Progress 06/01/06 to 05/31/11
Outputs
OUTPUTS: Training and mentoring: During the duration of the grant, the following personnel were trained and mentored by Dr. Deora: Postdoctoral fellows: Dr. Meenu Mishra, Dr. Manish Bhardwaj and Dr. Neetu Kumra Taneja. Graduate Students: Dr. Gina Parise (received her Ph. D. degree); Neelima Sukumar (received her Ph. D. degree), Cheraton Love (received her Ph. D. degree) and Matt Conover (received her Ph. D. degree). Undergraduate students: Anju Karki (currently a graduate student at Purdue University) and Ying Vang. Seminars: The PI Dr. Deora presented his research at the following institutes: March 2011, University of Nebraska medical centre, Omaha; November 2010, Microcon 10, IMAM, India; July 2010, Michelob Seminar; Cancer Center and Cancer Biology; WFUHS; Februray 2010, Pennsylvania state University; April 2009. University of Minneapolis; December 2008. Wake Forest Institute of Regenarative Medicine; August 2008. Microbial Functional Genomics Awardee Workshop, CSREES, USDA Washington DC; April 2008. North Dakota State University, Department of Veterinary and Microbiological Sciences; August 2007. Indian Institute of Microbial Technology, Chandigarh, India. Study section reviewer: Dr. Deora served as a reviewer for the American Heart Associations' Virology, Immunology and Microbial pathogenesis study section in April 2008 and for the BSC1 study sections in 2009, 2010 and 2011. Collaborations: We have initiated collaborations with Dr. Tracy Nicholson at the National Animal Disease Center; Ames, IA. This collaboration involves in utilizing DNA microarrays to determine the changes in expression profiles during the biofilm mode of growth. Patents: 2008. Role of the Bordetella Bps polysaccharide as a vaccine candidate. Deora, R., Parise, G., Love C. 2007. Role of a Bordetella outer-membrane protein BcfA in protective immunity and as a vaccine candidate. Deora, R., Mishra M., Sukumar, N., PARTICIPANTS: Postdoctoral fellows: Dr. Meenu Mishra, Dr. Manish Bhardwaj and Dr. Neetu Kumra Taneja. Graduate Students: Dr. Gina Parise; Neelima Sukumar, Cheraton Love and Matt Conover. Undergraduate students: Anju Karki and Ying Vang. TARGET AUDIENCES: Cheraton love, a graduate student involved with the project is African American. The target audiences were scientists, administrators, postgraduate scholars, graduate and undergraduate students. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period. PARTICIPANTS: During the duration of the grant, the following personnel were trained and mentored by Dr. Deora: Postdoctoral fellows: Dr. Meenu Mishra, Dr. Manish Bhardwaj and Dr. Neetu Kumra Taneja. Graduate Students: Dr. Gina Parise (received her Ph. D. degree); Neelima Sukumar (received her Ph. D. degree), Cheraton Love (received her Ph. D. degree) and Matt Conover (received her Ph. D. degree). Undergraduate students: Anju Karki (currently a graduate student at Purdue University) and Ying Vang. TARGET AUDIENCES: Cheraton love, a graduate student involved with the project is African American. The target audiences were scientists, administrators, postgraduate scholars, graduate and undergraduate students. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
Our results have provided important insights towards understanding the multifactorial nature of Bordetella-host interactions. We have been able to obtain a better understanding of how a single regulatory locus of Bordetella, the BvgAS locus directs the observed variations in signal-dependent gene expression patterns. Currently available and proposed vaccines against B. bronchiseptica include live, attenuated, heat killed or genetically modified bacteria. Some of the problems associated with these various whole-cell vaccination approaches include: persistence of the vaccine strain in animals, poor induction of protective immunity and/or an antibody response and retention of some of the virulence characteristics by the vaccine strains. We discovered novel virulence factors and survival strategies employed by B. bronchiseptica for maximal virulence and persistence. One of these proteins, BcfA has been shown by the PI to function as a protective antigen in mice and is currently being tested by two veterinary health companies as a potential acellular Bordetella vaccine for dogs. The data obtained as part of research funded from this grant underscores the potential utility of an acellular vaccine approach and the importance of BcfA as a critical protective antigen for B. bronchiseptica infections.
Publications
- 1. Conover MS, Mishra M, Deora R. Extracellular DNA Is Essential for Maintaining Bordetella Biofilm Integrity on Abiotic Surfaces and in the Upper Respiratory Tract of Mice. 2011. Plos One. 6(2): e16861.
- 2. Waligora EA, Ramsey DM, Pryor EE Jr, Lu H, Hollis T, Sloan GP, Deora R, Wozniak DJ. AmrZ beta-sheet residues are essential for DNA binding and transcriptional control of Pseudomonas aeruginosa virulence genes. 2010. J. Bacteriol. 192:5390-401
- 3. Conover MS, Sloan GP, Love CF, Sukumar N, Deora R. The Bps polysaccharide of Bordetella pertussis promotes colonization and biofilm formation in the nose by functioning as an adhesin. 2010. Mol Microbiol. 77(6):1439-55
- 4. Sukumar, N., Sloan, GP, Conover, M., Love, C., Mattoo, S., Kock, N.D., and Deora, R. Cross-species protection mediated by a Bordetella bronchiseptica strain lacking antigenic homologs present in the acellular pertussis vaccines. 2010. Infect. Immun. 78(5):2008-16
- 5. Sukumar, N., Love, C., Conover, M., Kock, N.D., Dubey, P. and Deora, R. Active and Passive Immunization with Bordetella Colonization Factor A (BcfA) Protects Mice against Respiratory Challenge with Bordetella bronchiseptica. 2009 Infect. Immun. 77:885-95
- 6. Matthysse AG, Deora R, Mishra M, Torres AG. 2008. The polysaccharides cellulose, poly-ss-1,6-N-acetyl-D-glucosamine, and colanic acid are required for optimal binding of E. coli O157:H7 strains to alfalfa sprouts and K12 strains to plastic but not for binding to epithelial cells. 2008. Appl. Environ. Microbiol. 74:2384-90
- 7. Sloan-Parise, G, Love, CF, Sukumar N, Mishra M, and Deora R. The Bordetella Bps Polysaccharide is Critical for Biofilm Development in the Mouse Respiratory Tract. 2007. J. Bacteriol. 189:8270-6
- 8. Inhibition of Pseudomonas aeruginosa Biofilm Formation with Bromoageliferin Analogs. R. W. Iii RW, Richards JJ, Parise G, Ballard TE, Zeng W, Deora R, Melander C. 2007. Journal of the American Chemical Society. 129:6966-7
- 9.Sukumar N, Mishra M, Sloan GP, Ogi T, Deora R. Differential Bvg-Phase Dependent Regulation and Combinatorial Role in Pathogenesis of Two Bordetella Paralogs, BipA and BcfA. 2007. J. Bacteriol. 189:750-60
- 10.Gina Parise, Meenu Mishra, Yoshikane Itoh, Tony Romeo and Deora R. Role of a Putative Polysaccharide Locus in Bordetella Biofilm Development. 2007. J. Bacteriol. 189:750-60
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Progress 06/01/07 to 05/31/08
Outputs
OUTPUTS: Training and mentoring: During this reporting period the following personnel were trained and mentored by Dr. Deora: Postdoctoral fellows: Dr. Meenu Mishra and Dr. Manish Bhardwaj. Graduate Students: Dr. Gina Parise (received her Ph. D. degree); Neelima Sukumar, Cheraton Love and Matt Conover. Undergraduate students: Anju Karki and Ying Vang. Seminars: The PI Dr. Deora presented his research at the following institutes: August 2007. Indian Institute of Microbial Technology, Chandigarh, India. April 2008: North Dakota State University, Department of Veterinary & Microbiological Sciences. Study section reviewer: Dr. Deora served as a reviewer for the American Heart Associations' Virology, Immunology and Microbial pathogenesis study section in April 2008. Collaborations:We have initiated a new collaboration with Dr. Tracy Nicholson at the National Animal Disease Center; Ames, IA. This collaboration involves in utilizing DNA microarrays to determine the changes in expression profiles during the biofilm mode of growth. Patents: 2008. Role of the Bordetella Bps polysaccharide as a vaccine candidate. Deora, R., Parise, G., Love C. 2007. Role of a Bordetella outer-membrane protein BcfA in protective immunity and as a vaccine candidate. Deora, R., Mishra M., Sukumar, N., PARTICIPANTS: Postdoctoral fellows: Dr. Meenu Mishra and Dr. Manish Bhardwaj. Graduate Students: Dr. Gina Parise; Neelima Sukumar, Cheraton Love and Matt Conover. Undergraduate students: Anju Karki and Ying Vang. TARGET AUDIENCES: Cheraton love, a graduate student involved with the project is African American. The traget audiences were scientists, adminstrators, postgraduate scholars, graduate and undergraduate students. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
Our results have provided important insights towards understanding the multifactorial nature of Bordetella-host interactions. We have been able to obtain a better understanding of how a single regulatory locus of Bordetella, the BvgAS locus directs the observed variations in signal-dependent gene expression patterns. Currently available and proposed vaccines against B. bronchiseptica include live, attenuated, heat killed or genetically modified bacteria. Some of the problems associated with these various whole-cell vaccination approaches include: persistence of the vaccine strain in animals, poor induction of protective immunity and/or an antibody response and retention of some of the virulence characteristics by the vaccine strains. The data obtained as part of research funded from this grant underscores the potential utility of an acellular vaccine approach and the importance of BcfA as a critical protective antigen for B. bronchiseptica infections.
Publications
- Matthysse AG, Deora R, Mishra M, Torres AG. 2008. The polysaccharides cellulose, poly-ss-1,6-N-acetyl-D-glucosamine, and colanic acid are required for optimal binding of E. coli O157:H7 strains to alfalfa sprouts and K12 strains to plastic but not for binding to epithelial cells. Appl. Environ. Microbiol. 74:2384-90
- Sloan-Parise, G, Love, CF, Sukumar N, Mishra M, and Deora R. The Bordetella Bps Polysaccharide is Critical for Biofilm Development in the Mouse Respiratory Tract. 2007. J. Bacteriol. 189:8270-6
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Progress 06/01/06 to 05/31/07
Outputs
The previously known Bordetella protein BipA shares at its amino terminus similarity with intimin proteins of enteropathogenic and enterohemorrhagic E. coli and with invasins of Yersinia species. Despite similarity to intimins and invasins, previous studies showed that BipA does not have a role in respiratory tract colonization. Since Bordetellae express multiple adhesins, we hypothesized that the absence of BipA in B. bronchiseptica could be compensated by either a known or yet to be identified alternative factor, thereby leading to no apparent effect on colonization. As part of the research funded from this grant, we identified a B. bronchiseptica ORF termed bcfA, which is a paralog of bipA. We have now shown that in contrast to maximal expression of bipA in the Bvgi phase, bcfA is expressed at high levels in both the Bvg+ and the Bvgi phases. We also found that BvgA and BvgA-P bind differentially to the bcfA promoter region. Our studies demonstrated that BcfA is
localized to the outer membrane and that it is expressed during animal infection. Finally, we have shown that while individual deletions of either bipA or bcfA does not significantly impact respiratory tract colonization, concomitant deletion of both results in a defect in colonization of the rat trachea. Our results thus highlight a combinatorial role for two paralogous proteins in mediating efficient respiratory tract colonization.
Impacts
Our results have provided important insights towards understanding the multifactorial nature of Bordetella-host interactions. We have been able to obtain a better understanding of how a single regulatory locus of Bordetella, the BvgAS locus directs the observed variations in signal-dependent gene expression patterns. We believe that our results will allow us to investigate the role of BcfA as a target for vaccine and therapeutics.
Publications
- Gina Parise, Meenu Mishra, Yoshikane Itoh, Tony Romeo and Deora R. Role of a Putative Polysaccharide Locus in Bordetella Biofilm Development. 2007. J. Bacteriol. 189:750-60.
- Sukumar N, Mishra M, Sloan GP, Ogi T, Deora R. Differential Bvg-Phase Dependent Regulation and Combinatorial Role in Pathogenesis of Two Bordetella Paralogs, BipA and BcfA. 2007. J. Bacteriol. 189:3695-704
- Inhibition of Pseudomonas aeruginosa Biofilm Formation with Bromoageliferin Analogs. 2007. R. W. Iii RW, Richards JJ, Parise G, Ballard TE, Zeng W, Deora R, Melander C. 2007. Journal of the American Chemical Society. 2007. 129:6966-7.
- The Bordetella Bps Polysaccharide is Critical for Biofilm Development in the Mouse Respiratory Tract. Sloan-Parise, G, Love, CF, Sukumar N, Mishra M, and Deora R. 2007. J. Bacteriol. In press.
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