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You searched for +publisher:"University of Texas Medical Branch – Galveston" +contributor:("Motin, Vladimir L"). Showing records 1 – 3 of 3 total matches.

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University of Texas Medical Branch – Galveston

1. [No author]. Carbon Catabolite Regulation of Yersinia pestis Pathogenesis .

Degree: University of Texas Medical Branch – Galveston

In order to survive in the unique environments associated with different aspects of the infectious cycle, Yersinia pestis evokes adaptive responses to concertedly regulate gene expression. The overall objective of this project was to ascertain the impact of carbon catabolite regulation upon Y. pestis pathogenesis. Specifically, this research encompassed two major aspects: 1) regulation of Y. pestis biofilm formation, a key transmission factor, and 2) characterization of carbon catabolite regulation amid conditions reflective of mammalian infection. Findings demonstrate that Y. pestis biofilm formation is subject to carbon catabolite regulation in which primary carbon sources inhibit biofilm production, and alternate carbon sources induce robust biofilm development. The differential modulation of Y. pestis biofilm production was found to be facilitated by the cAMP receptor protein, CRP. The microevolution of Y. pestis biovar Orientalis is characterized by loss of glycerol fermentation resulting from dysfunction of glpD and ensured by impairment of the glpFKX operon. Through a mode of action presumably independent of CRP regulation, glpD has been shown to promote Y. pestis biofilm production. Findings in this study also clarified conflicting observations made by independent investigative groups, indicating that the Hfq sRNA chaperone differentially modulates Y. pestis biofilm production in response to primary or alternate available carbon sources. The thermo-regulated sRNA species, Ysr172 and sR084, were shown to be dispensable for Y. pestis biofilm production. Contrary to what has been described for E. coli, the carbon storage regulator protein, CsrA, was found to be a positive regulator of Y. pestis biofilm formation. Loss of hmsP, encoding a cyclic diguanylate phosphodiesterase, restored biofilm production in a csrA-deficient mutant, providing insight regarding the mechanism of Y. pestis biofilm regulation. Deletion of csrA severely impaired Y. pestis growth in peptide-rich HIB at 37°C. Furthermore, loss of csrA resulted in a toxic effect at 37°C during growth in chemically defined BCS medium, regardless of available carbon source. Lethality was described for both pCD1 positive and negative Y. pestis strains, thereby refuting a low-calcium response (Lcr). Mutants deficient in csrA had reduced survival upon murine macrophage-like cell challenge, demonstrating CsrA may serve a crucial Y. pestis virulence regulator. Advisors/Committee Members: Motin, Vladimir L (advisor), Chopra, Ashok (committeeMember), Bouyer, Donald (committeeMember), Sahni, Sanjeev (committeeMember), Adkins, Joshua (committeeMember).

Subjects/Keywords: Yersinia pestis; CRP; CsrA; pathogenesis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

author], [. (n.d.). Carbon Catabolite Regulation of Yersinia pestis Pathogenesis . (Thesis). University of Texas Medical Branch – Galveston. Retrieved from http://hdl.handle.net/2152.3/732

Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

author], [No. “Carbon Catabolite Regulation of Yersinia pestis Pathogenesis .” Thesis, University of Texas Medical Branch – Galveston. Accessed July 17, 2019. http://hdl.handle.net/2152.3/732.

Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

author], [No. “Carbon Catabolite Regulation of Yersinia pestis Pathogenesis .” Web. 17 Jul 2019.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Vancouver:

author] [. Carbon Catabolite Regulation of Yersinia pestis Pathogenesis . [Internet] [Thesis]. University of Texas Medical Branch – Galveston; [cited 2019 Jul 17]. Available from: http://hdl.handle.net/2152.3/732.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.

Council of Science Editors:

author] [. Carbon Catabolite Regulation of Yersinia pestis Pathogenesis . [Thesis]. University of Texas Medical Branch – Galveston; Available from: http://hdl.handle.net/2152.3/732

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.


University of Texas Medical Branch – Galveston

2. [No author]. Construction, characterization, and evaluation of CLH001 as a vaccine candidate against respiratory glanders .

Degree: University of Texas Medical Branch – Galveston

Burkholderia mallei is the causative agent of glanders, an incapacitating disease with high mortality rates in respiratory cases. Its endemicity and ineffectual treatment options emphasize its public health threat and highlight the need for a vaccine. In this study, we constructed and characterized B. mallei ∆tonB ∆hcp1 (CLH001), a strain deficient in iron uptake and type six secretion functions, and investigated its ability to protect against acute respiratory glanders infection. When compared to wild-type (wt), CLH001 exhibited decreased growth kinetics in both culture media (LBG) and RAW 264.7 murine macrophages. Additionally unlike wt, CLH001 was deficient in Hcp1 production and was unable to induce multinucleated giant cells (MNGC) formation in both phagocytic and non-phagocytic cell lines. Intranasal (i.n.) administration of CLH001 (1.5x104 CFU) to BALB/c and NSG mice resulted in 100% survival with no detectable colonization or abnormal histopathology in the lungs, liver or spleen of vaccinated mice. BALB/c mice immunized i.n. with 1.5x105 CFU of CLH001 in a prime/boost regimen showed full protection post-challenge with 1.5x104 CFU of B. mallei lux wt strain. Organs from surviving mice were clear of bacterial colonization and histopathological abnormalities. Immunized mice showed high B. mallei-specific IgG serum titers and a Th1-biased response (IgG2a:IgG1 ratio = 4.0), a good predictor of protection. Additionally, pre-challenge sera displayed significant bactericidal activity over naïve serum (p=0.0062). Vaccinated BALB/c mice were also significantly protected (87.5% survival; p= < 0.0001) against higher dose (3.5x105 CFU) of B. mallei 23344 challenge. Our studies show that CLH001 is attenuated and safe, and effective at providing protection against lethal B. mallei challenge. CLH001 is not only a viable vaccine platform for advancement into pre-clinical studies, but also represents the first Tier 1 Select Agent-excluded B. mallei strain. Advisors/Committee Members: Torres, Alfredo G (advisor), Burtnick, Mary N (committeeMember), Endsley, Janice J (committeeMember), Motin, Vladimir L (committeeMember), Valbuena, Gustavo (committeeMember).

Subjects/Keywords: Glanders; Burkholderia mallei; vaccines; TonB; Type VI Secretion System; Hcp1

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

author], [. (n.d.). Construction, characterization, and evaluation of CLH001 as a vaccine candidate against respiratory glanders . (Thesis). University of Texas Medical Branch – Galveston. Retrieved from http://hdl.handle.net/2152.3/11151

Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

author], [No. “Construction, characterization, and evaluation of CLH001 as a vaccine candidate against respiratory glanders .” Thesis, University of Texas Medical Branch – Galveston. Accessed July 17, 2019. http://hdl.handle.net/2152.3/11151.

Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

author], [No. “Construction, characterization, and evaluation of CLH001 as a vaccine candidate against respiratory glanders .” Web. 17 Jul 2019.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Vancouver:

author] [. Construction, characterization, and evaluation of CLH001 as a vaccine candidate against respiratory glanders . [Internet] [Thesis]. University of Texas Medical Branch – Galveston; [cited 2019 Jul 17]. Available from: http://hdl.handle.net/2152.3/11151.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.

Council of Science Editors:

author] [. Construction, characterization, and evaluation of CLH001 as a vaccine candidate against respiratory glanders . [Thesis]. University of Texas Medical Branch – Galveston; Available from: http://hdl.handle.net/2152.3/11151

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.


University of Texas Medical Branch – Galveston

3. [No author]. Yersinia pestis CO92 mutant deleted for the genes encoding Braun lipoprotein and plasminogen activator protease: Characterization of a potential live-attenuated vaccine candidate .

Degree: University of Texas Medical Branch – Galveston

There is no FDA-approved vaccine against Yersinia pestis, the causative agent of bubonic and pneumonic plague. Since both humoral- and cell- mediated immunity are essential in providing protection to the host against plague, we developed a live-attenuated vaccine strain by deleting Braun lipoprotein (lpp) and plasminogen-activating protease (pla) genes from Y. pestis CO92. The lpp pla double isogenic mutant was highly attenuated in evoking both bubonic and pneumonic plague in a mouse model. Further, animals immunized with the mutant by either the intranasal or the subcutaneous routes were significantly protected from developing subsequent pneumonic plague. In mice, the mutant poorly disseminated to peripheral organs and the production of pro-inflammatory cytokines concurrently decreased. Histopathologically, reduced damage to the lungs and liver of mice infected with the lpp pla double mutant was observed when compared to the WT CO92-challenged animals. The lpp pla mutant-immunized mice elicited a humoral immune response to the WT bacterium, as well as to CO92-specific antigens. Moreover, T cells from the mutant-immunized animals exhibited significantly higher proliferative responses when stimulated ex vivo with the heat-killed WT CO92 antigens, compared to responses in mice immunized with the same sub-lethal dose of WT CO92. Likewise, T cells from the mutant-immunized mice produced more IFN-γ and interleukin-4. These animals had an increasing number of TNF-α-producing CD4+ and CD8+ T cells compared to WT CO92-infected mice. These data emphasized the role of TNF-α and IFN-γ in protecting mice against pneumonic plague. Overall, our in vivo studies provided evidence that deletion of lpp and pla genes acted synergistically in protecting animals against pneumonic plague, and we have demonstrated an immunological basis for this protection. We further characterized the ∆lpp ∆pla double mutant in two murine macrophage cell lines as well as in primary human monocyte-derived macrophages to gauge its potential as a live-attenuated vaccine candidate. We first demonstrated that the ∆pla single and the ∆lpp ∆pla double mutant were unable to survive efficiently in murine and human macrophages, unlike WT CO92. We observed that the levels of Pla and its associated protease activity were not affected in the ∆lpp single mutant, and, likewise, deletion of the pla gene from WT CO92 did not alter Lpp levels. Further, our study revealed that both Lpp and Pla contributed to the intracellular survival of WT CO92 via different mechanisms. Importantly, the ability of the ∆lpp ∆pla double mutant to be phagocytized by macrophages, to stimulate production of tumor necrosis factor-α and interleukin-6, and to activate the nitric oxide killing pathways of the host cells remained unaltered when compared to the WT CO92-infected macrophages. Finally, macrophages infected with either the WT CO92 or the ∆lpp ∆pla double mutant were equally efficient in their uptake of zymosan particles as determined by flow cytometric analysis. Overall, our data… Advisors/Committee Members: Chopra, Ashok K (advisor), Peterson, Johnny W (committeeMember), Motin, Vladimir L (committeeMember), Cong, Yingzi (committeeMember), Baze, Wallace B (committeeMember).

Subjects/Keywords: Yersinia pestis; vaccine development; plasminogen activator protease; Braun lipoprotein

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

author], [. (n.d.). Yersinia pestis CO92 mutant deleted for the genes encoding Braun lipoprotein and plasminogen activator protease: Characterization of a potential live-attenuated vaccine candidate . (Thesis). University of Texas Medical Branch – Galveston. Retrieved from http://hdl.handle.net/2152.3/726

Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

author], [No. “Yersinia pestis CO92 mutant deleted for the genes encoding Braun lipoprotein and plasminogen activator protease: Characterization of a potential live-attenuated vaccine candidate .” Thesis, University of Texas Medical Branch – Galveston. Accessed July 17, 2019. http://hdl.handle.net/2152.3/726.

Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

author], [No. “Yersinia pestis CO92 mutant deleted for the genes encoding Braun lipoprotein and plasminogen activator protease: Characterization of a potential live-attenuated vaccine candidate .” Web. 17 Jul 2019.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Vancouver:

author] [. Yersinia pestis CO92 mutant deleted for the genes encoding Braun lipoprotein and plasminogen activator protease: Characterization of a potential live-attenuated vaccine candidate . [Internet] [Thesis]. University of Texas Medical Branch – Galveston; [cited 2019 Jul 17]. Available from: http://hdl.handle.net/2152.3/726.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.

Council of Science Editors:

author] [. Yersinia pestis CO92 mutant deleted for the genes encoding Braun lipoprotein and plasminogen activator protease: Characterization of a potential live-attenuated vaccine candidate . [Thesis]. University of Texas Medical Branch – Galveston; Available from: http://hdl.handle.net/2152.3/726

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.

.