Dr. B. Linz

Research areas

Pathogenesis of Bordetella pertussis infection

Bordetella pertussis is the causative agent of Whooping Cough, a notifiable respiratory disease. Although the current acellular vaccines protect against the disease symptoms, there is growing evidence that B. pertussis continues to circulate in even highly vaccinated populations. The recent pertussis epidemics in many countries, including Germany, have shown how remarkably little we know and understand the pathophysiology during the initial colonization of the human upper airways by B. pertussis. This initial, catarrhal phase of B. pertussis infection, which is highly contagious, is characterized by massive mucus secretion, a heavily runny nose, sneezing and mild coughing, spreading copious amounts of bacteria. Detailed investigation of this catarrhal phase is necessary for the development of new therapeutics and improved pertussis vaccines that prevent transmission of the pathogen, but progress has been hampered by the lack of suitable experimental systems.

In my laboratory, we apply our novel and innovative experimental mouse models that enable us, for the first time, to study the catarrhal phase of B. pertussis infection in mechanistic detail. To identify the bacterial factors that elicit it we analyze the gene expression profile of B. pertussis during this phase. Using isogenic knock-out or loss-of-function mutants in comparison to the parental wild type bacteria, we assess the role of these factors during the initial colonization, during inflammation of the host mucosa, mucus production, bacterial shedding from the nose of infected mice, and during transmission between cage mates. We analyze the interaction of the bacterial factors with host cell receptors and the effect on the host immune response.

These studies are complemented by in vitro analyses at the air-liquid interface cell culture. In this system, bronchial cells differentiate into a pseudostratified epithelium that forms functional tight and adherens junctions as well as cilia. Following our hypothesis that these bacterial factors damage the functional integrity of the epithelium, we determine their effect on the epithelial layer by measuring the trans-epithelial electrical resistance, bacterial transmigration through the cell layer, and by examining the structural integrity of the cell layer by confocal microscopic using fluorescent antibodies against various cell junction proteins.

 

Publications

Publications Dr. B. Linz

Rivera I., Linz B., Harvill E.T. (2020).  Evolution and conservation of Bordetella intracellular survival in eukaryotic host cells. Front. Microbiol. 11: 557819. (equal first author)

 

Dewan K.K., Linz B., DeRocco S., Harvill E.T. (2020).  Acellular Pertussis Vaccine Components: Today and tomorrow. Vaccines 8: 217.

 

Rivera I., Linz B., Dewan K.K., Ma L., Rice C.A., Kyle D.E., Harvill E.T. (2019).  Conservation of ancient genetic pathways for intracellular persistence among animal pathogenic bordetellae.  Front. Microbiol. 10: 2839.

 

Gestal M.C., Howard L.K., Dewan K.K., Johnson H.M., Barbier M., Bryant C., Hamidou Soumana I., Rivera I., Linz B., Blas-Machado U., Harvill E.T. (2019).  Enhancement of immune response against Bordetella spp. by disrupting immunomodulation. Scientific Reports 9: 20261.

 

Maixner F., Thorell K., Granehäll L., Linz B., Moodley Y., Rattei T., Engstrand L., Zink A. (2019).  Helicobacter pylori in ancient human remains. World J Gastroenterol. 25: 6289-6298.

 

Linz B., Ma L., Rivera I., Harvill E.T. (2019).  Genotypic and phenotypic adaptation of pathogens: lesson from the genus Bordetella. Curr. Opin. Infect. Dis. 32: 223-230.

 

Skarlupka A.L., Linz B., Maynard J.A., Harvill E.T. (2019). Basics of pertussis pathogenesis. In: Rohani P. & Scarpiono S.V. (eds.) The integrative biology of Pertussis: epidemiology, immunology & evolution.  Oxford University Press, Oxford, UK, Chapter 2, pp. 26-41.

 

Linz B., Mukhtar N., Shabbir M.Z., Ivanov Y.V., Rivera I., Tahir Z., Yacub T., Harvill E.T. (2018).  Virulent epidemic pneumonia in sheep caused by the human pathogen Acinetobacter baumanniiFront. Microbiol. 9: 2616.

 

Gestal M.C., Rivera I., Howard L.K., Dewan K., Hamidou Soumana I., Dedloff M., Nicholson T.L., Linz B., Harvill E.T. (2018).  Blood or serum exposure induce global transcriptional changes, altered antigenic profile, and increased cytotoxicity by Classical Bordetellae.  Front. Microbiol. 9: 1969.

 

Taylor-Mulneix D.L., Hamidou Soumana I., Linz B., Harvill E.T. (2017).  Evolution of bordetellae from environmental microbes to human respiratory pathogens: amoebae as a missing link.  Front. Cell. Infect. Microbiol. 7: 510. (equal first author)

 

Junqueira A.C.M., Ratan A., Acerbi E., Drautz-Moses D.I., Premkrishnan B.N.V., Costea P.I., Linz B., Purbojati R.W., Paulo D.F., Gaultier N.E., Subramanian P., Hasan N.A., Colwell R.R., Bork P., Azeredo-Espin A.M.L., Bryant D.A., Schuster S.C. (2017).  The microbiomes of blowflies and houseflies as bacterial transmission reservoirs.  Scientific Reports 7: 16324.

 

Taylor-Mulneix D.L., Bendor L., Linz B., Rivera I., Ryman V.E., Dewan K.K., Wagner S.M., Wilson E.F., Hilburger L.J., Cuff L.E., West C.M., Harvill E.T. (2017).  Bordetella bronchiseptica exploits the complex lifecycle of Dictyostelium discoideum as an amplifying transmission vector.  PLoS Biology 15: e2000420.

 

Hamidou Soumana I., Linz B., Harvill E.T. (2017).  Environmental origin of the genus BordetellaFront. Microbiol. 8: 28. (equal first author)

 

Ivanov Y.V., Linz B., Register K.B., Newman J., Taylor D.L., Boschert K.R., LeGuyon S., Wilson E.F., Brinkac L.M., Sanka R., Greco S.C., Klender P.M., Losada L., Harvill E.T. (2016).  Identification and taxonomic classification of Bordetella pseudohinzii spp. nov. isolated from laboratory-raised mice.  Int. J. Syst. Evol. Microbiol. 66: 5452-5459. (equal first author)

 

Linz B., Ivanov Y.V., Preston A., Brinkac L.M., Parkhill J., Kim M., Harris S., Goodfield L.L., Gorringe A., Fry N., Nicholson T.L., Register K.B., Losada L., Harvill E.T. (2016).  Acquisition and loss of virulence-associated factors during genome evolution and speciation in three clades of Bordetella species.  BMC Genomics 17: 767.

 

Maixner F., Krause-Kyora B., Turaev D., Herbig A., Hoopmann M.R., Krusebauch U., Vigl E.E., Malfertheiner P., Megraud F., O´Sullivan N., Cipollini G., Coia V., Samadelli M., Engstrand L., Linz B., Moritz R.L., Grimm R., Krause J., Nebel A., Moodley Y., Rattei T., Zink A. (2016).  The 5300-year-old Helicobacter pylori genome of the Iceman. Science 351: 162-165.

 

Ivanov Y.V., Shariat N., Register K.B., Linz B., Rivera I., Hu K., Dudley E.G., Harvill E.T. (2015).  A newly discovered Bordetella species carries a transcriptionally active CRISPR-Cas with a small Cas9 endonuclease.  BMC Genomics 16: 863.

 

Bendor L., Weyrich L.S., Linz B., Rolin O.Y., Taylor D.L., Goodfield L.L., Smallridge W.E., Kennett M.J., Harvill E.T. (2015).  Type six secretion system of Bordetella bronchiseptica and adaptive immune components limit intracellular survival during infection. PLoS ONE 10: e0140743.

 

Montano V., Didelot X., Foll M., Linz B., Reinhardt R., Suerbaum S., Moodley Y., Jensen J.D. (2015).  Worldwide population structure, long term demography, and local adaptation of Helicobacter pyloriGenetics 200: 947-963.

 

Linz B., Windsor H.M., McGraw J.J., Hansen L.M., Gajewski J.P., Tomsho L.P., Hake C.M., Solnick J.V., Schuster S.C., Marshall B.J. (2014).  A mutation burst during the acute phase of Helicobacter pylori infection in humans and rhesus macaques. Nature Communications 5: 4165.

 

Linz B., Vololonantenainab C.R.R., Seck A., Carod J.F., Dia D., Garin B., Ramanampamonjy R.M., Thiberge J.M., Raymond J., Breurec S. (2014).  Population genetic structure and isolation by distance of Helicobacter pylori in Senegal and Madagascar. PLoS ONE 9: e87355.

 

Linz B., Windsor H.M, Gajewski J.P., Hake C.M., Drautz D.I., Schuster S.C., Marshall B.J. (2013).  Helicobacter pylori genomic microevolution during naturally occurring transmission between adults.  PLoS ONE 8: e82187.

 

Nell S., Eibach D., Montano V., Maady A., Nkwescheu A., Siri J., Elamin W.F., Falush D., Linz B., Achtman M., Moodley Y., Suerbaum S. (2013).  Recent Acquisition of Helicobacter pylori by Baka Pygmies.  PLoS Genet. 9: e1003775.

 

Maldonado-Contreras A., Mane S.P., Zhang X.S., Pericchi L., Alarcon T., Contreras M., Linz B., Blaser M.J., Dominguez-Bello M.G. (2013).  Phylogeographic evidence of cognate recognition site patterns and transformation efficiency differences in H. pylori: theory of strain dominance.  BMC Microbiol. 13: 211.

 

Moodley Y., Linz B., Bond R.P., Nieuwoudt M., Soodyal H., Schlebusch C., Bernhöft S., Hale J., Suerbaum S., Mugisha L., van der Merwe S.W., Achtman M. (2012).  Age of the association between Helicobacter pylori and man. PLoS Pathogens 8: e1002693. (equal first author)

 

Breurec S., Guillard B., Hem S., Papadakos K.S., Brisse S., Huerre M., Monchy D., Oung C., Sgouras D.N., Tan T.S., Thiberge J.M., Vong S., Raymond J., Linz B. (2011).  Expansion of European vacA and cagA alleles to East-Asian Helicobacter pylori strains in Cambodia. Infect. Genet. Evol. 11: 1899-1905.

 

Breurec S., Guillard B., Hem S., Brisse S., Dieye F.B., Huerre M., Oung C., Raymond J., Tan T.S., Thiberge J.M., Vong S., Monchy D., Linz B. (2011).  Evolutionary history of Helicobacter pylori sequences reflect past human migrations in Southeast Asia. PLoS ONE 6: e22058.

 

Olbermann P., Josenhans C., Moodley Y., Uhr M., Stamer C., Vauterin M., Suerbaum S., Achtman M., Linz B. (2010).  A global overview of the genetic and functional diversity in the Helicobacter pylori cag pathogenicity island. PLoS Genet. 6: e1001069.

 

Latifi-Navid S., Ghorashi S.A., Siavoshi F., Linz B., Massarrat S., Khegay T., Salmanian A.H., Shayesteh A.A., Masoodi M., Ghanadi K., Ganji A., Suerbaum S., Achtman M., Malekzadeh R., Falush D. (2010).  Ethnic and geographic differentiation of Helicobacter pylori within Iran.  PLoS ONE 5: e9645.

 

Jores J., Meens J., Buettner F.F.R., Linz B., Naessens J., Gerlach G.F. (2009).  Analysis of the immunoproteome of Mycoplasma mycoides subsp. mycoides small colony type reveals immunogenic homologues to other known virulence traits in related Mycoplasma species. Vet. Immunol. Immunopathol. 131: 238-245.

 

Moodley Y., Linz B. (2009).  Helicobacter pylori sequences reflect past human migrations.  In: de Reuse H., Bereswill S. (eds): Microbial Pathogenomics. Genome Dyn. Basel, Karger, 2009, vol 6, pp 62–74.

 

Moodley Y., Linz B., Yamaoka Y., Windsor H.M., Breurec S., Wu J.-Y., Maady A., Bernhöft S., Thiberge J.-M., Phuanukoonnon S., Jobb G., Siba P., Graham D.Y., Marshall B.J., Achtman M. (2009).  The peopling of the Pacific from a bacterial perspective. Science 323: 527-530. (equal first author)

 

Schuster S.C., Wittekindt N.E., Linz B. (2008).  Molecular mechanisms of host adaptation in Helicobacter. In: Yamaoka, Y. (ed.) Helicobacter pylori: Molecular Genetics and Cellular Biology. Horizon Scientific Press, Wymondham, UK, Chapter 10, pp. 193-204.

 

Dominguez-Bello M.G., Pérez M.E., Bortolini M.C., Salzano F.M., Pericci L.R., Zambrano-Guzman O., Linz B. (2008).  Amerindian Helicobacter pylori strains go extinct, as European strains expand their host range.  PLoS ONE 3: e3307.

 

Linz B., Schuster S.C. (2007).  Genomic diversity in Helicobacter and related organisms. Res. Microbiol. 158: 737-744.

 

Josenhans C., Beier D., Linz B., Meyer T.F., Suerbaum S. (2007).  Pathogenomics of Helicobacter. Int. J. Med. Microbiol. 297: 589-600.

 

Linz B., Balloux F., Moodley Y., Manica A., Liu H., Roumagnac P., Falush D., Stamer C., Prugnolle F., van der Merwe S.W., Yamaoka Y., Graham D.Y., Perez-Trallero E., Wadstrom T., Suerbaum S., Achtman M. (2007).  An African origin for the intimate association between humans and Helicobacter pyloriNature 445: 915-918.

 

Andrzejewska J., Lee S.K., Olbermann P., Lotzing N., Katzowitsch E., Linz B., Achtman M., Kado C.I., Suerbaum S, Josenhans C. (2006).  Characterization of the pilin ortholog of the Helicobacter pylori type IV cag pathogenicity apparatus, a surface-associated protein expressed during infection.  J. Bacteriol. 188: 5865-5877.

 

Eppinger M., Baar C., Linz B., Raddatz G., Lanz C., Keller H., Morelli G., Gressmann H., Achtman M., Schuster S.C. (2006).  Who ate whom? Adaptive Helicobacter genomic changes that accompanied a host jump from primates to large felines. PLoS Genet. 2: e120.

 

Momynaliev K.T., Chelysheva V.V., Acopian T.A., Selezneva O.V., Linz B., Achtman M., Govorun V.M. (2005).  Population identification of Helicobacter pylori isolates from Russia. Genetika 41: 1182-1185. (in russian)

 

Gressmann H., Linz B., Ghai R., Pleissner K.-P., Schlapbach R., Yamaoka Y., Kraft C., Suerbaum S., Meyer T.F., Achtman M. (2005).  Gain and loss of multiple genes during the evolution of Helicobacter pyloriPLoS Genet. 1: e43.

 

Wirth T., Wang X., Linz B., Novick R.P., Lum K., Blaser M., Morelli G., Falush D., Achtman M. (2004).  Distinguishing human ethnic groups via sequences from Helicobacter pylori: lessons from Ladakh. Proc. Natl. Acad. Sci. USA 101: 4746-4751.

 

Salaun L., Linz B., Suerbaum S., Saunders N. (2004).  The diversity within an expanded and re-defined repertoire of phase variable genes in Helicobacter pylori. Microbiology 150: 817-830.

 

Falush D., Wirth T., Linz B., Pritchard J.K., Stephens M., Kidd M., Blaser M.J., Graham D.Y., Vacher S., Perez-Perez G.I., Yamaoka Y., Mégraud F., Otto K., Reichard U., Katzowitsch E., Wang X., Achtman M., Suerbaum S. (2003).  Traces of human migrations in Helicobacter pylori populations.  Science 299: 1582-1585.

 

Kidgell C., Reichard U., Wain J., Linz B., Torpdahl M., Dougan G., Achtman M. (2002). Salmonella typhi, the causative agent of typhoid fever, is approximately 50,000 years old. Infect. Genet. Evol. 2: 39-45.

 

Zhu P., van der Ende A., Falush D., Brieske N., Morelli G., Linz B., Popovic T., Schuurman I.G.A., Adegbola R.A., Zurth K., Gagneux S., Platonov A.E., Riou J.-Y., Caugant D.A., Nicolas P., Achtman M. (2001).  Fit genotypes and escape variants of subgroup III Neisseria meningitidis during three pandemics of epidemic meningitis. Proc. Natl. Acad. Sci. USA 98: 5234-5239.

 

Linz B., Schenker M., Zhu P., Achtman M. (2000).  Frequent interspecific genetic exchange between commensal neisseriae and Neisseria meningitidis. Mol. Microbiol. 36: 1049-1058.

 

Linz B., Schenker M., Achtman M. (1999).  A global genpool in the neisseriae. Biospektrum 2.99: 111-112. (in german)

 

Linz B., Linz A., Migunova A.V., Kvitko K.V. (1999).  Correlation between virus-sensitivity and isoenzyme spectrum in symbiotic Chlorella-like algae. Protistology 1: 76-81.

 

Vilela C., Ramirez C.V., Linz B., Rodrigues-Pousada C., McCarthy J.E.G. (1999). Post-termination ribosome interactions with the 5’UTR modulate yeast mRNA stability. EMBO J. 18: 3139-3152.

 

Till D.D., Linz B., Seago J.E., Elgar S.J., Marujo P.E., Elias M.D., Arraiano C.M., McClellan J.A., McCarthy J.E.G., Newbury S.F. (1998) Identification and developmental expression of a 5′-3′ exoribonuclease from Drosophila melanogaster. Mech. Dev. 79: 51-55.

 

Vilela C., Linz B., Rodrigues-Pousada C., McCarthy J.E.G. (1998).  The yeast transcription factor genes YAP1 and YAP2 are subject to differential control at the levels of both translation and mRNA stability. Nucleic Acids Res. 26: 1150-1159.

 

Linz B., Koloteva N., Vasilescu S., McCarthy J.E.G. (1997).  Disruption of ribosomal scanning on the 5′-untranslated region, and not restriction of translational initiation per se, modulates the stability of nonaberrant mRNAs in the yeast Saccharomyces cerevisiae. J. Biol. Chem. 272: 9131-9140.

 

Vasilescu S., Ptushkina M., Linz B., Müller P.P., McCarthy J.E.G. (1996).  Mutants of eukaryotic initiation factor eIF-4E with altered mRNA cap binding specificity reprogram mRNA selection by ribosomes in Saccharomyces cerevisiae. J. Biol. Chem. 271: 7030-7037.

 

Kvitko K.V., Voicechovskij E.V., Migunova A.V., Pioch D., Linz B. (1994).  Symbiotic index as a valuation of the conditions in water ecosystems: an example of polygon „Krasny Bor“ basins and its sanitary zone. Problems of ecology and natural preservation 4: 47-57. (in russian).

 

Voicechovskij E.V., Linz B., Kvitko K.V., Gavrilova O.V. (1994).  The finding of an American ecotype zoochlorella virus in Tadjikistan. Vestnik Leningrad University 3 (N3):105-106. (in russian).

 

 

 

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