progress through clinical trials. For all of them, there are unanswered questions as to the requirements for longterm immunological memory and immunity. Also, little is known about the impact that antigen diversity or genome diversity might have on vaccine efficacy. Hence, our studies target the mode of action and the potential for immunity for candidate proteins, specifically PcpA, NanA, PspA, PspC and pneumolysin. By understanding the pathogenetic role of each protein we hope to better understand its potential for generating immune protection.
To assist in the global effort to find a means of reducing the burden of pneumococcal disease in developing world sites, we are part (along with the Centers for Disease Control and Emory University) of a project funded by Path Vaccines in which a Global Strain Bank is being set up that will contain well-characterized bacterial isolates from sites that have a high burden of pneumococcal disease. The diversity of alleles for different vaccine candidates are being screened for these strains so that the potential of new vaccines to cover the higher diversity of strains found in these sites can be understood and planned for.
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