Todd O. Kitten

Wood Building, Room 407   Dept. of Oral & Craniofacial Molecular Biol.   Virginia Commonwealth University   521 N. 11th St.   Richmond, VA 23298-0566	Tel: 804-628-7010 Fax: E-mail: tkitten@vcu.edu
Web: www.people.vcu.edu/~tkitten/
Research: Genome of Streptococcus sanguis and functional identification of virulence genes

BBSI project: What can the genomic sequence of Streptococcus sanguis tell us about how this bacterium causes disease?

A collaborative group here at VCU is determining the DNA sequence of the entire genome of the bacterium Streptococcus sanguis. This bacterium lives in the human mouth and attaches to teeth as part of dental plaque. By analysis of 16S ribosomal RNA, which is a traditional method for determining relatedness among organisms, S. sanguis is closely related to Streptococcus pneumoniae (which causes pneumonia) and more distantly related to Streptococcus mutans (which causes dental cavities). Yet, S. sanguis and S. mutans appear to be closely related ecologically, as they both attach to teeth as components of dental plaque and both cause infective endocarditis. The genomic sequences of S. pneumoniae and S. mutans have been determined. Based on the complete or near-complete sequence of S. sanguis, is this bacterium more closely related to S. mutans or S. pneumoniae? What is the best way to answer this question? If S. sanguis is more closely related to S. pneumoniae, why does it appear phenotypically to be more similar to S. mutans?

Other research interests (see web page for more details)

Research in the lab concerns virulence of oral streptococci in dental caries and in extra-oral diseases, especially endocarditis. The latter is characterized by infection of heart valves and subsequent impairment of function, and also frequently by serious complications such as heart attack and stroke. One focus of research is the characterization of an ABC-type metal uptake system in Streptococcus mutans. This system is required for S. mutans to cause endocarditis in an animal model and represents an attractive vaccine candidate. We are also working on identifying virulence factors required for Streptococcus sanguis to cause endocarditis. Our approach has been to adapt the technique of signature-tagged mutagenesis (STM) for use with S. sanguis. STM requires no prior assumptions concerning the importance of any particular gene or activity in disease causation. Instead, it relies on the infection process in an animal model to identify the bacterial genes needed for disease and their relative contributions. Our adaptation has involved the use of in vitro transposon mutagenesis for introducing tagged mutations into S. sanguis. We are currently in the process of creating, screening, and characterizing avirulent mutants of S. sanguis thus created. We are also involved in a project to sequence the genome of S. sanguis. Both the sequencing project and the STM project involve the same strain of S. sanguis. The two projects are complementary-the genome project provides sequence data for the STM project, while the STM project provides information concerning the function of genes identified by DNA sequencing.

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