ROCKVILLE, MD -- Investigators at The Institute for Genomic Research (TIGR) today announced that they have determined the complete genome sequence of a virulent isolate (a very infectious strain) of Streptococcus pneumoniae or pneumococcus, the bacterium which causes over 3 million children and even more elderly people to die every year from pneumonia or meningitis. It is also the most common cause of otitis media or ear infection.
Hervé Tettelin, Ph.D., principal investigator for the project, led the team at TIGR that determined the order of all of the 2.16 million individual chemical base units making up S. pneumoniae's DNA. This study, reported in the July 20 issue of Science, represents the 26th genome sequencing project completed by TIGR.
S. pneumoniae is one of the most significant bacterial pathogens of humans in terms of morbidity and mortality and this situation is compounded by a progressive increase in antibiotic resistance, particularly to penicillin and to other commonly used antibiotics, that has been observed worldwide. This increased resistance complicates the ability to treat pneumococcal infections and is focusing greater attention on prevention strategies. Undoubtedly, the availability of the complete genome sequence will provide additional avenues for follow-up studies on the basic biology and pathogenicity of this important pathogen.
Genome analysis revealed a number of novel insights relevant to the biology of S. pneumoniae including: the observation that 5% of the genome is composed of repeats (pieces of DNA that are found in several locations in the genome) that may facilitate incorporation of foreign DNA into the S. pneumoniae chromosome and contribute to rearranging its structure; the description of a new sequence motif that may be involved in bringing proteins to the surface of the bacteria, including virulence factors and a novel large protein composed of 540 repeat modules that could play a role in adhesion to human cells; the possibility that S. pneumoniae occupies a microenvironment within the respiratory tract given its ability to transport and metabolize a wider range of sugars than other pathogens occupying the same niche; and the identification by means of microarrays of differences between strains that could explain their virulence behavior.
"While this project was a long time coming," said Claire M. Fraser, Ph.D., president and director of TIGR, "the availability of this information represents a tremendous milestone in helping to understand the virulence and pathogenicity of a highly infectious bacterium."
Tettelin adds that TIGR is now in the process of comparing this strain to a noninfectious strain and to other infectious strains including some that we already know are resistant to antibiotics. "By doing so," he says, "we will be able to identify the genes that determine the virulence of a specific strain as well as the virulence determinants common to all strains. The results of these analyses will be instrumental in the identification of new potential drug targets and vaccine candidates."
The sequence finishing phase of this project was funded in part by the National Institute of Allergy and Infectious Diseases (NIAID), a division of the National Institutes of Health (NIH); and by Merck Genome Research Institute (MGRI). This project was made possible by Grant Number 5UO1AI40645 from NIAID.
A detailed description of the S. pneumonia genome is available through TIGR's Comprehensive Microbial Resource (CMR) at (www.tigr.org/tigr-scripts/CMR2/CMRHomePage.spl).
The Institute for Genomic Research (TIGR) is a not-for-profit research institute founded in 1992 with interests in structural, functional and comparative analysis of genomes and gene products from a wide variety of organisms including viruses, eubacteria (both pathogens and non-pathogens), archaea (the so-called third domain of life), and eukaryotes (plants, animals, fungi and protists such as the malarial parasite). The first two complete genome sequences of free-living organisms (the bacteria Haemophilus influenzae and Mycoplasma genitalium) were determined at TIGR in 1995, as was the first complete genome sequence of an archaea (Methanococcus jannaschii) in 1996. TIGR also was the first to complete the sequence of a chromosome from the malarial parasite, Plasmodium falciparum, and from the model plant species, Arabidopsis thaliana. Additional information about TIGR is available at www.tigr.org.