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Herve Tettelin, PhD

Academic Title:

Associate Professor

Primary Appointment:

Microbiology and Immunology

Additional Title:

Associate Professor, Institute for Genome Sciences

Location:

Biopark II office 629, 801 W. Baltimore Street

Phone (Primary):

(410) 706-6764

Fax:

(410) 706-1482

Education and Training

I received the degree of Industrial Engineer in Biotechnology from the Institut Supérieur Industriel de la Province de Liège, Belgium, and my B.S. and Ph.D. in Applied Natural Sciences from the Université Catholique de Louvain, Belgium. I was a postdoctoral fellow and a faculty member at the Institute for Genomic Research (TIGR) / J. Craig Venter Institute (JCVI) in Rockville, MD from 1997 to 2007. I am currently a tenured Associate Professor at the  Institute for Genome Sciences (IGS).

Biosketch

I have been in the genomics field for 25 years and I have developed an extensive expertise in microbial genomics, functional genomics, comparative genomics, and bioinformatics. I have led the genome sequencing and analysis of many organisms, starting with eukaryotic chromosomes then shifting towards bacterial pathogens. I was the lead author on the first published genomes of  Neisseria meningitidis,  Streptococcus pneumoniae, and  Streptococcus agalactiae. In collaboration with the group of Dr. Rino Rappuoli (GlaxoSmithKline, former Chiron Vaccines and Novartis Vaccines and Diagnostics), I pioneered the fields of reverse vaccinology and pan-genomics. The former makes use of genomics to identify novel protein candidates for vaccine development. The latter is the characterization of the genome content of an entire species using multiple strains. I have conducted many studies of bacterial diversity and transcriptional profiling using DNA microarrays and RNA-seq, as well as functional genomics analyses to identify genes essential for virulence in streptococci using Tn-seq. I have also supervised the development of bioinformatics tools to compare closely related bacterial genomes.

Research/Clinical Keywords

Bacterial pathogens, comparative genomics, functional genomics, RNA-seq, Tn-seq, bioinformatics.

Highlighted Publications

Blanchette K.A., Shenoy A.T., Milner II J., Gilley R.P., McClure E., Hinojosa C.A., Kumar N., Daugherty S.C., Tallon L.J., Ott S., King S.J., Ferreira D.M., Gordon S.B., Tettelin H., and Orihuela C.J (2016Neuraminidase-exposed galactose promotes Streptococcus pneumoniae biofilm formation during colonization. Infect. Immun. 84, 2922-2932. doi: 10.1128/IAI.00277-16.

Hooven T.A., Catomeris A.J., Akabas L.H., Randis T.M., Maskell D.J., Peters S.E., Ott S., Santana-Cruz I., Tallon L.J., Tettelin H., and Ratner A.J. (2016) The essential genome of Streptococcus agalactiae. BMC Genomics 17, 406. doi: 10.1186/s12864-016-2741-z.

Chancey S.T., Agrawal S., Schroeder M.R., Farley M.M., Tettelin H.*, and Stephens D.S.* [*These authors have contributed equally to this work] (2015) Composite mobile genetic elements disseminating macrolide resistance in Streptococcus pneumoniae. Front. Microbiol. 6, 26. doi: 10.3389/fmicb.2015.00026.

Vernikos G., Medini D., Riley D.R., and Tettelin H. (2015) Ten years of pan-genome analysesCurr. Opin. Microbiol. 23, 148-154.

Bessen D.E., McShan W.M., Nguyen S.V., Shetty A., Agrawal S., and Tettelin H. (2014) Molecular epidemiology and genomics of group A Streptococcus. Infect. Genet. Evol. (MEEGID). pii: S1567-1348(14)00382-7. doi: 10.1016/j.meegid.2014.10.011.

Kilian M., Riley D.R., Jensen A., Brüggemann H., and Tettelin H. (2014) Parallel evolution of Streptococcus pneumoniae andStreptococcus mitis to pathogenic and mutualistic lifestylesmBio 5, e01490-14. doi:10.1128/mBio.01490-14.

Additional Publication Citations

Other highlighted publications (see my complete list of publications in reverse chronological order below)

 

Chancey S.T., Bai X., Kumar N., Drabek E.F., Daugherty S.C., Colon T., Ott S., Sengamalay N., Sadzewicz L., Tallon L.J., Fraser C.M.,Tettelin H. and Stephens D.S. (2015Transcriptional attenuation controls macrolide inducible efflux and resistance in Streptococcus pneumoniae and in other Gram-positive bacteria containing mef/mel(msr(D)) elementsPLoS One 10, e0116254. doi: 10.1371/journal.pone.0116254.

Tettelin H., Davidson R.M., Agrawal S., Aitken M., Shallom S., Hasan N.A., Strong M., Calado Nogueira de Moura V., De Groote M.A., Duarte R.S., Hine E., Parankush S., Su Q., Daugherty S.C., Fraser C.M., Brown-Elliott B.A., Wallace Jr. R.J., Holland S.M., Sampaio E.P., Olivier K.N., Jackson M., and Zelazny A.M. (2014) High-level relatedness among Mycobacterium abscessus subsp. massiliense strains from widely separated outbreaks. Emerg. Infect. Dis. 20, 364-371.

Kimaro Mlacha S.Z., Romero-Steiner S., Dunning Hotopp J.C., Kumar N., Ishmael N., Riley D.R., Farooq U., Creasy T.H., Tallon L.J., Liu X., Goldsmith C.S., Sampson J., Carlone G.M., Hollingshead S.K., Scott J.A.G., and Tettelin H. (2013) Phenotypic, genomic, and transcriptional characterization of Streptococcus pneumoniae interacting with human pharyngeal cells. BMC Genomics 14, 383.

Kimaro Mlacha S.Z., Peret T.C., Kumar N., Romero-Steiner S., Dunning Hotopp J.C., Ishmael N., Grinblat-Huse V., Riley D.R., Erdman D.D., Carlone G.M., Sampson J., Scott J.A.G., and Tettelin H. (2013) Transcriptional adaptation of pneumococci and human pharyngeal cells in the presence of a virus infection. BMC Genomics 14, 378.

Riley D.R., Angiuoli S.V., Crabtree J., Dunning Hotopp J.C., and Tettelin H. (2012) Using Sybil for interactive comparative genomics of microbes on the web. Bioinformatics 28, 160-166. Epub 2011 Nov 24.

Bessen D.E., Kumar N., Hall G.S., Riley D.R., Luo F., Lizano S., Ford C.N., McShan W.M., Nguyen S.V., Dunning Hotopp J.C., and Tettelin H. (2011) Whole genome association study on tissue tropism phenotypes in group A Streptococcus. J. Bacteriol. 193, 6651-6663. Epub 2011 Sep 23.

Budroni S., Siena E., Dunning Hotopp J.C., Seib K.L., Serruto D., Nofroni C., Comanducci M., Riley D.R., Daugherty S.C., Angiuoli S.V., Covacci A., Pizza M., Rappuoli R., Moxon R., Tettelin H.*, and Medini D.* [*These authors have contributed equally to this work] (2011) Neisseria meningitidis is structured in clades associated with restriction modification systems that modulate homologous recombination. Proc. Natl. Acad. Sci. USA 108, 4494-4499. Epub 2011 Feb 28.

Tettelin H., Masignani M., Cieslewicz M.J., Donati C., Medini D., Ward N.L., Angiuoli S.V., Crabtree J., Jones A., Durkin A.S., DeBoy R.T., Davidsen T.M., Mora M., Scarselli M., Margarit y Ros I., Peterson J.D., Hauser C.R., Sundaram J.P., Nelson W.C., Madupu R., Brinkac L.M., Dodson R.J., Rosovitz M.J., Sullivan S.A., Daugherty S.C., Haft D.H., Selengut J., Gwinn M.L., Zhou L., Zafar N., Khouri H., Radune D., Dimitrov G., Watkins K., O'Connor K.J.B., Smith S., Utterback T.R., White O., Rubens C.E., Grandi G., Madoff L.C., Kasper D.L., Telford J.L., Wessels M.R., Rappuoli R., and Fraser C.M. (2005) Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: implications for the microbial "pan-genome." Proc. Natl. Acad. Sci. USA 102, 13950-13955. Erratum in: Proc. Natl. Acad. Sci. USA102, 16530. Featured in Nature Reviews Microbiology. Featured in The Scientist.

Tettelin H., Nelson K.E., Paulsen I.T., Eisen J.A., Read T.D., Peterson S., Heidelberg J., DeBoy R.T., Haft D.H., Dodson R.J., Durkin A.S., Gwinn M., Kolonay J.F., Nelson W.C., Peterson J.D., Umayam L.A., White O., Salzberg S.L., Lewis M.R., Radune D., Holtzapple E., Khouri H., Wolf A.M., Utterback T.R., Hansen C.L., McDonald L.A., Feldblyum T.V., Angiuoli S., Dickinson T., Hickey E.K., Holt I.E., Loftus B.J., Yang F., Smith H.O., Venter J.C., Dougherty B.A., Morrison D.A., Hollingshead S.K., and Fraser C.M. (2001) Complete genome sequence of a virulent isolate of Streptococcus pneumoniae. Science 293, 498-506. Fast Breaking Paper. Hot paper 1. Hot paper 2.

Tettelin H., Saunders N.J., Heidelberg J., Jeffries A.C., Nelson K.E., Eisen J.A., Ketchum K.A., Hood D.W., Peden J.F., Dodson R.J., Nelson W.C., Gwinn M.L., DeBoy R., Peterson J.D., Hickey E.K., Haft D.H., Salzberg S.L., White O., Fleischmann R.D., Dougherty B.A., Mason T., Ciecko A., Parksey D.S., Blair E., Cittone H., Clark E.B., Cotton M.D., Utterback T.R., Khouri H., Qin H., Vamathevan J., Gill J., Scarlato V., Masignani V., Pizza M., Grandi G., Sun L., Smith H.O., Fraser C.M., Moxon E.R., Rappuoli R., and Venter J.C. (2000) Complete genome sequence of Neisseria meningitidis serogroup B strain MC58. Science 287, 1809-1815. Hot Paper in The Scientist.

 

Complete list of publications in reverse chronological order

 

Skov Sørensen U.B., Yao K., Yang Y., Tettelin H., and Kilian M. (2016) Capsular polysaccharide expression in commensal Streptococcus species: genetic and antigenic similarities with Streptococcus pneumoniae. mBio 7, e01844-16. doi: 10.1128/mBio.01844-16.

Siena E., D’Aurizio R., Riley D., Tettelin H., Guidotti S., Torricelli G., Moxon E.R., and Medini D. (2016) In-silico prediction and deep-DNA sequencing validation indicate phase variation in 115 Neisseria meningitidis genes. BMC Genomics 17, 843. doi: 10.1186/s12864-016-3185-1.

Blanchette K.A., Shenoy A.T., Milner II J., Gilley R.P., McClure E., Hinojosa C.A., Kumar N., Daugherty S.C., Tallon L.J., Ott S., King S.J., Ferreira D.M., Gordon S.B., Tettelin H., and Orihuela C.J (2016) Neuraminidase-exposed galactose promotes Streptococcus pneumoniae biofilm formation during colonization. Infect. Immun. 84, 2922-2932. doi: 10.1128/IAI.00277-16.

Hooven T.A., Catomeris A.J., Akabas L.H., Randis T.M., Maskell D.J., Peters S.E., Ott S., Santana-Cruz I., Tallon L.J., Tettelin H., and Ratner A.J. (2016) The essential genome of Streptococcus agalactiae. BMC Genomics 17, 406. doi: 10.1186/s12864-016-2741-z.

Park I.K., Hsu A.P., Tettelin H., Shallom S., Drake S.K., Ding L., Wu U.I., Adamo N., Prevots D.R., Olivier K.N., Holland S.M., Sampaio E.P., and Zelazny A.M. (2015) Clonal diversification and changes in lipid traits and colony morphology in Mycobacterium abscessusclinical isolates. J. Clin. Microbiol. 3, 3438-3447. doi: 10.1128/JCM.02015-15.

Szymanski E.P., Leung J.M., Fowler C.J., Haney C., Hsu A.P., Chen F., Duggal P., Oler A.J., McCormack R., Podack E., Drummond R.A., Lionakis M.S., Browne S.K., Prevots D.R., Knowles M., Cutting G., Liu X., Devine S.E., Fraser C.M., Tettelin H., Olivier K.N., Holland S.M. (2015) Pulmonary nontuberculous mycobacterial infection: a multisystem multigenic disease. Am. J. Respir. Crit. Care Med. 192, 618-628 doi: 10.1164/rccm.201502-0387OC.

Tettelin H., Chancey S., Mitchell T., Denapaite D., Schähle Y., Rieger M., and Hakenbeck R. (2015) Genomics, genetic variation, and regions of differences. In Streptococcus pneumoniae: Molecular Mechanisms of Host-Pathogen Interactions, pp. 81-107, Brown J., Hammerschmidt S, and Orihuela C. Eds, Academic Press (San Diego, CA, USA).

Le Breton Y., Belew A.T., Valdes K.M., Islam E., Curry P., Tettelin H., Shirtliff M.E., El-Sayed N.M., and McIver K.S. (2015) Essential genes in the core genome of the human pathogen Streptococcus pyogenes. Sci. Rep. 5, 9838. doi: 10.1038/srep09838.

Rosini R., Campisi E., De Chiara M., Tettelin H., Rinaudo D., Toniolo C., Metruccio M., Guidotti S., Skov Sørensen U.B., Kilian M., DEVANI Consortium, Ramirez M., Janulczyk R., Donati C., Grandi G., and Margarit I. (2015) Genomic analysis reveals the molecular basis for capsule loss in group B Streptococcus population. PLoS One 10, e0125985. doi:10.1371/journal.pone.0125985.

Chancey S.T., Agrawal S., Schroeder M.R., Farley M.M., Tettelin H.*, and Stephens D.S.* [*These authors have contributed equally to this work] (2015) Composite mobile genetic elements disseminating macrolide resistance in Streptococcus pneumoniae. Front. Microbiol. 6, 26. doi: 10.3389/fmicb.2015.00026.

Chancey S.T., Bai X., Kumar N., Drabek E.F., Daugherty S.C., Colon T., Ott S., Sengamalay N., Sadzewicz L., Tallon L.J., Fraser C.M.,Tettelin H. and Stephens D.S. (2015) Transcriptional attenuation controls macrolide inducible efflux and resistance in Streptococcus pneumoniae and in other Gram-positive bacteria containing mef/mel(msr(D)) elements. PLoS One 10, e0116254. doi: 10.1371/journal.pone.0116254.

Vernikos G., Medini D., Riley D.R., and Tettelin H. (2015) Ten years of pan-genome analyses. Curr. Opin. Microbiol. 23, 148-154.

Hooven T.A., Randis T.M., Daugherty S.C., Narechania A., Planet P.J., Tettelin H.*, and Ratner A.J.* [*These authors have contributed equally to this work] (2014) Complete genome sequence of Streptococcus agalactiae strain CNTC 10/84, a hypervirulent sequence type 26 strain. Genome Announc. 2, e01338-14. doi:10.1128/genomeA.01338-14.

Bessen D.E., McShan W.M., Nguyen S.V., Shetty A., Agrawal S., and Tettelin H. (2014) Molecular epidemiology and genomics of group A Streptococcus. Infect. Genet. Evol. (MEEGID). pii: S1567-1348(14)00382-7. doi: 10.1016/j.meegid.2014.10.011.

Kilian M., Riley D.R., Jensen A., Brüggemann H., and Tettelin H. (2014) Parallel evolution of Streptococcus pneumoniae andStreptococcus mitis to pathogenic and mutualistic lifestyles. mBio 5, e01490-14. doi:10.1128/mBio.01490-14.

Dugan V.G., Emrich S.J., Giraldo-Calderón G.I., Harb O.S., Newman R.M., Pickett B.E., Schriml L.M., Stockwell T.B., Stoeckert C.J. Jr, Sullivan D.E., Singh I., Ward D.V., Yao A., Zheng J., Barrett T., Birren B., Brinkac L., Bruno V.M., Caler E., Chapman S., Collins F.H., Cuomo C.A., Di Francesco V., Durkin S., Eppinger M., Feldgarden M., Fraser C.M., Fricke W.F., Giovanni M., Henn M.R., Hine E., Dunning Hotopp J., Karsch-Mizrachi I., Kissinger J.C., Lee E.M., Mathur P., Mongodin E.F., Murphy C.I., Myers G., Neafsey D.E., Nelson K.E., Nierman W.C., Puzak J., Rasko D., Roos D.S., Sadzewicz L., Silva J.C., Sobral B., Squires R.B., Stevens R.L., Tallon L., Tettelin H., Wentworth D., White O., Will R., Wortman J., Zhang Y., Scheuermann R.H. (2014) Standardized metadata for human pathogen/vector genomic sequences. PLoS One 9, e99979. doi: 10.1371/journal.pone.0099979.

Tettelin H., Davidson R.M., Agrawal S., Aitken M., Shallom S., Hasan N.A., Strong M., Calado Nogueira de Moura V., De Groote M.A., Duarte R.S., Hine E., Parankush S., Su Q., Daugherty S.C., Fraser C.M., Brown-Elliott B.A., Wallace Jr. R.J., Holland S.M., Sampaio E.P., Olivier K.N., Jackson M., and Zelazny A.M. (2014) High-level relatedness among Mycobacterium abscessus subsp. massiliense strains from widely separated outbreaks. Emerg. Infect. Dis. 20, 364-371.

Zubair S., de Villiers E.P., Younan M., Andersson G., Tettelin H., Riley D.R., Jores J., Bongcam-Rudloff E., and Bishop R.P. (2013) Genome sequences of two pathogenic Streptococcus agalactiae isolates from the one-humped camel Camelus dromedarius. Genome Announc. 1, e00515-13.

Shallom S.J., Gardina P.J., Myers T.G., Sebastian Y., Conville P., Calhoun L.B., Tettelin H., Olivier K.N., Uzel G., Sampaio E.P., Holland S.M., and Zelazny A.M. (2013) New rapid scheme for distinguishing subspecies of the Mycobacterium abscessus group and identification of Mycobacterium massiliense with inducible clarithromycin resistance. J. Clin. Microbiol. 51, 2943-2949. Epub 2013 Jun 26.

Kimaro Mlacha S.Z., Romero-Steiner S., Dunning Hotopp J.C., Kumar N., Ishmael N., Riley D.R., Farooq U., Creasy T.H., Tallon L.J., Liu X., Goldsmith C.S., Sampson J., Carlone G.M., Hollingshead S.K., Scott J.A.G., and Tettelin H. (2013) Phenotypic, genomic, and transcriptional characterization of Streptococcus pneumoniae interacting with human pharyngeal cells. BMC Genomics 14, 383.

Kimaro Mlacha S.Z., Peret T.C., Kumar N., Romero-Steiner S., Dunning Hotopp J.C., Ishmael N., Grinblat-Huse V., Riley D.R., Erdman D.D., Carlone G.M., Sampson J., Scott J.A.G., and Tettelin H. (2013) Transcriptional adaptation of pneumococci and human pharyngeal cells in the presence of a virus infection. BMC Genomics 14, 378.

Klinzing D.C., Ishmael N., Dunning Hotopp J.C., Tettelin H., Shields K.R., Madoff L.C., and Puopolo K.M. (2013) The two-component response regulator LiaR regulates cell wall stress responses, pili expression, and virulence in group B Streptococcus. Microbiology 159,1521-1534. Epub 2013 May 23.

Le Breton Y., Mistry P., Valdes K., Quigley J., Kumar N., Tettelin H., and McIver K. (2013) Genome-wide identification of genes required for fitness of the group A Streptococcus in human blood. Infect. Immun. 81, 862-875. Epub 2013 Jan 7.

Tettelin H., Sampaio E.P., Daugherty S., Hine E., Riley D.R., Sadzewicz L., Sengamalay N., Shefchek K., Su Q., Tallon L.J., Conville P., Olivier K., Holland S.M., Fraser C.M., and Zelazny A.M. (2012) Genomic insights into the emerging human pathogen Mycobacterium massiliense. J. Bacteriol. (Genome Announcement) 194, 5450.

Krauland M.G., Dunning Hotopp J.C., Riley D.R., Daugherty S.C., Marsh J.W., Messonier N.E., Mayer L.W., Tettelin H., and Harrison L.H. (2012) Whole genome sequencing to investigate the emergence of clonal complex 23 Neisseria meningitidis serogroup Y disease in the United States. PLoS One 7, e35699. Epub 2012 Apr 27.

Brüggemann H., Lomholt H.B., Tettelin H., and Kilian M. (2012) CRISPR/cas loci of type II Propionibacterium acnes confer immunity against acquisition of mobile elements present in type I P. acnes. PLoS One 7, e34171. Epub 2012 Mar 30.

Riley D.R., Angiuoli S.V., Crabtree J., Dunning Hotopp J.C., and Tettelin H. (2012) Using Sybil for interactive comparative genomics of microbes on the web. Bioinformatics 28, 160-166. Epub 2011 Nov 24.

Hiller N.L., Eutsey R.A., Powell E., Earl J., Janto B., Martin D., Dawid S., Ahmed A., Longwell M., Dahlgreen M., Ezzo S., Tettelin H., Daugherty S.C., Mitchell T., Hillman T., Buchinsky F., Tomasz A., de Lencastre H., Sá-Leão R., Post J.C., Hu F.Z., and Ehrlich G.D. (2011) Differences in genotype and virulence among four multidrug-resistant Streptococcus pneumoniae isolates belonging to the PMEN1 clone. PLoS One 6, e28850. Epub 2011 Dec 19.

Sanchez C.J., Kumar N., Lizcano A., Shivshankar P., Dunning Hotopp J.C., Jorgensen J.H., Tettelin H., and Orihuela C.J. (2011) Streptococcus pneumoniae in biofilms are unable to cause invasive disease due to altered virulence determinant production. PLoS One 6, e28738. Epub 2011 Dec 8.

Tettelin H. and Kilian M. (2011) Genomes of Streptococcus mitis, Streptococcus oralis, and Streptococcus infantis. In Oral Microbial Communities: Genomic Inquiry and Interspecies Communication, pp. 37-42, Kolenbrander P.E. Ed., ASM Press (Washington, DC, USA).

Poulsen K., Tettelin H. and Kilian M. (2011) The Aggregatibacter actinomycetemcomitans genome: diversity of pathogenic potential. In Oral Microbial Communities: Genomic Inquiry and Interspecies Communication, pp. 103-117, Kolenbrander P.E. Ed., ASM Press (Washington, DC, USA).

Bessen D.E., Kumar N., Hall G.S., Riley D.R., Luo F., Lizano S., Ford C.N., McShan W.M., Nguyen S.V., Dunning Hotopp J.C., and Tettelin H. (2011) Whole genome association study on tissue tropism phenotypes in group A Streptococcus. J. Bacteriol. 193, 6651-6663. Epub 2011 Sep 23.

Lee A.W., Tettelin H., and Chancey S. (2011) Genomic analyses of clonal isolates provide clues to the evolution of Streptococcus pneumoniae (Commentary). Front. Microbio. 2, 63.

Angiuoli S.V., Dunning Hotopp J.C., Salzberg S.L., and Tettelin H. (2011) Improving pan-genome annotation using whole genome multiple alignment. BMC Bioinformatics 12, 272.

Budroni S., Siena E., Dunning Hotopp J.C., Seib K.L., Serruto D., Nofroni C., Comanducci M., Riley D.R., Daugherty S.C., Angiuoli S.V., Covacci A., Pizza M., Rappuoli R., Moxon R., Tettelin H.*, and Medini D.* [*These authors have contributed equally to this work] (2011) Neisseria meningitidis is structured in clades associated with restriction modification systems that modulate homologous recombination. Proc. Natl. Acad. Sci. USA 108, 4494-4499. Epub 2011 Feb 28.

Donati C., Hiller N.L., Tettelin H., Muzzi A., Croucher N.J., Angiuoli S.V., Oggioni M., Dunning Hotopp J.C., Hu F.Z., Riley D., Covacci A., Mitchell T.J., Bentley S.D., Kilian M., Ehrlich G.D., Rappuoli R., Moxon E.R., and Masignani V. (2010) Structure and dynamics of the pan-genome of Streptococcus pneumoniae and closely related species. Genome Biol. 11, R107.

Bottacini F., Medini D., Pavesi A., Turroni F., Foroni E., Riley D., Giubellini D., Tettelin H., van Sinderen D., and Ventura M. (2010) Comparative genomics of the genus Bifidobacterium. Microbiology 156, 3243-3254. Epub 2010 Jul 15.

Janulczyk R., Masignani V., Maione D., Tettelin H., Grandi G., and Telford J. (2010) Simple sequence repeats and genome plasticity inStreptococcus agalactiae. J. Bacteriol. 192, 3990-4000. Epub 2010 May 21.

Gomes Moriel D., Bertoldi I., Spagnuolo A., Marchi S., Rosini R., Nesta B., Pastorello I., Mariani Corea V.A., Torricelli G., Cartocci E., Savino S., Scarselli M., Dobrindt U., Hacker J., Tettelin H., Tallon L.J., Sullivan S., Wieler L.H., Ewerse C., Pickard D., Dougan G., Rita Fontana M., Rappuoli R., Pizza M., and Serino L. (2010) Identification of protective and broadly conserved vaccine antigens from the genome of extraintestinal pathogenic Escherichia coli. Proc. Natl. Acad. Sci. USA 107, 9072-9077. Epub 2010 May 3.

van Schaik W., Top J., Riley D.R., Boekhorst J., Vrijenhoek J.E., Schapendonk C.M., Hendrickx A.P., Nijman I.J., Bonten M.J., Tettelin H., and Willems R.J. (2010) Pyrosequencing-based comparative genome analysis of the nosocomial pathogen Enterococcus faeciumand identification of a large transferable pathogenicity island. BMC Genomics 11, 239. Epub 2010 Apr 14.

Schoen C., Tettelin H., Parkhill J., and Frosch M. (2009) Genome flexibility in Neisseria meningitidis. Vaccine 27 supplement 2, B103-B111. Epub 2009 June 24.

Ishmael N., Dunning Hotopp J.C., Ioannidis P., Biber S., Sakamoto J., Siozios S., Nene V., Werren J., Bourtzis K., Bordenstein S.R.,Tettelin H. (2009) Extensive Genomic Diversity of Closely Related Wolbachia Strains. Microbiology 155, 2211-2222. Epub 2009 Apr 23.

Bordenstein S.R., Paraskevopoulos C., Dunning Hotopp J.C., Sapountzis P., Lo N., Bandi C., Tettelin H., Werren J.H., and Bourtzis K. (2009) Parasitism and mutualism in Wolbachia: what the phylogenomic trees can and can not say. Mol. Biol. Evol. 26, 231-241. Epub 2008 Oct. 28.

Tettelin H. and Feldblyum T. (2009) Bacterial genome sequencing. In Methods in Molecular Biology 551: Molecular Epidemiology of Microorganisms, pp. 231-247, Caugant D.A. Ed., Humana Press Inc. (Clifton, NJ, USA).

Tettelin H. (2009) The bacterial pan-genome and reverse vaccinology. In Genome Dynamics 6: Microbial Pathogenomics, pp. 35-47, de Reuse H. and Bereswill S. Eds, Karger (Basel, Switzerland). DOI: 10.1159/000235761.

Kilian M., Poulsen K., Blomqvist T., Håvarstein L.S., Bek-Thomsen M., Tettelin H., and Sørensen U.B.S. (2008) Evolution of Streptococcus pneumoniae and its close commensal relatives. PLoS ONE 3(7), e2683, doi:10.1371/journal.pone.0002683.

Tettelin H., Riley D., Cattuto C., and Medini D. (2008) Comparative genomics: the bacterial pan-genome. Curr. Opin. Microbiol. 11: 472-477, doi:10.1016/j.mib.2008.09.006.

Valdes J., Pedroso I., Quatrini R., Dodson R.J., Tettelin H., Blake R. II, Eisen J.A., and Holmes, D.S. (2008) Acidithiobacillus ferrooxidans metabolism: from genome sequence to industrial applications. BMC Genomics 9, 597, doi:10.1186/1471-2164-9-597. PMCID: PMC2621215.

Bek-Thomsen M., Tettelin H., Hance I., Nelson K.E., and Kilian M. (2008) Population diversity and dynamics of Streptococcus mitis,Streptococcus oralis and Streptococcus infantis in the upper respiratory tract of adults determined by a non-culture strategy. Infect. Immun., 76, 1889-1896. Epub 2008 Mar 3.

Jiang S.-M., Ishmael N., Dunning Hotopp J., Puliti M., Tissi 3., Kumar n., Cieslewicz M.J., Tettelin H., and Wessels M.R. (2008) Variation in the group B Streptococcus CsrRS regulon and effects on pathogenicity. J. Bacteriol. 190, 1956-1965. Epub 2008 Jan. 18.

Masignani V., Tettelin H., and Rappuoli R. (2007) Vaccines against infectious diseases: a biotechnology-driven evolution. In Genomic and Personalized Medicine, Willard H.F. and Ginsburg G.S. Eds, Elsevier/Academic Press (San Diego, CA, USA), vol. 1; pp: 562-570.

Raghavan N., Tettelin H., Miller A., Hostetler J., Tallon L., and Knight M. (2007) Nimbus (BgI): An active non-LTR retrotransposon of theSchistosoma mansoni snail host Biomphalaria glabrata. Int. J. Parasitol. 37, 1307-1318. Epub 2007 Apr. 19.

Dunning Hotopp J.C., Clark M.E., Oliveira D.C.S.G., Foster J.M., Fischer P., Mun~oz Torres M.C., Giebel J.D., Kumar N., Ishmael N., Wang S., Ingram J., Nene R.V., Shepard J., Tomkins J., Richards S., Spiro D.J., Ghedin E., Slatko B.E., Tettelin H.*, and Werren J. H.* [*These authors have contributed equally to this work] (2007) Widespread lateral gene transfer from intracellular bacteria to multicellular eukaryotes. Science 317, 1753-1756. Epub 2007 Aug. 30.

Tettelin H., Rappuoli R., and Fraser-Liggett C.M. (2007) Using genomics to identify novel vaccine candidates against pathogens. In The Jordan Report, Accelerated Development of Vaccines 2007, U.S. Department of Health and Human Services, pp. 37-42.

Myers G.S.A., Parker D., Al-Hasani K., Kennan R.M., Seemann T., Ren Q., Badger J.H., Selengut J.D., DeBoy R.T., Tettelin H., Boyce J.D., McCarl V.P., Han X., Nelson W., Madupu R., Mohamoud Y., Holley T., Fedorova N., Khouri H., Bottomley S.P, Whittington R.J., Adler B., Songer J.G., Rood J.I., and Paulsen I.T. (2007) Genome sequence and identification of candidate vaccine antigens from the animal pathogen Dichelobacter nodosus. Nat. Biotechnol. 25, 569-575.

Lanie J.A., Ng W-L, Kazmierczak K.M., Andrzejewski T.M., Davidsen T.M., Wayne K.J., Tettelin H., Glass J.I., and Winkler M. (2006) Genome sequence of Avery's virulent serotype 2 strain D39 of Streptococcus pneumoniae and comparison with that of unencapsulated laboratory strain R6. J. Bacteriol. 189, 38-51.

Tettelin H., Medini D., Donati C., and Masignani V. (2006) Towards a universal group B Streptococcus vaccine using multi-strain genome analysis. Expert Rev. Vaccines 5, 687-694.

Dunning Hotopp J.C., Grifantini R., Kumar N., Tzeng Y.L., Fouts D., Frigimelica E., Draghi M., Giuliani M.M., Rappuoli R., Stephens D.S., Grandi G., and Tettelin H. (2006) Comparative genomics of Neisseria meningitidis: core genome, islands of horizontal transfer and pathogen specific genes. Microbiology 152, 3733-3749. Featured in Microbiology Today.

Savard J., Tautz D., Richards S., Weinstock G.M., Gibbs R.A., Werren J.H., Tettelin H., and Lercher M.J. (2006) Phylogenomic analysis reveals bees and wasps (Hymenoptera) at the base of the radiation of holometabolous insects. Genome Res. 16, 1334-1338.

Baldo L., Dunning Hotopp J.C., Jolley K.A., Bordenstein S.R., Biber S.A., Choudhury R.R., Hayashi C., Maiden M.C.J., Tettelin H., and Werren J.H. (2006) A multilocus sequence typing system for the endosymbiont Wolbachia. Appl. Environ. Microbiol. 72, 7098-7110.

Ramaswamy S.V., Ferrieri P., Madoff L.C., Flores A.E., Kumar N., Tettelin H., and Paoletti L.C. (2006) Identification of novel cps locus polymorphisms in nontypeable group B Streptococcus. J. Med. Microbiol. 55, 775-783.

Dunning Hotopp J.C., Lin M., Madupu R., Crabtree J., Angiuoli S.V., Eisen J., Seshadri R., Ren Q., Wu M., Utterback T.R., Smith S., Lewis M.R., Khouri H., Zhang C., Hua N., Lin Q., Ohashi N., Zhi N., Nelson W., Brinkac L.M., Dodson R.J., Rosovitz M.J., Sundaram J., Daugherty S.C., Davidsen T., Durkin A.S., Gwinn M.L., Haft D.H., Selengut J.D., Sullivan S.A., Zafar N., Zhou L., Benahmed F., Forberger H., Halpin R., Mulligan S., Robinson J., White O., Rikihisa Y., and Tettelin H. (2006) Comparative genomics of emerging human ehrlichiosis agents. PLoS Genet. 2, e21. Featured in Nature Reviews Microbiology.

Medini D., Donati C., Tettelin H., Masignani V., and Rappuoli R. (2005) The microbial pan-genome. Curr. Opin. Genet. Dev. 15, 589-594.

Tettelin H., Masignani M., Cieslewicz M.J., Donati C., Medini D., Ward N.L., Angiuoli S.V., Crabtree J., Jones A., Durkin A.S., DeBoy R.T., Davidsen T.M., Mora M., Scarselli M., Margarit y Ros I., Peterson J.D., Hauser C.R., Sundaram J.P., Nelson W.C., Madupu R., Brinkac L.M., Dodson R.J., Rosovitz M.J., Sullivan S.A., Daugherty S.C., Haft D.H., Selengut J., Gwinn M.L., Zhou L., Zafar N., Khouri H., Radune D., Dimitrov G., Watkins K., O'Connor K.J.B., Smith S., Utterback T.R., White O., Rubens C.E., Grandi G., Madoff L.C., Kasper D.L., Telford J.L., Wessels M.R., Rappuoli R., and Fraser C.M. (2005) Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: implications for the microbial "pan-genome." Proc. Natl. Acad. Sci. USA 102, 13950-13955. Erratum in: Proc. Natl. Acad. Sci. USA102, 16530. Featured in Nature Reviews Microbiology. Featured in The Scientist.

Maione D., Margarit I., Rinaudo C.D., Masignani V., Mora M., Scarselli M., Tettelin H., Brettoni C., Iacobini E.T., Rosini R., D'Agostino N., Miorin L., Buccato S., Mariani M., Galli G., Nogarotto R., Nardi Dei G., Vegni F., Fraser C.M., Mancuso G., Teti G., Madoff L.C., Paoletti L.C., Rappuoli R., Kasper D.L., Telford J.L., and Grandi G. (2005) Identification of a universal Group B Streptococcus vaccine by multiple genome screen. Science 309, 148-150. Featured in The Scientist.

Tettelin H. (2004) Streptococcal genomes provide food for thought (News and Views). Nat. Biotechnol. 22, 1523-1524.

Ward N., Larsen Ø., Sakwa J., Bruseth L., Khouri H., Durkin A.S., Dimitrov G., Jiang L., Scanlan D., Kang K., Lewis M., Nelson K.E., Methé B., Wu M., Heidelberg J.F., Paulsen I.T., Fouts D., Ravel J., Tettelin H., Ren Q., Read T., DeBoy R., Seshadri R., Salzberg S.L., Jensen H.B., Kåre Birkeland N., Nelson W., Dodson R.J., Grindhaug S.H., Holt I., Eidhammer I., Jonasen I., Vanaken S., Utterback T., Feldblyum T.V., Lillehaug J., Fraser C.M., and Eisen J.A. (2004) Genomic insights into methanotrophy: the complete genome sequence of Methylococcus capsulatus (Bath). PLoS Biol. 2, 1616-1628 [2(10): e303].

Tettelin H. and Parkhill J. (2004) The use of genome annotation data and its impact on biological conclusions (correspondence letter). Nature Genetics 36, 1028-1029.

Nierman W., DeShazer D., Kim H., Tettelin H., Nelson K, Feldblyum T., Ulrich R., Ronning C., Brinkac L., Daugherty S., Davidsen T., DeBoy R., Dimitrov G., Dodson R., Durkin S., Gwinn M., Haft D., Khouri H., Kolonay J., Madupu R., Mohammoud Y., Nelson W., Radune D., Romero C., Sarria S., Selengut J., Shamblin C., Sullivan S., White O., Yu Y., Zafar N., Zhou L., and Fraser C.M. (2004) Structural Flexibility in the Burkholderia mallei Genome. Proc. Natl. Acad. Sci. USA 101, 14246-14251.

Tettelin H. and Hollingshead S.K. (2004) Comparative genomics of S. pneumoniae: intra-strain diversity and genome plasticity. In The pneumococcus, pp. 15-29, Tuomanen E., Mitchell T., Morrison D. and Spratt B. Eds. ASM Press (Washington, DC, USA).

Seshadri R., Myers G.S.A., Tettelin H., Eisen J.A., Heidelberg J.F., Davidsen T.M., Dodson R.J., Deboy R.T., Fouts D.E., Haft D.H., Selengut J., Ren Q., Brinkac L.M., Madupu R., Kolonay J.F., Durkin A.S., Daugherty S.C., Shetty J., Shvartsbeyn A., Gebregeorgis E., Geer K., Tsegaye G., Malek J., Ayodeji B., Shatsman S., McLeod M.P., Majs D., Howell J.K., Pal S., Amin A., Vashisth P., McNeill T.Z., Weinstock G.M., Norris S.J., Fraser C.M., and Paulsen I.T. (2004) Comparison of the genome of the oral pathogen, Treponema denticola, with other spirochete genomes. Proc. Natl. Acad. Sci. USA 101, 5646-5651.

Wu M., Sun L.V., Vamathevan J., Riegler M., DeBoy R., Brownlie J.C., McGraw E.A., Martin W., Esser C., Ahmadinejad N., Wiegand C., Madupu R., Beanan M.J., Brinkac L.M., Daugherty S.C., Durkin A.S., Kolonay J.F., Nelson W.C., Mohamoud Y., Lee P., Berry K., Young M.B., Utterback T., Weidman J., Nierman W.C., Paulsen I.T., Nelson K.E., Tettelin H., O'Neill S.L., and Eisen J.A. (2004) Phylogenomics of the reproductive parasite Wolbachia pipientis wMel: a streamlined genome overrun by mobile genetic elements. PLoS Biol. 2: 327-341.

Radune D. and Tettelin H. (2004) Optimized multiplex polymerase chain reaction, an effective method for rapid gap closure. In Methods in Molecular Biology 255: Bacterial Artificial Chromosomes, pp. 309-318, Zhao S. and Stodolsky M. Eds, Humana Press Inc. (Totowa, NJ, USA).

Tettelin H. and Feldblyum T. (2004) Genome sequencing and analysis. In Genomics, Proteomics and Vaccines, pp. 45-73, Grandi G. Ed., John Wiley and Sons Ltd (London, United Kingdom).

Telford J.L., Margarit y Ros I., Maione D., Masignani V., Tettelin H., Bensi G., and Grandi G. (2004) Vaccines against pathogenic streptococci. In Genomics, Proteomics and Vaccines, pp. 205-222, Grandi G. Ed., John Wiley and Sons Ltd (London, United Kingdom).

Nelson K.E., Fleischmann R.D., DeBoy R.T., Paulsen I.T., Fouts D.E., Eisen J.A., Daugherty S.C., Dodson R.J., Durkin A.S., Gwinn M., Haft D.H., Kolonay J.F., Nelson W.C., Mason T., Tallon L., Gray J., Granger D., Tettelin H., Dong H., Galvin J.L., Duncan M.J., Dewhirst F.E., and Fraser C.M. (2003) Complete genome sequence of the oral pathogenic bacterium Porphyromonas gingivalis strain W83. J. Bacteriology 185, 5591-5601.

Read T.D., Peterson S.N., Tourasse N., Baillie L.W., Paulsen I.T., Nelson K.E., Tettelin H., Fouts D.E., Eisen J.A., Gill S.R., Holtzapple E.K., Økstad O.A., Helgason E., Rilstone J., Wu M., Kolonay J.F., Beanan M.J., Dodson R.J., Brinkac L.M., Gwinn M., DeBoy R.T., Madupu R., Daugherty S.C., Durkin A.S., Haft D.H., Nelson W.C., Peterson J.D., Pop M., Khouri H.M., Radune D., Benton J.L., Mahamoud Y., Jiang L., Hance I.R., Weidman J.F., Berry K.J., Plaut R.D., Wolf A.M., Watkins K.L., Nierman W.C., Hazen A., Cline R., Redmond C., Thwaite J.E., White O., Salzberg S.L., Thomason B., Friedlander A.M., Koehler T.M., Hanna P.C., Kolstø A-B., and Fraser C.M. (2003) The genome sequence of Bacillus anthracis Ames and comparison to closely related bacteria. Nature 423, 81-86.

Seshadri R., Paulsen I.T., Eisen J.A., Read T.D., Nelson K.E., Nelson W.C., Ward N.L., Tettelin H., Davidsen T.M., Beanan M.J., Deboy R.T., Daugherty S.C., Brinkac L.M., Madupu R., Dodson R.J., Khouri H.M., Lee K.H., Carty H.A., Scanlan D., Heinzen R.A., Thompson H.A., Samuel J.E., Fraser C.M., and Heidelberg J.F. (2003) Complete genome sequence of the Q-fever pathogen Coxiella burnetii. Proc. Natl. Acad. Sci. USA 100, 5455-5460.

Paulsen I.T., Banerjei L., Myers G.S.A., Nelson K.E., Seshadri R., Read T.D., Fouts D.E., Eisen J.A., Gill S.R., Heidelberg J.F., Tettelin H.,Dodson R.J., Umayam L., Brinkac L., Beanan M., Daugherty S., DeBoy R.T., Durkin S., Kolonay J., Madupu R., Nelson W., Vamathevan J., Tran B., Upton J., Hansen T., Shetty J., Khouri H., Utterback T., Radune D., Ketchum K.A., Dougherty B.A., and Fraser C.M. (2003) Role of mobile DNA in the evolution of vancomycin-resistant Enterococcus faecalis. Science 299, 2071-2074.

Paulsen I.T., Seshadri R., Nelson K.E., Eisen J.A., Heidelberg J.F., Read T.D., Dodson R.J., Umayam L., Brinkac L.M., Beanan M.J., Daugherty S.C., Deboy R.T., Durkin A.S., Kolonay J.F., Madupu R., Nelson W.C., Ayodeji B., Kraul M., Shetty J., Malek J., Van Aken S.E., Riedmuller S., Tettelin H., Gill S.R., White O., Salzberg S.L., Hoover D.L., Lindler L.E., Halling S.M., Boyle S.M., and Fraser C.M. (2002) The Brucella suis genome reveals fundamental similarities between animal and plant pathogens and symbionts. Proc. Natl. Acad. Sci. USA 99: 13148-13153.

Tettelin H., Masignani V., Cieslewicz M.J., Eisen J.A., Peterson S., Wessels M.R., Paulsen I.T., Nelson K.E., Margarit I., Read T.D., Madoff L.C., Wolf A.M., Beanan M.J., Brinkac L.M., Daugherty S.C., DeBoy R.T., Durkin A.S., Kolonay J.F., Madupu R., Lewis M.R., Radune D., Fedorova N.B., Scanlan D., Khouri H., Mulligan S., Carty H.A., Cline R.T., Van Aken S.E., Gill J., Scarselli M., Mora M., Iacobini E.T., Brettoni C., Galli G., Mariani M., Vegni F., Maione D., Rinaudo D., Rappuoli R., Telford J.L., Kasper D.L., Grandi G., and Fraser C.M. (2002) Complete genome sequence and comparative genomic analysis of an emerging human pathogen, serotype V Streptococcus agalactiae. Proc. Natl. Acad. Sci. USA 99: 12391-12396.

Grifantini R., Bartolini E., Muzzi A., Draghi M., Frigimelica E., Berger J., Ratti G., Petracca R., Galli G., Agnusdei M., Giuliani M.M., Santini L., Brunelli B., Tettelin H., Rappuoli R., Randazzo F., and Grandi G. (2002) Previously unrecognized vaccine candidates against Group B meningococcus identified by DNA microarrays. Nat. Biotechnol. 20: 914-921.

Eisen J.A., Nelson K.E., Paulsen I.T., Heidelberg J.F., Wu M., Dodson R.J., DeBoy R., Gwinn M.L., Nelson W.C., Haft D.H., Hickey E.K., Peterson J.D., Durkin A.S., Kolonay J.L., Yang F., Holt I., Umayam L.A., Mason T., Brenner M., Shea T.P., Parksey D., Nierman W.C., Feldblyum T.V., Hansen C.L., Craven M.B., Radune D., Vamathevan J., Khouri H., White O., Gruber T.M., Ketchum K.A., Venter J.C.,Tettelin H., Bryant D.A., and Fraser C.M. (2002) The complete genome sequence of Cholorobium tepidum TLS, a photosynthetic, anaerobic, green-sulfur bacterium. Proc. Natl. Acad. Sci. USA 90, 9509-9514.

Read T.D., Gill S.R., Tettelin H., and Dougherty B.A. (2001) Finding drug targets in microbial genomes. Drug Discovery Today 6, 887-892.

Tettelin H., Nelson K.E., Paulsen I.T., Eisen J.A., Read T.D., Peterson S., Heidelberg J., DeBoy R.T., Haft D.H., Dodson R.J., Durkin A.S., Gwinn M., Kolonay J.F., Nelson W.C., Peterson J.D., Umayam L.A., White O., Salzberg S.L., Lewis M.R., Radune D., Holtzapple E., Khouri H., Wolf A.M., Utterback T.R., Hansen C.L., McDonald L.A., Feldblyum T.V., Angiuoli S., Dickinson T., Hickey E.K., Holt I.E., Loftus B.J., Yang F., Smith H.O., Venter J.C., Dougherty B.A., Morrison D.A., Hollingshead S.K., and Fraser C.M. (2001) Complete genome sequence of a virulent isolate of Streptococcus pneumoniae. Science 293, 498-506. Fast Breaking Paper. Hot paper 1. Hot paper 2.

Masignani V., Giuliani M.M., Tettelin H., Commanducci M., Rappuoli R., and Scarlato V. (2001) A Mu-like prophage in serogroup BNeisseria meningitidis coding for surface-exposed antigens. Infection and Immunity 69, 2580-2588.

Peterson S., Cline R.T., Tettelin H., Sharov V., and Morrison D.A. (2000) Gene expression analysis of the Streptococcus pneumoniaecompetence regulons by use DNA microarrays. J. Bacteriology 182, 6192-6202.

Saunders N.J., Jeffries A.C., Peden J.F., Hood D.W., Tettelin H., Rappuoli R., and Moxon E.R. (2000) Repeat-associated phase variable genes in the complete genome sequence of Neisseria meningitidis strain MC58. Mol. Microbiol. 37, 207-215.

Heidelberg J., Eisen J.A., Nelson W.C., Clayton R., Gwinn M.L., Dodson R.J., Haft D.H., Hickey E.K., Peterson J.D., Umayam L., Gill S.R., Nelson K.E., Read T.D., Tettelin H., Richardson D., Ermolaeva M.D., Vamathevan J., Bass S., Qin H., Dragoi I., Sellers P., McDonald L., Utterback T., Fleischmann R.D., Nierman W.C., White O., Salzberg S.L., Smith H.O., Colwell R.R., Mekalanos J., Venter J.C., and Fraser C.M. (2000) DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae. Nature 406, 477-484.

Tettelin H., Saunders N.J., Heidelberg J., Jeffries A.C., Nelson K.E., Eisen J.A., Ketchum K.A., Hood D.W., Peden J.F., Dodson R.J., Nelson W.C., Gwinn M.L., DeBoy R., Peterson J.D., Hickey E.K., Haft D.H., Salzberg S.L., White O., Fleischmann R.D., Dougherty B.A., Mason T., Ciecko A., Parksey D.S., Blair E., Cittone H., Clark E.B., Cotton M.D., Utterback T.R., Khouri H., Qin H., Vamathevan J., Gill J., Scarlato V., Masignani V., Pizza M., Grandi G., Sun L., Smith H.O., Fraser C.M., Moxon E.R., Rappuoli R., and Venter J.C. (2000) Complete genome sequence of Neisseria meningitidis serogroup B strain MC58. Science 287, 1809-1815. Hot Paper in The Scientist.

Pizza M., Scarlato V., Masignani V., Giuliani M.M., Arica B., Comanducci M., Jennings G.T., Baldi L., Bartolini E., Capecchi B., Galeotti C.L., Luzzi E., Manetti R., Marchetti E., Mora M., Nuti S., Ratti G., Santini L., Savino S., Scarselli M., Storni E., Zuo P., Broeker M., Hundt E., Knapp B., Blair E., Mason T., Tettelin H., Hood D.W., Jeffries A.C., Saunders N.J., Granoff D.M., Venter J.C., Moxon E.R., Grandi G., and Rappuoli R. (2000) Whole genome sequencing to identify vaccine candidates against serogroup B meningococcus. Science 287, 1816-1820.

Tettelin H., Radune D., Kasif S., Khouri H., and Salzberg S.L. (1999) Optimized multiplex PCR: efficiently closing a whole genome shotgun sequencing project. Genomics 62, 500-507.

Salzberg S.L., Pertea M., Delcher A.L., Gardner M.J., and Tettelin H. (1999) Interpolated markov models for eukaryotic gene finding. Genomics 59, 24-31.

Gardner M.J., Tettelin H., Carucci D.J., Cummings L.M., Smith H.O., Fraser C.M., Venter J.C., and Hoffman S.L. (1999) The malaria genome sequencing project: complete sequence of P. falciparum chromosome 2. Parassitologia 41, 69-75.

Jing J., Lai Z., Aston C., Lin J., Carucci D.J., Gardner M.J., Mishra B., Anantharaman T.S., Tettelin H., Cummings L.M., Hoffman S.L., Venter J.C., and Schwartz D.C. (1999) Optical mapping of Plasmodium falciparum chromosome 2. Genome Research 9, 175-181.

Gardner M.J., Tettelin H., Carucci D.J., Cummings L.M., Aravind L., Koonin E.V., Shallom S., Mason T., Yu K., Fujii C., Pedersen J., Shen K., Jing J., Aston C., Lai Z., Schwartz D.C., Pertea M., Salzberg S., Zhou L., Sutton G.G., Clayton R.L., White O., Smith H.O., Fraser C.M., Adams M.D., Venter J.C., and Hoffman S.L. (1998) Chromosome 2 sequence of the human malaria parasite Plasmodium falciparum. Science 282, 1126-1132.

Carucci D.J., Gardner M.J., Tettelin H., Cummings L.M., Smith H.O., Adams M.D., Venter J.C., and Hoffman S.L. (1998) Sequencing the genome of Plasmodium falciparum. Current Opinion in Infectious Diseases 11, 531-534.

Carucci D.J., Gardner M.J., Tettelin H., Cummings L.M., Smith H.O., Adams M.D., Hoffman S.L., and Venter J.C. (1998) The malaria genome sequencing project. Expert Rev. Mol. Med. 1998, 1-9.

Gardner M.J., Tettelin H., Carucci D.J., Cummings L.M., Adams M.D., Smith H.O., Venter J.C., and Hoffman S.L. (1998) The malaria genome sequencing project. Protist 149, 109-112.

Tettelin H., Thierry A., Goffeau A., and Dujon B. (1998) Physical mapping of chromosomes VII and XV of Saccharomyces cerevisiae at 3.5 kb average resolution to allow their complete sequencing. Yeast 14, 601-616.

Caro L.H.P., Tettelin H., Vossen J.H., Ram A.F.J., van den Ende H., and Klis F.M. (1997) In silicio identification of glycosyl-phosphatidylinositol-anchored plasma membrane and cell wall proteins of Saccharomyces cerevisiae. Yeast 13, 1477-1489.

Tettelin H., ..., and Kleine K. (115 authors) (1997) The nucleotide sequence of Saccharomyces cerevisiae chromosome VII. Nature 387 supplement, 81-84.

Dujon B., ..., Tettelin H., ..., and Kleine K. (97 authors) (1997) The nucleotide sequence of Saccharomyces cerevisiae chromosome XV. Nature 387 supplement, 98-102.

Bussey H., ..., Tettelin H., ..., and Hani J. (124 authors) (1997) The nucleotide sequence of Saccharomyces cerevisiae chromosome XVI. Nature 387 supplement, 103-105.

Van Dyck L., Tettelin H., Purnelle B., and Goffeau A. (1997) An 18.3 kb DNA fragment from yeast chromosome VII carries four unknown open reading frames, the gene for an Asn synthetase, remnants of Ty and three tRNA genes. Yeast 13, 171-176.

Goffeau A., Barrell B.G., Bussey H., Davis R.W., Dujon B., Feldmann H., Galibert F., Hoheisel J.D., Jacq C., Johnston M., Louis E.J., Mewes H.W., Murakami Y, Philippsen P., Tettelin H., and Oliver S.G. (1996) Life with 6000 genes. Science 274, 546-567.

Tettelin H., Thierry A., Fairhead C., Perrin A., and Dujon B. (1995) In vitro fragmentation of yeast chromosomes and yeast artificial chromosomes at artificially inserted sites and applications to genome mapping. In Methods in Molecular Genetics 6, pp. 81-107. Adolph K.W. Ed., Academic Press.

Dujon B., ..., Tettelin H., ..., and Mewes H.W. (108 authors) (1994) Complete DNA sequence of yeast chromosome XI. Nature 369, 371-378.

Purnelle B., Tettelin H., Van Dyck L., Skala J., and Goffeau A. (1993) The sequence of a 17.5 kb DNA fragment on the left arm of yeast chromosome XI identifies the protein kinase gene ELM1, the DNA primase gene PRI2, a new gene encoding a putative histone and seven new open reading frames. Yeast 9, 1379-1384.

Research Interests

  1. Analysis of pathogen diversity using whole genome sequencing. I have been in the genomics field for 25 years, since the beginning of my B.Sc. in 1991. Over these 2.5 decades I have led the genome sequencing and analysis of many organisms, starting with eukaryotic chromosomes (yeast and malaria parasite) then shifting towards bacterial pathogens. I was the lead author on the first published whole genome sequences of Neisseria meningitidis (1), Streptococcus pneumoniae (2) and Streptococcus agalactiae (3). I also led the comparative analysis of intracellular pathogens causing human ehrlichiosis (4). Over time, I have made use of the rapidly evolving genome sequencing technologies, starting with classical Sanger sequencing and transitioning to next generation sequencing techniques: 454, Illumina and Pacific Biosciences. Recently, I have conducted in-depth comparative genomics analyses of isolates from the Mycobacterium abscessus group. The Mycobacterium abscessus subspecies massiliense within the M. abscessus group is increasingly recognized as an emerging bacterial pathogen and as a cause of respiratory outbreaks in cystic fibrosis centers, with evidence of transmission among patients. Whole genome sequencing identified multiple polymorphisms, mutations and indels, within serial clinical isolates collected from two patients with cystic fibrosis (see also "Translational studies: reverse vaccinology and diagnostics"). Similar mutations were observed in M. abscessus group isolates from an outbreak in the United Kingdom. The multiple genomic mutations detected, which accumulated and persisted over time, likely result from and also impact the M. massilienseresponse to host immunity, therapeutics, and/or interactions with local microbiota in the cystic fibrosis lung.
    1. Tettelin H, Saunders NJ, Heidelberg J, et al. Complete genome sequence of Neisseria meningitidis serogroup B strain MC58. Science. 2000 Mar 10;287(5459):1809-15. PubMed PMID: 10710307.
    2. Tettelin H, Nelson KE, Paulsen IT, Eisen JA, et al. Complete genome sequence of a virulent isolate of Streptococcus pneumoniae. Science. 2001 Jul 20;293(5529):498-506. PubMed PMID: 11463916.
    3. Tettelin H, Masignani V, Cieslewicz MJ, et al. Complete genome sequence and comparative genomic analysis of an emerging human pathogen, serotype V Streptococcus agalactiae. Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12391-6. PubMed PMID: 12200547; PubMed Central PMCID: PMC129455.
    4. Dunning Hotopp JC, Lin M, Madupu R, Crabtree J, Angiuoli SV, et al. Comparative genomics of emerging human ehrlichiosis agents. PLoS Genet. 2006 Feb;2(2):e21. PubMed PMID: 16482227; PubMed Central PMCID: PMC1366493.
  2. Translational studies: reverse vaccinology and diagnostics. I have a long track record of developing computational and analytical approaches to support translational efforts aimed at developing new vaccines and therapeutics. In collaboration with the team of Dr. Rino Rappuoli at GlaxoSmithKline (former Chiron Vaccines and Novartis Vaccines and Diagnostics), I leveraged bacterial genome information to pioneer the Reverse Vaccinology approach that identifies and prioritizes novel vaccine candidates using whole genome sequencing (1-3). We applied it to Neisseria meningitidis serogroup B for which no broadly protective vaccine candidates had been identified after decades of classical vaccinology. We identified all predicted surface-exposed proteins from serogroup B Neisseria in silico based on various protein motifs and these proteins were expressed and screened in high-throughput experiments by Dr. Rappuoli’s vaccine research group (1). For the first time in 35 years, 7 novel protective and conserved vaccine candidates were identified. A subset of these candidates has been shown to provide immune protection in human clinical trials and the 4CMenB vaccine is now on the market. In another study, I performed comparative genomics of Mycobacterium abscessus subsp. massiliense isolates from outbreaks in cystic fibrosis centers in the USA and UK (see also "Analysis of pathogen diversity using whole genome sequencing"). Strains from the two cystic fibrosis outbreaks showed high-level relatedness with each other despite their geographical distance. We identified unique SNPs and genomic traits in outbreak strains and designed two PCR-based diagnostic strategies for use in the clinical setting (4). Our findings highlighted the necessity of identifying M. abscessusto the subspecies level and screening all cystic fibrosis isolates for relatedness to these outbreak strains.
    1. Pizza M, Scarlato V, Masignani V, Giuliani MM, Aricò B, et al. Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing. Science. 2000 Mar 10;287(5459):1816-20. PubMed PMID: 10710308.
    2. Maione D, Margarit I, Rinaudo CD, Masignani V, Mora M, et al. Identification of a universal Group B Streptococcus vaccine by multiple genome screen. Science. 2005 Jul 1;309(5731):148-50. PubMed PMID: 15994562; PubMed Central PMCID: PMC1351092.
    3. Moriel DG, Bertoldi I, Spagnuolo A, Marchi S, et al. Identification of protective and broadly conserved vaccine antigens from the genome of extraintestinal pathogenic Escherichia coli. Proc Natl Acad Sci U S A. 2010 May 18;107(20):9072-7. PubMed PMID: 20439758; PubMed Central PMCID: PMC2889118.
    4. Tettelin H, Davidson RM, Agrawal S, Aitken ML, Shallom S, et al. High-level relatedness among Mycobacterium abscessus subsp. massiliense strains from widely separated outbreaks. Emerg Infect Dis. 2014 Mar;20(3):364-71. PubMed PMID: 24565502; PubMed Central PMCID: PMC3944860.
  3. Large-scale bioinformatics. A significant fraction of my efforts are dedicated towards the development, optimization, and use of bioinformatics tools and pipelines. I led the most recent developments of the Sybil comparative genomics package (3). Sybil is an open source web-based software package for bacterial comparative genomics. It provides a rich set of web interfaces at varying levels of resolution from the whole genome scale down to single genes. The visualizations in Sybil include over 20 interactive interfaces for mining genome conservation and variation. Sybil relies on the construction of paralogous and orthologous protein families for the detection of syntenic regions, analysis of a species’ pan-genome. An example of a publicly accessible instance of the Sybil system dedicated to the analysis of 90 Cutibacterium (formerly Propionibacterium) acnes genomes is available here. I also developed the whole genome multiple alignment-based Mugsy-Annotator tool for identification of clusters of syntenic orthologs (2). Nucleotide alignments make the approach more robust in presence of annotation discrepancies and overcome challenges associated with identification of orthologs based on protein sequence similarity. Finally, I have applied large-scale comparative genomics to the study of bacterial diversity, virulence and evolution. Recent examples include the identification of restriction-modification systems that drive the separation of Neisseria meningitidisisolates into distinct clades (1) and the characterization of the parallel evolution of pathogenic and commensal streptococci (4).
    1. Budroni S, Siena E, Dunning Hotopp JC, et al. Neisseria meningitidis is structured in clades associated with restriction modification systems that modulate homologous recombination. Proc Natl Acad Sci U S A. 2011 Mar 15;108(11):4494-9. PubMed PMID: 21368196; PubMed Central PMCID: PMC3060241.
    2. Angiuoli SV, Dunning Hotopp JC, Salzberg SL, Tettelin H. Improving pan-genome annotation using whole genome multiple alignment. BMC Bioinformatics. 2011 Jun 30;12:272. PubMed PMID: 21718539; PubMed Central PMCID: PMC3142524.
    3. Riley DR, Angiuoli SV, Crabtree J, Dunning Hotopp JC, Tettelin H. Using Sybil for interactive comparative genomics of microbes on the web. Bioinformatics. 2012 Jan 15;28(2):160-6. PubMed PMID: 22121156; PubMed Central PMCID: PMC3259440.
    4. Kilian M, Riley DR, Jensen A, Brüggemann H, Tettelin H. Parallel evolution of Streptococcus pneumoniae and Streptococcus mitis to pathogenic and mutualistic lifestyles. MBio. 2014 Jul 22;5(4):e01490-14. PubMed PMID: 25053789; PubMed Central PMCID: PMC4120201.
  4. Bacterial virulence studies using genome-wide transcriptional profiling. I have extensive experience in studying the genome-wide transcriptional response of bacterial and human cells under various growth conditions, including host-pathogen interactions, using spotted microarrays (1-3) and more recently using Illumina-based RNA deep sequencing (RNA-Seq)(3,4). In particular, I have used a combination of adherence assays, mutagenesis, and functional genomics to identify novel factors involved in adherence the pathogen Streptococcus pneumoniae to human pharyngeal epithelial cells (3). By contrasting these processes in two pneumococcal strains we showed that adherence and invasion capacities vary markedly by strain. Deletion mutagenesis of five gene regions identified as regulated in this study revealed partial to complete attenuation in adherence. Viral upper respiratory tract infections are associated with increased colonization by S. pneumoniae but the mechanisms underlying this relationship are unclear. We profiled the genome-wide transcriptional response of human pharyngeal cells, with or without prior viral infection, in response to pneumococcal adherence. Adherence of S. pneumoniaeto human pharyngeal cells was significantly augmented in the presence of RSV or HPIV3 infection. These studies identified bacterial and host genes that can be used for vaccine development or as therapeutic targets to prevent pneumococcal adherence to epithelial cells, the first step of bacterial invasion of the host.
    1. Jiang SM, Ishmael N, Dunning Hotopp J, Puliti M, Tissi L, et al. Variation in the group B Streptococcus CsrRS regulon and effects on pathogenicity. J Bacteriol. 2008 Mar;190(6):1956-65. PubMed PMID: 18203834; PubMed Central PMCID: PMC2258897.
    2. Sanchez CJ, Kumar N, Lizcano A, Shivshankar P, et al. Streptococcus pneumoniae in biofilms are unable to cause invasive disease due to altered virulence determinant production. PLoS One. 2011;6(12):e28738. PubMed PMID: 22174882; PubMed Central PMCID: PMC3234282.
    3. Kimaro Mlacha SZ, Romero-Steiner S, Hotopp JC, et al. Phenotypic, genomic, and transcriptional characterization of Streptococcus pneumoniae interacting with human pharyngeal cells. BMC Genomics. 2013 Jun 9;14:383. PubMed PMID: 23758733; PubMed Central PMCID: PMC3708772.
    4. Chancey ST, Bai X, Kumar N, Drabek EF, Daugherty SC, et al. Transcriptional Attenuation Controls Macrolide Inducible Efflux and Resistance in Streptococcus pneumoniae and in Other Gram-Positive Bacteria Containing mef/mel(msr(D)) Elements. PLoS One. 2015;10(2):e0116254. PubMed PMID: 25695510; PubMed Central PMCID: PMC4335068.
  5. The bacterial species pan-genome concept. Next generation sequencing technologies have engendered a genome sequence data deluge in public databases. Genome analyses have transitioned from single or few genomes to hundreds to thousands of genomes. Pan-genome analyses are now widely applied, including for eukaryotic microbes, and provide a framework for estimating the genomic diversity of the dataset at hand and predicting the number of additional whole genomes sequences that would be necessary to fully characterize that diversity. I pioneered the concept of the bacterial species pan-genome while studying genomes of Streptococcus agalactiae (group B Streptococcus) (1). We determined that a pan-genome is composed of a conserved core genome surrounded by varying degrees of genomic diversity. We demonstrated that for many bacteria, including many human pathogens, this intra-species diversity results in a pan-genome much larger than any individual genome (1-4), and therefore no single genome is fully representative of the species, one of my motivations for modern reference-free comparative genomics.
    1. Tettelin H, Masignani V, Cieslewicz MJ, et al. Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: implications for the microbial "pan-genome". Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13950-5. PubMed PMID: 16172379; PubMed Central PMCID: PMC1216834.
    2. Tettelin H, Riley D, Cattuto C, Medini D. Comparative genomics: the bacterial pan-genome. Curr Opin Microbiol. 2008 Oct;11(5):472-7. PubMed PMID: 19086349.
    3. Donati C, Hiller NL, Tettelin H, Muzzi A, Croucher NJ, et al. Structure and dynamics of the pan-genome of Streptococcus pneumoniae and closely related species. Genome Biol. 2010;11(10):R107. PubMed PMID: 21034474; PubMed Central PMCID: PMC3218663.
    4. Vernikos G, Medini D, Riley DR, Tettelin H. Ten years of pan-genome analyses. Curr Opin Microbiol. 2015 Feb;23C:148-154. PubMed PMID: 25483351.

Awards and Affiliations

Affiliate, Federation of European Microbiological Societies (FEMS)

Member, American Society for Microbiology (ASM)

Grants and Contracts

2014/11/01-2017/10/31 – 1R01AI114800-01, University of Alabama at Birmingham, National Institute of Allergy and Infectious Diseases (NIAID) prime, Orihuela, Carlos (PI). “Cardiac microlesion formation during invasive pneumococcal disease.” Streptococcus pneumoniae, the leading cause of community-acquired pneumonia, can enter the heart’s myocardium during invasive pneumococcal disease and form microlesions. Our goal is to discern the host-pathogen interactions that occur during cardiac microlesion formation and identify targets for intervention. We are using RNA-Seq to compare the gene expression profile of S. pneumoniae in cardiac microlesions to those in the blood of infected mice. Role: Co-Investigator.

2015/09/01-2019/08/31 – 2U19AI084044-07, NIAID, Ravel, Jacques and Bavoil, Patrick (PIs). “Ecopathogenomics of sexually transmitted infections (EPSTI) – Core B, Genomics.” The focus of this application is on the discovery of biomarkers with applications in diagnosis, prevention and treatment of Chlamydia trachomatis and Neisseria gonorrhoeae mono- and co-infections. It comprises three projects that will evaluate the human genetics component of the infections, the host response (immune and miRNA) as well as the genital microbiome. Role: Core B lead.

2015/11/15-2018/08/31 – 5R01AI01964130, University of Buffalo, SUNY, NIAID prime, Murphy, Timothy (PI). “Persistent Haemophilus influenzae in COPD - Virulence, vaccines and antibiotic resistance.” In an 18-year ongoing prospective study on chronic obstructive pulmonary disease (COPD), Dr. Murphy established that a large proportion of patients show persistent colonization by non-typeable Haemophilus influenzae (NTHi). Genomic analysis of the strains and metadata allows us to: elucidate mechanisms by which NTHi persists in the COPD lung, assess the host effect on stability of putative vaccine antigen, and explore NTHi mechanisms of antimicrobial resistance and tolerance. Role: Co-investigator.

2015/12/16-2017/12/15 – 1R21AI117088-01A1, New York Medical College, NIAID prime, Bessen, Debra (PI). “Population analysis of group A streptococcal phenotypes.” We hypothesize that rheumatogenicity is, at least in part, a function of a group A Streptococcus (GAS) phenotype that is related to SpeB activity. SpeB is a key biomarker for the transcriptional program of the bacterial cell, as well as a virulence factor that acts by degrading human host proteins involved in defense. We aim to define the environmental growth conditions and molecular mechanisms that differentiate acute rheumatic fever- and pharyngitis-associated GAS for SpeB activity. Role: Co-investigator.

2016/06/24-2018/05/31 – 1R21AI125907-01, University of Washington, NIAID prime, Rajagopal, Lakshmi (PI). “Role of human cervical mucus plugs in ascending GBS infection.” Group B Streptococci (GBS) cause preterm births, stillbirths and early onset infections in newborns. Although GBS normally reside as commensal organisms in the lower genital tract of healthy women, the events that promote transmission of GBS to the amniotic cavity and fetus are unknown. The objective of this proposal is to define the role of the human cervical mucus plug in prevention of GBS growth and to determine if GBS sense cervical mucus plugs and modify virulence factor expression leading to ascending infection and fetal injury. Role: Co-investigator.

Links of Interest

Herve Tettelin, PhD

Academic Title:

Associate Professor

Primary Appointment:

Microbiology and Immunology