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研究领域

SYNOPSIS OF AREA OF INTEREST: Molecular determinants of pathogenesis and biofilm development; Regulation of gene expression; Host pathogen interactions, Vaccine development, Innate and adaptive immunity. 1. Functional Genomics. We have identified and published on several new genes and loci in Bordetella. We are currently utilizing in vitro systems, cell culture and mouse models (including knockout and immuno-deficient mice) to study their role in controlling gene expression, cellular adhesion, resistance to host defenses and respiratory tract colonization. 2. Development of effective vaccines. Alum, the current adjuvant in acellular pertussis vaccines fails to elicit appropriate immune responses for optimum protection against Bordetella pertussis, the human pathogen. Thus, substitution of alum with an adjuvant that induces Th1-type responses may increase vaccine efficacy. We have identified Bordetella Colonization Factor A (BcfA) as such an immune-stimulatory factor. BcfA has adjuvant function and induces Th1 type T cell responses. We are currently testing the ability of BcfA to enhance immune responses to current pertussis vaccines. We are also developing veterinary vaccines for Bordetella bronchiseptica, the causative agent of kennel cough in dogs and respiratory diseases in other animals. Our long term goal is to examine the utility of BcfA to generate effective immunity against other bacterial and viral pathogens. 3. Bacterial biofilms. Biofilms are highly structured communities of cells that are encased in a self-produced polymeric organic matrix and are increasingly recognized as important contributors to chronic or persistent diseases. We hypothesize that the prevalent nasopharyngeal carriage of Bordetella pertussis in adults and adolescents represents the biofilm state. The preliminary and published results with B. pertussis biofilms in mice strongly implicate this lifestyle in humans. We are examining the role of Bordetella factors in biofilm development in vitro and in animals. We are also investigating the contribution of the host innate and adaptive immunity in the progression and development of biofilms.

近期论文

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Chemical Synthesis and Immunological Evaluation of a Pentasaccharide Bearing Multiple Rare Sugars as a Potential Anti-pertussis Vaccine.Wang P, Huo CX, Lang S, Caution K, Nick ST, Dubey P, Deora R, Huang X.Angew Chem Int Ed Engl. 2020 Jan 17. doi: 10.1002/anie.201915913. Structural mechanism for regulation of DNA binding of BpsR, a Bordetella regulator of biofilm formation, by 6-hydroxynicotinic acid.Booth WT, Davis RR, Deora R, Hollis T.PLoS One. 2019 Nov 7;14(11):e0223387. doi: 10.1371/journal.pone.0223387. eCollection 2019. A porcine xenograft-derived bone scaffold is a biocompatible bone graft substitute: An assessment of cytocompatibility and the alpha-Gal epitope.Bracey DN, Seyler TM, Jinnah AH, Smith TL, Ornelles DA, Deora R, Parks GD, Van Dyke ME, Whitlock PW.Xenotransplantation. 2019 Sep;26(5):e12534. doi: 10.1111/xen.12534. Epub 2019 Jul 25. Bordetella Colonization Factor A (BcfA) Elicits Protective Immunity against Bordetella bronchiseptica in the Absence of an Additional Adjuvant.Yount KS, Jennings-Gee J, Caution K, Fullen AR, Corps KN, Quataert S, Deora R, Dubey P.Infect Immun. 2019 Sep 19;87(10). pii: e00506-19. doi: 10.1128/IAI.00506-19. Print 2019 Oct. Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice.Caution K, Yount K, Deora R, Dubey P.J Vis Exp. 2019 Feb 22;(144). doi: 10.3791/58930. Structural Analysis of Bordetella pertussis Biofilms by Confocal Laser Scanning Microscopy Cattelan N, Yantorno OM, Deora R.Bio Protoc. 2018 Aug 5;8(15). pii: e2953. doi: 10.21769/BioProtoc.2953. No abstract available. PgaB orthologues contain a glycoside hydrolase domain that cleaves deacetylated poly-β(1,6)-N-acetylglucosamine and can disrupt bacterial biofilms.Little DJ, Pfoh R, Le Mauff F, Bamford NC, Notte C, Baker P, Guragain M, Robinson H, Pier GB, Nitz M, Deora R, Sheppard DC, Howell PL.PLoS Pathog. 2018 Apr 23;14(4):e1006998. doi: 10.1371/journal.ppat.1006998. eCollection 2018 Apr. The Transcriptional Regulator BpsR Controls the Growth of Bordetella bronchiseptica by Repressing Genes Involved in Nicotinic Acid Degradation.Guragain M, Jennings-Gee J, Cattelan N, Finger M, Conover MS, Hollis T, Deora R.J Bacteriol. 2018 May 24;200(12). pii: e00712-17. doi: 10.1128/JB.00712-17. Print 2018 Jun 15. The Adjuvant Bordetella Colonization Factor A Attenuates Alum-Induced Th2 Responses and Enhances Bordetella pertussis Clearance from Mouse Lungs.Jennings-Gee J, Quataert S, Ganguly T, D'Agostino R Jr, Deora R, Dubey P.Infect Immun. 2018 May 22;86(6). pii: e00935-17. doi: 10.1128/IAI.00935-17. Print 2018 Jun. Bordetella Pertussis virulence factors in the continuing evolution of whooping cough vaccines for improved performance.Dorji D, Mooi F, Yantorno O, Deora R, Graham RM, Mukkur TK.Med Microbiol Immunol. 2018 Feb;207(1):3-26. doi: 10.1007/s00430-017-0524-z. Epub 2017 Nov 21. Review. Hyperbiofilm Formation by Bordetella pertussis Strains Correlates with Enhanced Virulence Traits.Cattelan N, Jennings-Gee J, Dubey P, Yantorno OM, Deora R.Infect Immun. 2017 Nov 17;85(12). pii: e00373-17. doi: 10.1128/IAI.00373-17. Print 2017 Dec. The Bordetella Bps Polysaccharide Is Required for Biofilm Formation and Enhances Survival in the Lower Respiratory Tract of Swine.Nicholson TL, Brockmeier SL, Sukumar N, Paharik AE, Lister JL, Horswill AR, Kehrli ME Jr, Loving CL, Shore SM, Deora R.Infect Immun. 2017 Jul 19;85(8). pii: e00261-17. doi: 10.1128/IAI.00261-17. Print 2017 Aug. Erratum for Carbonetti et al., "Highlights of the 11th International Bordetella Symposium: from Basic Biology to Vaccine Development".Carbonetti NH, Wirsing von König CH, Lan R, Jacob-Dubuisson F, Cotter PA, Deora R, Merkel TJ, van Els CA, Locht C, Hozbor D, Rodriguez ME.Clin Vaccine Immunol. 2017 May 5;24(5). pii: e00071-17. doi: 10.1128/CVI.00071-17. Print 2017 May. No abstract available. Highlights of the 11th International Bordetella Symposium: from Basic Biology to Vaccine Development.Carbonetti NH, Wirsing von König CH, Lan R, Jacob-Dubuisson F, Cotter PA, Deora R, Merkel TJ, van Els CA, Locht C, Hozbor D, Rodriguez ME.Clin Vaccine Immunol. 2016 Nov 4;23(11):842-850. Print 2016 Nov. Erratum in: Clin Vaccine Immunol. 2017 May 5;24(5):. Bordetella biofilms: a lifestyle leading to persistent infections.Cattelan N, Dubey P, Arnal L, Yantorno OM, Deora R.Pathog Dis. 2016 Feb;74(1):ftv108. doi: 10.1093/femspd/ftv108. Epub 2015 Nov 19. Review. The protein BpsB is a poly-β-1,6-N-acetyl-D-glucosamine deacetylase required for biofilm formation in Bordetella bronchiseptica.Little DJ, Milek S, Bamford NC, Ganguly T, DiFrancesco BR, Nitz M, Deora R, Howell PL.J Biol Chem. 2015 Sep 11;290(37):22827-40. doi: 10.1074/jbc.M115.672469. Epub 2015 Jul 22. Comparative analyses of a cystic fibrosis isolate of Bordetella bronchiseptica reveal differences in important pathogenic phenotypes.Sukumar N, Nicholson TL, Conover MS, Ganguly T, Deora R.Infect Immun. 2014 Apr;82(4):1627-37. doi: 10.1128/IAI.01453-13. Epub 2014 Jan 27. The Bordetella pertussis Bps polysaccharide enhances lung colonization by conferring protection from complement-mediated killing.Ganguly T, Johnson JB, Kock ND, Parks GD, Deora R.Cell Microbiol. 2014 Jul;16(7):1105-18. doi: 10.1111/cmi.12264. Epub 2014 Feb 13. D-alanine modification of a protease-susceptible outer membrane component by the Bordetella pertussis dra locus promotes resistance to antimicrobial peptides and polymorphonuclear leukocyte-mediated killing.Taneja NK, Ganguly T, Bakaletz LO, Nelson KJ, Dubey P, Poole LB, Deora R.J Bacteriol. 2013 Nov;195(22):5102-11. doi: 10.1128/JB.00510-13. Epub 2013 Sep 6. The genetic composition of Oxalobacter formigenes and its relationship to colonization and calcium oxalate stone disease.Knight J, Deora R, Assimos DG, Holmes RP.Urolithiasis. 2013 Jun;41(3):187-96. doi: 10.1007/s00240-013-0566-7. Epub 2013 Apr 30. Review.

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