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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:

Health Sciences Facility III, 670 West Baltimore St, Baltimore 21201

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).

Hervé Tettelin

Biosketch

I have been in the genomics field for over 25 years, developing 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

Zella D., Curreli S., Benedetti F., Krishnan S., Cocchi F., Latinovic O.S., Denaro F., Romerio F., Djavani M., Charurat M.E., Bryant J.L., Tettelin H., and Gallo R.C. (2018) Mycoplasma promotes malignant transformation in vivo, and its DnaK, a bacterial chaperone protein, has broad oncogenic properties. Proc. Natl Acad. Sci. USA 115, E12005-E12014. Press release.

Murphy T.F., Brauer A.L., Pettigrew M.M., LaFontaine E.R., and Tettelin H. (2018) Persistence of Moraxella catarrhalis in chronic obstructive pulmonary disease and regulation of the Hag/MID adhesin. J. Infect. Dis. 219, 1448-1455.

Pettigrew M.M., Ahearn C.P., Gent J.F., Kong Y., Gallo M.C., Munro J.B., D’Mello A., Sethi S., Tettelin H.*, and Murphy, T.F.* (2018Haemophilus influenzae genome evolution during persistence in the human airways in chronic obstructive pulmonary disease.  Proc. Natl. Acad. Sci. USA 115, E3256-E3265. [*These authors contributed equally to this work] Press release.

Shenoy A.T., Brissac T., Gilley R.P., Kumar N., Wang Y., Brissac T., Gonzalez-Juarbe N., Hinkle W.S., Daugherty S.C., Shetty A.C., Ott S., Tallon L.J., Deshane J., Tettelin H., and Orihuela C.J. (2017Streptococcus pneumoniae in the heart subvert the host response through biofilm-mediated resident macrophage killing. PLoS Pathog. 13, e1006582.

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.

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.

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

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.

Additional Publication Citations

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

 

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.

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.

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.

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.

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.

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.

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

 

Campo J.J., Le T.Q., Pablo J.V., Hung C., Teng A.A., Tettelin H., Tate A., Hanage W.P., Alderson M.R., Liang X., Malley R., Lipsitch M., Croucher N.J. (2018Panproteome-wide analysis of antibody responses to whole cell pneumococcal vaccination. eLife 28, e37015.

Zella D., Curreli S., Benedetti F., Krishnan S., Cocchi F., Latinovic O.S., Denaro F., Romerio F., Djavani M., Charurat M.E., Bryant J.L., Tettelin H., and Gallo R.C. (2018Mycoplasma promotes malignant transformation in vivo, and its DnaK, a bacterial chaperone protein, has broad oncogenic properties. Proc. Natl Acad. Sci. USA 115, E12005-E12014. Press release.

Murphy T.F., Brauer A.L., Pettigrew M.M., LaFontaine E.R., and Tettelin H. (2018Persistence of Moraxella catarrhalis in chronic obstructive pulmonary disease and regulation of the Hag/MID adhesin. J. Infect. Dis. 219, 1448-1455.

Chung M., Munro J.B., Tettelin H., and Dunning Hotopp J.C. (2018) Using core genome alignments to assign bacterial species. mSystems 3(6), e00236-18.

Pettigrew M.M., Ahearn C.P., Gent J.F., Kong Y., Gallo M.C., Munro J.B., D’Mello A., Sethi S., Tettelin H.*, and Murphy, T.F.* (2018Haemophilus influenzae genome evolution during persistence in the human airways in chronic obstructive pulmonary disease.  Proc. Natl. Acad. Sci. USA 115, E3256-E3265. [*These authors contributed equally to this work] Press release.

Hooven T.A., Catomeris A.J., Bonakdar M., Tallon L.J., Santana-Cruz I., Ott S., Daugherty S.C., Tettelin H., and Ratner A.J. (2018) The Streptococcus agalactiae stringent response enhances virulence and persistence in human blood.  Infect. Immun. 86, e00612-17.

Tettelin H., Hooven T.A., Zhao X., Su Q., Sadzewicz L., Tallon L.J., Fraser C.M., and Ratner A.J. (2017) Whole genome sequences of bacteremia isolates of Bordetella holmesii.  Genome Announc. 5, pii: e01023-17.

Salerno-Gonçalves R.*, Tettelin H.*, Lou D., Steiner S., Rezwanul T., Guo Q., Picking W.D., Nene V., and Sztein M.B. (2017) Use of a novel antigen expressing system to study the Salmonella enterica serovar Typhi protein recognition by T cells. PLoS Negl. Trop. Dis. 11, e0005912. [*These authors contributed equally to this work]

Shenoy A.T., Brissac T., Gilley R.P., Kumar N., Wang Y., Brissac T., Gonzalez-Juarbe N., Hinkle W.S., Daugherty S.C., Shetty A.C., Ott S., Tallon L.J., Deshane J., Tettelin H., and Orihuela C.J. (2017) Streptococcus pneumoniae in the heart subvert the host response through biofilm-mediated resident macrophage killing. PLoS Pathog. 13, e1006582.

Le Breton Y., Belew A.T., Freiberg J.A., Sundar G.S., Islam E., Lieberman J., Shirtliff M.E., Tettelin H., El-Sayed N.M., and McIver K.S. (2017) Genome-wide discovery of novel M1T1 group A streptococcal determinants important for fitness and virulence during soft-tissue infection. PLoS Pathog. 13, e1006584.

Chen F., Szymanski E.P., Olivier K.N., Liu X., Tettelin H., Holland S.M., Duggal P. (2017) Whole exome sequencing identifies the 6q12-q16 linkage region and a candidate gene TTK for pulmonary nontuberculous mycobacterial disease. Am. J. Respir. Crit. Care Med. 196, 1599-1604.

Agrawal S., Arze C., Adkins R.S., Crabtree J., Riley D.R., Vangala M., Galens K., Fraser C.M., Tettelin H., White O., Angiuoli S.V., Mahurkar A., Fricke W.F. (2017) CloVR-Comparative: automated, cloud-enabled comparative microbial genome sequence analysis pipeline. BMC Genomics 18, 332.

Lomholt H.B., Scholz C.F.P., Brüggemann H., Tettelin H., and Kilian M. (2017) A comparative study of Cutibacterium (Propionibacterium) acnes clones from acne patients and healthy controls. Anaerobe 47, 57-63.

Panda A., Nagaraj S., Zhao X., Tettelin H., and DeTolla L.J. (2017) Complete genome sequences of Mycobacterium kansasii strains isolated from rhesus macaques. Genome Announc. 5, pii: e00187-17.

Lizcano A., Suresh Babu R.A., Shenoy A.T., Saville A.M., Kumar N., D’Mello A., Hinojosa C.A., Gilley R.P., Segovia J., Mitchell T.J., Tettelin H., and Orihuela C.J. (2017) Transcriptional organization of pneumococcal psrP-secY2A2 and impact of GtfA and GtfB deletion on PsrP-associated virulence properties. Microbes Infect. 19, 323-333.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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. 

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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).

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.

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

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.

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.

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.

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) (1997The 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. (1997An 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. (1996Life with 6000 genes. Science 274, 546-567.

Dujon B., ..., Tettelin H., ..., and Mewes H.W. (108 authors) (1994Complete 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. 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 whole genome sequences of Neisseria meningitidis (a), Streptococcus pneumoniae (b) and Streptococcus agalactiae (c). Over time, I have made use of the rapidly evolving genome sequencing technologies, from Sanger sequencing to 454, Illumina and Pacific Biosciences. Recently, I have conducted in-depth comparative genomics analyses of isolates of nontypeable Haemophilus influenzae (NTHi) that are critical to the pathogenesis of chronic obstructive pulmonary disease (COPD). We conducted whole-genome sequencing of 269 longitudinally collected cleared and persistent NTHi from a 15-y prospective study of adults with COPD (d). We elucidated the phylogeny of NTHi isolates, identified genomic changes that occur with persistence in the human airways, and evaluated the effect of selective pressure on candidate vaccine antigens. Slipped-strand mispairing, mediated by changes in simple sequence repeats in multiple genes during persistence, was found to regulate expression of critical virulence functions and to be a major mechanism for survival in the hostile environment of the human airways. Our results advanced our understanding of how a bacterial pathogen that plays a critical role in COPD adapts to survival in the human respiratory tract.

a.     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.

b.     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.

c.     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; PMCID: PMC129455.

d.     Pettigrew M.M., Ahearn C.P., Gent J.F., Kong Y., Gallo M.C., Munro J.B., D’Mello A., Sethi S., Tettelin H.*, and Murphy, T.F.* [*These authors contributed equally to this work] Haemophilus influenzae genome evolution during persistence in the human airways in chronic obstructive pulmonary disease. Proc. Natl. Acad. Sci. U S A 2018 115(14): E3256-E3265. PubMed PMID: 29555745. PMCID: PMC5889651 (available October 3, 2018).

 

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 (a-c). 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 N. meningitidis 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 (a). 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. 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 (d). Our findings highlighted the necessity of identifying M. abscessus to the subspecies level and screening all cystic fibrosis isolates for relatedness to these outbreak strains. Finally, in a study focusing on human mycoplasmas that promote lymphomagenesis that was published last year, I identified a clade of DnaK bacterial sequences that are associated with cancer-causing bacteria, potentially opening new avenues towards new anti-cancer therapeutics.

a.     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.

b.     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; PMCID: PMC1351092.

c.     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; PMCID: PMC3944860.

d.     Zella D, Curreli S, Benedetti F, Krishnan S, Cocchi F, et al., Tettelin H, and Gallo RC. Mycoplasma promotes malignant transformation in vivo, and its DnaK, a bacterial chaperone protein, has broad oncogenic properties. Proc. Natl Acad. Sci. USA 2018 Dec 18;115(51):E12005-E12014. PubMed PMID: 30509983; PMCID: PMC6304983.

 

3.     Large-scale bioinformatics. A significant fraction of my effort is dedicated towards the development, optimization, and use of bioinformatics tools and pipelines. I led the most recent developments of the Sybil comparative genomics package (c). 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 at http://sybil-clovr.igs.umaryland.edu/sybil/ChristianScholz_Pacnes_sybil. I also developed the whole genome multiple alignment-based Mugsy-Annotator tool for identification of clusters of syntenic orthologs (b). 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 meningitidis isolates into distinct clades (a) and the characterization of the parallel evolution of pathogenic and commensal streptococci (d).

a.     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; PMCID: PMC3060241.

b.     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; PMCID: PMC3142524.

c.     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; PMCID: PMC3259440.

d.     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; 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 (a,b) and more recently using Illumina-based RNA deep sequencing (RNA-seq)(b-d). In particular, in collaboration with Dr. Carlos Orihuela at the University of Alabama at Birmingham, I have performed dual RNA-seq profiling of the host-pathogen interplay during disseminated Streptococcus pneumoniae infection in a mouse model. We were able to simultaneously profile bacterial and mouse gene responses using whole infected hearts, as well as infected blood. These studies led to the identification of novel anatomical site-specific expression of determinants of pneumococcal pathogenesis, gave insights into their mechanism of interaction with the host, and provided key information on currently considered and future protein candidates for vaccine development (d).

a.     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; PMCID: PMC3234282.

b.     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; PMCID: PMC3708772.

c.     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; PMCID: PMC4335068.

d.     Shenoy AT, Brissac T, Gilley RP, Kumar N, Wang Y, Brissac T, Gonzalez-Juarbe N, Hinkle WS, Daugherty SC, Shetty AC, Ott S, Tallon LJ, Deshane J, Tettelin H, and Orihuela CJ. Streptococcus pneumoniae in the heart subvert the host response through biofilm-mediated resident macrophage killing. PLoS Pathog. 2017 Aug 25;13(8):e1006582. PMID: 28841717. PMCID: PMC5589263.

 

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) (a). 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 (a-d), and therefore no single genome is fully representative of the species, one of my motivations for modern reference-free comparative genomics. I am currently editing the first book on the pan-genome that will be published by Springer.

a.     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; PMCID: PMC1216834.

b.     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.

c.     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; PMCID: PMC3218663.

d.     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

U19 AI084044                                                       Ravel/Bavoil (PIs)           09/01/15-08/31/19

Ecopathogenomics of sexually transmitted infections (EPSTI) – Core B, Genomics

The focus of this application is 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

R21 AI125907                                                       Rajagopal (PI)                 06/24/16-05/31/19 (NCE)

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

R21 DE027201                                                     Vickerman (PI)                07/01/17-06/30/19

Fitness profiling of Streptococcus gordonii in oral microenvironments

Streptococcus gordonii is an initial colonizer of the biofilm that forms tooth surfaces. Identification of S. gordonii genes essential for species survival and proliferation under synergistic or antagonistic conditions will provide essential insights into community dynamics that favor or disfavor a state of oral health. We will use Tn-seq to identify and examine genes involved in S. gordonii fitness under selected in vitro model conditions relevant to those in the oral cavity.

Role: Co-Investigator

CCT #2018-8914, Merck, Sharp and Dohme      Tettelin (PI)                      11/01/17-10/31/19

Dual RNA-seq for characterization of the Streptococcus pneumoniae and host transcriptomes during bacteremia/invasive disease

This proposal seeks to determine the molecular basis for S. pneumoniae survival at three anatomical sites: nasopharynx, lungs and blood. It does so by using powerful RNA-seq technology to identify the pneumococcal determinants expressed in an anatomical site-specific manner. The outlined experiments will advance our understanding of pneumococcal pathogenesis and inform our collective approach to the next generation of pneumococcal vaccines. Given that community-acquired pneumonia and the pneumococcus are a major cause of global morbidity and mortality, this is a highly worthwhile endeavor.

Role: PI

R21 AI130646                                                       Tettelin (PI)                      12/07/17-11/30/19

Omics-based identification of novel vaccine targets against Neisseria gonorrhoeae

Neisseria gonorrhoeae (GC) is the causative agent of the sexually transmitted infection (STI) gonorrhea. The ability of major surface proteins to vary their expression significantly complicates the development of a vaccine against GC. Our project focuses on GC changes that occur under relevant physiological conditions that would be encountered in vivo. We will apply RNA-seq and proteomics approaches to the study of 3D in vitro models of GC interacting with epithelial cells.

Role: PI

U01 CA221244                                                     Ruhl (PI)                          01/01/18-06/30/20

Harnessing the oral microbiome to provide novel glycan-binding probes

In the oral environment, interactions between lectin-like adhesins on bacteria and complementary glycan motifs on mucosal epithelia and saliva-coated tooth surfaces play central roles in initial bacterial colonization. The overall objective of this project is to expand and greatly diversify the tool box of available adhesins by harvesting novel ones from the oral microbiomes of other mammals that express strikingly different glycans. To this end we will sequence and mine genomes of diverse individual species from the oral microbiomes.

Role: Co-Investigator

R01 DE019807                                                     Ruhl (PI)                          07/01/18-06/30/23

Microbial recognition of sialic acid diversity in the oral cavity

Sialic acids are involved in cell-cell recognition processes and modulate a wide variety of physiological and pathological processes, including recognition by viruses and other pathogenic microorganisms. We aim to identify the natural receptors for specific streptococcal sialic acid in the human oral cavity. We will identify other bacterial species in oral biofilms that express sialic acids on their surface and are targets for inter-bacterial adhesion. The knowledge gained will impact early diagnosis and prevention of dental, oral and also systemic diseases caused by oral microbes.

Role: Co-Investigator

U19 AI110820                                                       Rasko/Fraser/White (PIs)   04/01/19-03/31/24

A genomics-based investigation of the determinants of polymicrobial infectious disease outcomes – Project 2

This project is composed of an assembly of studies that explore the dynamic interactions between pathogens, hosts, their microbiota and the immune system with the goal to provide a more comprehensive understanding of the determinants of infectious disease outcomes.

Role: Co-Investigator

Links of Interest