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TIGR leads Researchers in Sequencing Complete Genome of S. pneumoniae

NEW YORK, July 19 – A group of researchers led by The Institute for Genomic Research (TIGR) has sequenced the full genome of a virulent strain of Streptococcus pneumoniae , the bacterium that can cause pneumonia and meningitis, the researchers report in Friday’s issue of Science .

Last month, researchers with GlaxoSmithKline (GSK) in Europe published a paper in the journal Microbial Drug Resistance  containing a draft sequence of the organism’s genome that covered 90 percent of its total estimated size. The TIGR sequence contains hundreds of genes that are missing from the GSK draft version of the genome, said Claire Fraser, the lead author of the Science paper and TIGR director.

But the two papers found similarly important information from the organism’s genome about how the pathogen can evolve to escape the body’s immune system and resist the effects of antibiotic drugs. In the GSK study, researchers found over 47 whole or fragmented transposases, genetic elements that allow the bacterium to reshuffle the DNA within a chromosome, which could aid the organism’s efforts to evolve quickly. Similarly, Fraser and her team, led by principal investigator and TIGR researcher Hervé Tettelin, identified a large number of insertion sequences, representing about 5 percent of the total genome, that help “facilitate genomic recombination to generate diversity,” Fraser said.

Fraser’s team also found other clues to the pathogen’s resilience. S. pneumoniae  has the largest repertoire of transporters of any heterotrophic organism sequenced to date, she said, which means that it can incorporate many different types of chemicals without harm. In addition, the organism expresses a number of enzymes that promote adhesion and colonization of human cells, particularly in sugar-rich areas such as the respiratory tract.

The TIGR researchers, in collaboration with scientists at Johns Hopkins University, George Washington University, Bristol-Myers Squibb, the University of Illinois at Chicago, and the University of Alabama at Birmingham, sequenced the genome using the whole genome shotgun method, generating about 8x coverage of the sequence. The scientists used algorithms developed at TIGR to assemble the finished sequence from the fragments of sequenced DNA.

Fraser added that if all of TIGR’s sequencing resources had been devoted to the S. pneumoniae project, the sequencing effort would have taken just two days. Closing the gaps in the sequence, however, would have taken about three months, she added. In fact, partly because TIGR has 35 simulataneous sequencing projects, the entire effort took over five years.

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