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Published online on September 19, 2005, 10.1073/pnas.0506758102 OPEN ACCESS ARTICLE


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Genetics
Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: Implications for the microbial "pan-genome"

( bacterial species | comparative genomics | group B Streptococcus )

Hervé Tettelin a,b, Vega Masignani b,c, Michael J. Cieslewicz b,d,e, Claudio Donati c, Duccio Medini c, Naomi L. Ward a,f, Samuel V. Angiuoli a, Jonathan Crabtree a, Amanda L. Jones g, A. Scott Durkin a, Robert T. DeBoy a, Tanja M. Davidsen a, Marirosa Mora c, Maria Scarselli c, Immaculada Margarit y Ros c, Jeremy D. Peterson a, Christopher R. Hauser a, Jaideep P. Sundaram a, William C. Nelson a, Ramana Madupu a, Lauren M. Brinkac a, Robert J. Dodson a, Mary J. Rosovitz a, Steven A. Sullivan a, Sean C. Daugherty a, Daniel H. Haft a, Jeremy Selengut a, Michelle L. Gwinn a, Liwei Zhou a, Nikhat Zafar a, Hoda Khouri a, Diana Radune a, George Dimitrov a, Kisha Watkins a, Kevin J. B. O'Connor h, Shannon Smith i, Teresa R. Utterback i, Owen White a, Craig E. Rubens g, Guido Grandi c, Lawrence C. Madoff e,j, Dennis L. Kasper e,j, John L. Telford c, Michael R. Wessels d,e, Rino Rappuoli c,k,l, and Claire M. Fraser a,b,k,m

aInstitute for Genomic Research, 9712 Medical Center Drive, Rockville, MD 20850; cChiron Vaccines, Via Fiorentina 1, 53100 Siena, Italy; dDivision of Infectious Diseases, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115; eHarvard Medical School, Boston, MA 02115; fCenter of Marine Biotechnology, University of Maryland Biotechnology Institute, 701 East Pratt Street, Baltimore, MD 21202; gChildren's Hospital and Regional Medical Center, 307 Westlake Avenue N, Seattle, WA 98109; hThe Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218; iJ. Craig Venter Institute, 5 Research Place, Rockville, MD 20850; jChanning Laboratory, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115; and mGeorge Washington University Medical Center, 2300 Eye Street NW, Washington, DC 20037

Contributed by Rino Rappuoli, August 5, 2005

The development of efficient and inexpensive genome sequencing methods has revolutionized the study of human bacterial pathogens and improved vaccine design. Unfortunately, the sequence of a single genome does not reflect how genetic variability drives pathogenesis within a bacterial species and also limits genome-wide screens for vaccine candidates or for antimicrobial targets. We have generated the genomic sequence of six strains representing the five major disease-causing serotypes of Streptococcus agalactiae, the main cause of neonatal infection in humans. Analysis of these genomes and those available in databases showed that the S. agalactiae species can be described by a pan-genome consisting of a core genome shared by all isolates, accounting for {approx}80% of any single genome, plus a dispensable genome consisting of partially shared and strain-specific genes. Mathematical extrapolation of the data suggests that the gene reservoir available for inclusion in the S. agalactiae pan-genome is vast and that unique genes will continue to be identified even after sequencing hundreds of genomes.

Author contributions: R.R. designed research; H.T., V.M., M.J.C., C.D., D.M., N.L.W., S.V.A., J.C., A.L.J., A.S.D., R.T.D., T.M.D., M.M., M.S., I.M.y.R., J.D.P., C.R.H., J.P.S, W.C.N., R.M., L.M.B., R.J.D., M.J.R., S.A.S., S.C.D., D.H.H., J.S., M.L.G., L.Z., N.Z., H.K., D.R., G.D., K.W., K.J.B.O., S.S., T.R.U., C.E.R., and G.G. performed research; H.T., V.M., C.D., D.M., O.W., L.C.M., D.L.K., and M.R.W. analyzed data; and H.T., V.M., M.J.C., C.D., D.M., N.L.W., J.L.T., C.M.F., and R.R. wrote the paper.

Freely available online through the PNAS open access option.

bH.T., V.M., and M.J.C. contributed equally to this work.

kR.R. and C.M.F. contributed equally to this work.

lTo whom correspondence should be addressed.

Rino Rappuoli, E-mail: rino_rappuoli{at}chiron.com

www.pnas.org/cgi/doi/10.1073/pnas.0506758102
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