Why do you think your paper is highly cited?

Streptococcus pneumoniae is a major human pathogen with a broad impact on world health. The S. pneumoniae research community is a large one, both because of the pathogen's wide impact on health and also because it was the organism used for the discovery that DNA is the carrier of genetic information.  As such, S. pneumoniae is a widely used molecular biology tool.

  Does it describe a new discovery or a new methodology that's useful to others?

For the first time investigators had access to the entire gene complement of this organism.  Also, the paper gave insights into species diversity using a new method called complete genome hybridization that uses DNA microarrays.

  What were some of the circumstances that led you to do this research?

It was a combination of factors—the importance of S. pneumoniae as a pathogen and its increasing antibiotic resistance, the demand for sequence information, and the availability of funding from NIH and Merck.

  Could you summarize the significance of your paper in layman's terms?

S. pneumoniae is one of the most significant bacterial pathogens of humans in terms of morbidity and mortality. 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 treatment of pneumococcal infections and is focusing greater attention on prevention strategies. 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 (insertions sequences) that may facilitate incorporation of foreign DNA into and contribute to rearrangements of the S. pneumoniae chromosome; 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.

This paper and Hervé Tettelin were also the Fast Breaking Paper in Microbiology for July 2002.

Hervé Tettelin
Associate Investigator 
The Institute for Genomic Research (TIGR)
Rockville, MD