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Full-Text Articles in Medicine and Health Sciences
Anti-Class Ii Monoclonal Antibody-Targeted Vibrio Cholerae Tcpa Pilin: Modulation Of Serologic Response, Epitope Specificity, And Isotype, Jia-Yan Wu, Ronald K. Taylor, William F. Wade
Anti-Class Ii Monoclonal Antibody-Targeted Vibrio Cholerae Tcpa Pilin: Modulation Of Serologic Response, Epitope Specificity, And Isotype, Jia-Yan Wu, Ronald K. Taylor, William F. Wade
Dartmouth Scholarship
Toxin-coregulated pilus (TCP) is a colonization factor required for cholera infection. It is not a strong immunogen when delivered in the context of whole cells, yet pilus subunits or TcpA derivative synthetic peptides induce protective responses. We examined the efficacy of immunizing mice with TCP conjugated to anti-class II monoclonal antibodies (MAb) with or without the addition of cholera toxin (CT) or anti-CD40 MAb to determine if the serologic response to TcpA could be manipulated. Anti-class II MAb-targeted TCP influenced the anti-TCP peptide serologic response with respect to titer and isotype. Responses to TcpA peptide 4 were induced with class …
Evaluation Of A Tetracycline-Inducible Promoter In Staphylococcus Aureus In Vitro And In Vivo And Its Application In Demonstrating The Role Of Sigb In Microcolony Formation, B. T. Bateman, N. P. Donegan, T. M. Jarry, M. Palma
Evaluation Of A Tetracycline-Inducible Promoter In Staphylococcus Aureus In Vitro And In Vivo And Its Application In Demonstrating The Role Of Sigb In Microcolony Formation, B. T. Bateman, N. P. Donegan, T. M. Jarry, M. Palma
Dartmouth Scholarship
An inducible promoter system provides a powerful tool for studying the genetic basis for virulence. A variety of inducible systems have been used in other organisms, including pXyl-xylR-inducible promoter, the pSpac-lacI system, and the arabinose-inducible PBAD promoter, but each of these systems has limitations in its application to Staphylococcus aureus. In this study, we demonstrated the efficacy of a tetracycline-inducible promoter system in inducing gene expression in S. aureus in vitro and inside epithelial cells as well as in an animal model of infection. Using the xyl/tetO promoter::gfpuvr fusion carried on a shuttle …
Evaluation Of Cholera Vaccines Formulated With Toxin-Coregulated Pilin Peptide Plus Polymer Adjuvant In Mice, Jia-Yan Wu, William F. Wade, Ronald K. Taylor
Evaluation Of Cholera Vaccines Formulated With Toxin-Coregulated Pilin Peptide Plus Polymer Adjuvant In Mice, Jia-Yan Wu, William F. Wade, Ronald K. Taylor
Dartmouth Scholarship
Cholera is an acute diarrheal disease that is caused by the gram-negative bacterium Vibrio cholerae. The low efficacy of currently available killed-whole-cell vaccines and the reactinogenicity coupled with potential reversion of live vaccines have thus far precluded widespread vaccination for the control of cholera. Recent studies on the molecular nature of the virulence components that contribute to V. cholerae pathogenesis have provided insights into possible approaches for the development of a defined subunit cholera vaccine. Genetic analysis has demonstrated that the toxin-coregulated pilus (TCP) is the major factor that contributes to colonization of the human intestine by V. cholerae. In …
Immune Response Genes Modulate Serologic Responses To Vibrio Cholerae Tcpa Pilin Peptides, Michael D. Meeks, Terri K. Wade, Ronald K. Taylor, William F. Wade
Immune Response Genes Modulate Serologic Responses To Vibrio Cholerae Tcpa Pilin Peptides, Michael D. Meeks, Terri K. Wade, Ronald K. Taylor, William F. Wade
Dartmouth Scholarship
Cholera is an enteric disease caused by Vibrio cholerae. Toxin-coregulated pilus (TCP), a type 4 pilus expressed by V. cholerae, is a cholera virulence factor that is required for host colonization. The TCP polymer is composed of subunits of TcpA pilin. Antibodies directed against TcpA are protective in animal models of cholera. While natural or recombinant forms of TcpA are difficult to purify to homogeneity, it is anticipated that synthesized TcpA peptides might serve as immunogens in a subunit vaccine. We wanted to assess the potential for effects of the immune response (Ir) gene that could complicate a peptide-based …
Sart, A Repressor Of Α-Hemolysin In Staphylococcus Aureus, Katherine A. Schmidt, Adhar C. Manna, Steven Gill, Ambrose L. Cheung
Sart, A Repressor Of Α-Hemolysin In Staphylococcus Aureus, Katherine A. Schmidt, Adhar C. Manna, Steven Gill, Ambrose L. Cheung
Dartmouth Scholarship
In searching the Staphylococcus aureus genome, we found several homologs to SarA. One of these genes, sarT, codes for a basic protein with 118 residues and a predicted molecular size of 16,096 Da. Northern blot analysis revealed that the expression of sarT was repressed by sarA and agr. An insertion sarT mutant generated in S. aureus RN6390 and 8325-4 backgrounds revealed minimal effect on the expression of sarR and sarA. The RNAIII level was notably increased in the sarT mutant, particularly in postexponential-phase cells, while the augmentative effect on RNAII was less. SarT repressed the expression of alpha-hemolysin, as determined …
Sars, A Sara Homolog Repressible By Agr, Is An Activator Of Protein A Synthesis In Staphylococcus Aureus, Ambrose L. Cheung, Katherine Schmidt, Brian Bateman, Adhar C. Manna
Sars, A Sara Homolog Repressible By Agr, Is An Activator Of Protein A Synthesis In Staphylococcus Aureus, Ambrose L. Cheung, Katherine Schmidt, Brian Bateman, Adhar C. Manna
Dartmouth Scholarship
The expression of protein A (spa) is repressed by global regulatory loci sarA and agr. Although SarA may directly bind to the spa promoter to downregulate spa expression, the mechanism by which agr represses spa expression is not clearly understood. In searching for SarA homologs in the partially released genome, we found a SarA homolog, encoding a 250-amino-acid protein designated SarS, upstream of the spa gene. The expression of sarS was almost undetectable in parental strain RN6390 but was highly expressed in agr and sarA mutants, strains normally expressing high level of protein A. Interestingly, protein A …
Characterization Of Sarr, A Modulator Of Sar Expression In Staphylococcus Aureus, Adhar Manna, Ambrose L. Cheung
Characterization Of Sarr, A Modulator Of Sar Expression In Staphylococcus Aureus, Adhar Manna, Ambrose L. Cheung
Dartmouth Scholarship
The expression of virulence determinants in Staphylococcus aureus is controlled by global regulatory loci (e.g., sar and agr). The sar locus is composed of three overlapping transcripts (sar P1, P3, and P2 transcripts from P1, P3, and P2 promoters, respectively), all encoding the 372-bp sarA gene. The level of SarA, the major regulatory protein, is partially controlled by the differential activation of sar promoters. We previously partially purified a ∼12 kDa protein with a DNA-specific column