Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 26 of 26
Full-Text Articles in Medicine and Health Sciences
Nonreplicating, Cyst-Defective Type Ii Toxoplasma Gondii Vaccine Strains Stimulate Protective Immunity Against Acute And Chronic Infection, Barbara Andrea Fox, David J. Bzik
Nonreplicating, Cyst-Defective Type Ii Toxoplasma Gondii Vaccine Strains Stimulate Protective Immunity Against Acute And Chronic Infection, Barbara Andrea Fox, David J. Bzik
Dartmouth Scholarship
Live attenuated vaccine strains, such as type I nonreplicating uracil auxotroph mutants, are highly effective in eliciting lifelong immunity to virulent acute infection by Toxoplasma gondii. However, it is currently unknown whether vaccine-elicited immunity can provide protection against acute infection and also prevent chronic infection. To address this problem, we developed nonreverting, nonreplicating, live attenuated uracil auxotroph vaccine strains in the type II Δku80 genetic background by targeting the deletion of the orotidine 5′-monophosphate decarboxylase (OMPDC) and uridine phosphorylase (UP) genes. Deletion of OMPDC induced a severe uracil auxotrophy with loss of replication, loss of …
In Vivo Cigarette Smoke Exposure Decreases Ccl20, Slpi, And Bd-1 Secretion By Human Primary Nasal Epithelial Cells, James Jukosky, Benoit J. Gosselin, Leah Foley, Tenzin Dechen, Steven Fiering, Mardi A. Crane-Godreau
In Vivo Cigarette Smoke Exposure Decreases Ccl20, Slpi, And Bd-1 Secretion By Human Primary Nasal Epithelial Cells, James Jukosky, Benoit J. Gosselin, Leah Foley, Tenzin Dechen, Steven Fiering, Mardi A. Crane-Godreau
Dartmouth Scholarship
Smokers and individuals exposed to second-hand cigarette smoke have a higher risk of developing chronic sinus and bronchial infections. This suggests that cigarette smoke (CS) has adverse effects on immune defenses against pathogens. Epithelial cells are important in airway innate immunity and are the first line of defense against infection. Airway epithelial cells not only form a physical barrier but also respond to the presence of microbes by secreting antimicrobials, cytokines, and chemokines. These molecules can lyse infectious microorganisms and/or provide signals critical to the initiation of adaptive immune responses. We examined the effects of CS on antimicrobial secretions of …
Acidosis Potentiates The Host Proinflammatory Interleukin-1Β Response To Pseudomonas Aeruginosa Infection, I. M. Torres, Y. R. Patankar, Tamer B. Shabaneh, E. Dolben, Deborah Hogan, David Leib, Brent L. Berwin
Acidosis Potentiates The Host Proinflammatory Interleukin-1Β Response To Pseudomonas Aeruginosa Infection, I. M. Torres, Y. R. Patankar, Tamer B. Shabaneh, E. Dolben, Deborah Hogan, David Leib, Brent L. Berwin
Dartmouth Scholarship
Infection by Pseudomonas aeruginosa, and bacteria in general, frequently promotes acidification of the local microenvironment, and this is reinforced by pulmonary exertion and exacerbation. However, the consequence of an acidic environment on the host inflammatory response to P. aeruginosa infection is poorly understood. Here we report that the pivotal cellular and host proinflammatory interleukin-1β (IL-1β) response, which enables host clearance of the infection but can produce collateral inflammatory damage, is increased in response to P. aeruginosa infection within an acidic environment. Synergistic mechanisms that promote increased IL-1β release in response to P. aeruginosa infection in an acidic environment are …
Intrinsic Innate Immunity Fails To Control Herpes Simplex Virus And Vesicular Stomatitis Virus Replication In Sensory Neurons And Fibroblasts, Pamela C. Rosato, David A. Leib
Intrinsic Innate Immunity Fails To Control Herpes Simplex Virus And Vesicular Stomatitis Virus Replication In Sensory Neurons And Fibroblasts, Pamela C. Rosato, David A. Leib
Dartmouth Scholarship
Herpes simplex virus 1 (HSV-1) establishes lifelong latent infections in the sensory neurons of the trigeminal ganglia (TG), wherein it retains the capacity to reactivate. The interferon (IFN)-driven antiviral response is critical for the control of HSV-1 acute replication. We therefore sought to further investigate this response in TG neurons cultured from adult mice deficient in a variety of IFN signaling components. Parallel experiments were also performed in fibroblasts isolated concurrently. We showed that HSV-1 replication was comparable in wild-type (WT) and IFN signaling-deficient neurons and fibroblasts. Unexpectedly, a similar pattern was observed for the IFN-sensitive vesicular stomatitis virus (VSV). …
An Inside Job: Hacking Into Janus Kinase/Signal Transducer And Activator Of Transcription Signaling Cascades By The Intracellular Protozoan Toxoplasma Gondii, Eric Y. Denkers, David J. Bzik, Barbara A. Fox, Barbara A. Butcher
An Inside Job: Hacking Into Janus Kinase/Signal Transducer And Activator Of Transcription Signaling Cascades By The Intracellular Protozoan Toxoplasma Gondii, Eric Y. Denkers, David J. Bzik, Barbara A. Fox, Barbara A. Butcher
Dartmouth Scholarship
The intracellular protozoan Toxoplasma gondii is well known for its skill at invading and living within host cells. New discoveries are now also revealing the astounding ability of the parasite to inject effector proteins into the cytoplasm to seize control of the host cell. This review summarizes recent advances in our understanding of one such secretory protein called ROP16. This molecule is released from rhoptries into the host cell during invasion. The ROP16 molecule acts as a kinase, directly activating both signal transducer and activator of transcription 3 (STAT3) and STAT6 signaling pathways. In macrophages, an important and preferential target …
Step-Wise Loss Of Bacterial Flagellar Torsion Confers Progressive Phagocytic Evasion, Rustin R. Lovewell, Ryan M. Collins, Julie L. Acker, George A. O'Toole, Matthew J. Wargo, Brent Berwin, Craig R. Roy
Step-Wise Loss Of Bacterial Flagellar Torsion Confers Progressive Phagocytic Evasion, Rustin R. Lovewell, Ryan M. Collins, Julie L. Acker, George A. O'Toole, Matthew J. Wargo, Brent Berwin, Craig R. Roy
Dartmouth Scholarship
Phagocytosis of bacteria by innate immune cells is a primary method of bacterial clearance during infection. However, the mechanisms by which the host cell recognizes bacteria and consequentially initiates phagocytosis are largely unclear. Previous studies of the bacterium Pseudomonas aeruginosa have indicated that bacterial flagella and flagellar motility play an important role in colonization of the host and, importantly, that loss of flagellar motility enables phagocytic evasion. Here we use molecular, cellular, and genetic methods to provide the first formal evidence that phagocytic cells recognize bacterial motility rather than flagella and initiate phagocytosis in response to this motility. We demonstrate …
The Pseudomonas Aeruginosa Magnesium Transporter Mgte Inhibits Transcription Of The Type Iii Secretion System, Gregory G. Anderson, Timothy L. Yahr, Rustin R. Lovewell, George A. O'Toole
The Pseudomonas Aeruginosa Magnesium Transporter Mgte Inhibits Transcription Of The Type Iii Secretion System, Gregory G. Anderson, Timothy L. Yahr, Rustin R. Lovewell, George A. O'Toole
Dartmouth Scholarship
Pseudomonas aeruginosa is an opportunistic pathogen that causes life-long pneumonia in individuals with cystic fibrosis (CF). These long-term infections are maintained by bacterial biofilm formation in the CF lung. We have recently developed a model of P. aeruginosa biofilm formation on cultured CF airway epithelial cells. Using this model, we discovered that mutation of a putative magnesium transporter gene, called mgtE, led to increased cytotoxicity of P. aeruginosa toward epithelial cells. This altered toxicity appeared to be dependent upon expression of the type III secretion system (T3SS). In this study, we found that mutation of mgtE results in increased T3SS …
Salicylic Acid Diminishes Staphylococcus Aureus Capsular Polysaccharide Type 5 Expression, Lucia P. Alvarez, Maria S. Barbagelata, Mariana Gordiola, A. L. Cheung
Salicylic Acid Diminishes Staphylococcus Aureus Capsular Polysaccharide Type 5 Expression, Lucia P. Alvarez, Maria S. Barbagelata, Mariana Gordiola, A. L. Cheung
Dartmouth Scholarship
Capsular polysaccharides (CP) of serotypes 5 (CP5) and 8 (CP8) are major Staphylococcus aureus virulence factors. Previous studies have shown that salicylic acid (SAL), the main aspirin metabolite, affects the expression of certain bacterial virulence factors. In the present study, we found that S. aureus strain Reynolds (CP5) cultured with SAL was internalized by MAC-T cells in larger numbers than strain Reynolds organisms not exposed to SAL. Furthermore, the internalization of the isogenic nonencapsulated Reynolds strain into MAC-T cells was not significantly affected by preexposure to SAL. Pretreatment of S. aureus strain Newman with SAL also enhanced internalization into MAC-T …
Role Of Pknb Kinase In Antibiotic Resistance And Virulence In Community-Acquired Methicillin-Resistant Staphylococcus Aureus Strain Usa300, S. Tamber, J. Schwartzman, A. L. Cheung
Role Of Pknb Kinase In Antibiotic Resistance And Virulence In Community-Acquired Methicillin-Resistant Staphylococcus Aureus Strain Usa300, S. Tamber, J. Schwartzman, A. L. Cheung
Dartmouth Scholarship
The regulation of cellular processes by eukaryote-like serine/threonine kinases is widespread in bacteria. In the last 2 years, several studies have examined the role of serine/threonine kinases in Staphylococcus aureus on cell wall metabolism, autolysis, and virulence, mostly in S. aureus laboratory isolates in the 8325-4 lineage. In this study, we showed that the pknB gene (also called stk1) of methicillin-resistant S. aureus (MRSA) strain COL and the community-acquired MRSA (CA-MRSA) strain USA300 is involved in cell wall metabolism, with the pknB mutant exhibiting enhanced sensitivity to β-lactam antibiotics but not to other classes of antibiotics, including aminoglycosides, ciprofloxacin, …
Long-Term Immunity To Lethal Acute Or Chronic Type Ii Toxoplasma Gondii Infection Is Effectively Induced In Genetically Susceptible C57bl/6 Mice By Immunization With An Attenuated Type I Vaccine Strain, Jason P. Gigley, Barbara A. Fox, David J. Bzik
Long-Term Immunity To Lethal Acute Or Chronic Type Ii Toxoplasma Gondii Infection Is Effectively Induced In Genetically Susceptible C57bl/6 Mice By Immunization With An Attenuated Type I Vaccine Strain, Jason P. Gigley, Barbara A. Fox, David J. Bzik
Dartmouth Scholarship
C57BL/6 (B6) mice are genetically highly susceptible to chronic type II Toxoplasma gondii infections that invariably cause lethal toxoplasmic encephalitis. We examined the ability of an attenuated type I vaccine strain to elicit long-term immunity to lethal acute or chronic type II infections in susceptible B6 mice. Mice immunized with the type I cps1-1 vaccine strain were not susceptible to a lethal (100-cyst) challenge with the type II strain ME49. Immunized mice challenged with 10 ME49 cysts exhibited significant reductions in brain cyst and parasite burdens compared to naive mice, regardless of the route of challenge infection. Remarkably, cps1-1 strain-immunized …
Flagellum-Mediated Biofilm Defense Mechanisms Of Pseudomonas Aeruginosa Against Host-Derived Lactoferrin, Jeff G. Leid, Mathias Kerr, Candice Selgado, Chelsa Johnson, Gabriel Moreno, Alyssa Smith, Mark E. Shirtliff, Georg A. O'Toole, Emily K. Cope
Flagellum-Mediated Biofilm Defense Mechanisms Of Pseudomonas Aeruginosa Against Host-Derived Lactoferrin, Jeff G. Leid, Mathias Kerr, Candice Selgado, Chelsa Johnson, Gabriel Moreno, Alyssa Smith, Mark E. Shirtliff, Georg A. O'Toole, Emily K. Cope
Dartmouth Scholarship
Chronic infection with the gram-negative organism Pseudomonas aeruginosa is a leading cause of morbidity and mortality in human patients, despite high doses of antibiotics used to treat the various diseases this organism causes. These infections are chronic because P. aeruginosa readily forms biofilms, which are inherently resistant to antibiotics as well as the host's immune system. Our laboratory has been investigating specific mutations in P. aeruginosa that regulate biofilm bacterial susceptibility to the host. To continue our investigation of the role of genetics in bacterial biofilm host resistance, we examined P. aeruginosa biofilms that lack the flgK gene. This mutant …
Genetic Evidence For An Alternative Citrate-Dependent Biofilm Formation Pathway In Staphylococcus Aureus That Is Dependent On Fibronectin Binding Proteins And The Grars Two-Component Regulatory System, Robert M. Q. Shanks, Michael A. Meehl, Kimberly M. Brothers, Raquel M. Martinez, Niles P. Donegan, Martha L. Graber, Ambrose L. Cheung, George A. O'Toole
Genetic Evidence For An Alternative Citrate-Dependent Biofilm Formation Pathway In Staphylococcus Aureus That Is Dependent On Fibronectin Binding Proteins And The Grars Two-Component Regulatory System, Robert M. Q. Shanks, Michael A. Meehl, Kimberly M. Brothers, Raquel M. Martinez, Niles P. Donegan, Martha L. Graber, Ambrose L. Cheung, George A. O'Toole
Dartmouth Scholarship
We reported previously that low concentrations of sodium citrate strongly promote biofilm formation by Staphylococcus aureus laboratory strains and clinical isolates. Here, we show that citrate promotes biofilm formation via stimulating both cell-to-surface and cell-to-cell interactions. Citrate-stimulated biofilm formation is independent of the ica locus, and in fact, citrate represses polysaccharide adhesin production. We show that fibronectin binding proteins FnbA and FnbB and the global regulator SarA, which positively regulates fnbA and fnbB gene expression, are required for citrate's positive effects on biofilm formation, and citrate also stimulates fnbA and fnbB gene expression. Biofilm formation is also stimulated by several …
Transcutaneous Immunization With Toxin-Coregulated Pilin A Induces Protective Immunity Against Vibrio Cholerae O1 El Tor Challenge In Mice, Julianne E. Rollenhagen, Anuj Kalsy, Francisca Cerda, Manohar John
Transcutaneous Immunization With Toxin-Coregulated Pilin A Induces Protective Immunity Against Vibrio Cholerae O1 El Tor Challenge In Mice, Julianne E. Rollenhagen, Anuj Kalsy, Francisca Cerda, Manohar John
Dartmouth Scholarship
Toxin-coregulated pilin A (TcpA) is the main structural subunit of a type IV bundle-forming pilus of Vibrio cholerae, the cause of cholera. Toxin-coregulated pilus is involved in formation of microcolonies of V. cholerae at the intestinal surface, and strains of V. cholerae deficient in TcpA are attenuated and unable to colonize intestinal surfaces. Anti-TcpA immunity is common in humans recovering from cholera in Bangladesh, and immunization against TcpA is protective in murine V. cholerae models. To evaluate whether transcutaneously applied TcpA is immunogenic, we transcutaneously immunized mice with 100 mug of TcpA or TcpA with an immunoadjuvant (cholera toxin [CT], …
Prophylaxis And Therapy Of Inhalational Anthrax By A Novel Monoclonal Antibody To Protective Antigen That Mimics Vaccine-Induced Immunity, Laura Vitale, Diann Blanset, Israel Lowy, Thomas O'Neill, Joel Goldstein, Stephen F. Little, Gerard P. Andrews, Gary Dorough, Ronald K. Taylor, Tibor Keler
Prophylaxis And Therapy Of Inhalational Anthrax By A Novel Monoclonal Antibody To Protective Antigen That Mimics Vaccine-Induced Immunity, Laura Vitale, Diann Blanset, Israel Lowy, Thomas O'Neill, Joel Goldstein, Stephen F. Little, Gerard P. Andrews, Gary Dorough, Ronald K. Taylor, Tibor Keler
Dartmouth Scholarship
The neutralizing antibody response to the protective antigen (PA) component of anthrax toxin elicited by approved anthrax vaccines is an accepted correlate for vaccine-mediated protection against anthrax. We reasoned that a human anti-PA monoclonal antibody (MAb) selected on the basis of superior toxin neutralization activity might provide potent protection against anthrax. The fully human MAb (also referred to as MDX-1303 or Valortim) was chosen from a large panel of anti-PA human MAbs generated using transgenic mice immunized with recombinant PA solely on the basis of in vitro anthrax toxin neutralization. This MAb was effective in prophylactic and postsymptomatic treatment of …
Staphylococcus Aureus Escapes More Efficiently From The Phagosome Of A Cystic Fibrosis Bronchial Epithelial Cell Line Than From Its Normal Counterpart, Todd M. Jarry, Ambrose L. Cheung
Staphylococcus Aureus Escapes More Efficiently From The Phagosome Of A Cystic Fibrosis Bronchial Epithelial Cell Line Than From Its Normal Counterpart, Todd M. Jarry, Ambrose L. Cheung
Dartmouth Scholarship
Staphylococcus aureus is frequently the initial bacterium isolated from young cystic fibrosis (CF) patients, and yet its role in CF disease progression has not been determined. Recent data from our lab demonstrates that S. aureus can invade and replicate within the CF tracheal epithelial cell line (CFT-1). Here we describe the finding that the fate of internalized S. aureus in CFT-1 cells differs from its complemented counterpart (LCFSN). S. aureus strain RN6390 was able to replicate within the mutant CFT-1 cells after invasion but not in the complemented LCFSN cells. At 1 h postinvasion, S. aureus containing vesicles within both …
Experimental Ocular Toxoplasmosis In Genetically Susceptible And Resistant Mice, Fangli Lu, Shiguang Huang, Mark S. Hu, Lloyd H. Kasper
Experimental Ocular Toxoplasmosis In Genetically Susceptible And Resistant Mice, Fangli Lu, Shiguang Huang, Mark S. Hu, Lloyd H. Kasper
Dartmouth Scholarship
Genetic factors determining the pathogenesis and course of ocular toxoplasmosis are poorly understood. In this study, we explored the development of experimental ocular pathogenesis in genetically dissimilar mice infected with either the RH strain, the PLK strain, or the immunodominant surface antigen 1 (SAG1 [P30])-deficient mutant of the RH strain of Toxoplasma gondii. At 11 days postinfection, ocular infection of C57BL/6 mice with all of the strains of parasites resulted in severe inflammatory lesions and high numbers of parasites in eye tissue; less severe ocular lesions at earlier histopathology and prolonged survival were observed in this mouse strain infected …
Heparin Stimulates Staphylococcus Aureus Biofilm Formation, Robert M. Q. Shanks, Niles P. Donegan, Martha L. Graber, Sarah E. Buckingham, Michael Zegans, Ambrose Cheung, George A. O'Toole
Heparin Stimulates Staphylococcus Aureus Biofilm Formation, Robert M. Q. Shanks, Niles P. Donegan, Martha L. Graber, Sarah E. Buckingham, Michael Zegans, Ambrose Cheung, George A. O'Toole
Dartmouth Scholarship
Heparin, known for its anticoagulant activity, is commonly used in catheter locks. Staphylococcus aureus, a versatile human and animal pathogen, is commonly associated with catheter-related bloodstream infections and has evolved a number of mechanisms through which it adheres to biotic and abiotic surfaces. We demonstrate that heparin increased biofilm formation by several S. aureus strains. Surface coverage and the kinetics of biofilm formation were stimulated, but primary attachment to the surface was not affected. Heparin increased S. aureus cell-cell interactions in a protein synthesis-dependent manner. The addition of heparin rescued biofilm formation of hla, ica, and sarA …
Role Of The Distal Sara Promoters In Sara Expression In Staphylococcus Aureus, Ambrose L. Cheung, Adhar C. Manna
Role Of The Distal Sara Promoters In Sara Expression In Staphylococcus Aureus, Ambrose L. Cheung, Adhar C. Manna
Dartmouth Scholarship
The global regulatory locus sarA comprises a 375-bp open reading frame that is driven by three promoters, the proximal P1 and distal P3 and P2 promoters. We mutated the weaker P3 and P2 promoters to ascertain the effect of the change on SarA protein and target gene expression. Our results indicated that the solely active P1 promoter led to a lower SarA protein level, which has an effect on agr transcription and subsequently had corresponding effects on hla, sspA, and spa transcription, probably in both agr-independent and agr-dependent manners.
Thymidine-Dependent Staphylococcus Aureus Small-Colony Variants Are Associated With Extensive Alterations In Regulator And Virulence Gene Expression Profiles, Barbara C. Kahl, Gunnar Belling, Petra Becker, Indranil Chatterjee, Katrin Wardecki, Karin Hilgert, Ambrose Cheung
Thymidine-Dependent Staphylococcus Aureus Small-Colony Variants Are Associated With Extensive Alterations In Regulator And Virulence Gene Expression Profiles, Barbara C. Kahl, Gunnar Belling, Petra Becker, Indranil Chatterjee, Katrin Wardecki, Karin Hilgert, Ambrose Cheung
Dartmouth Scholarship
Chronic airway infection is a hallmark of cystic fibrosis (CF) and many CF patients are infected persistently by Staphylococcus aureus. Thymidine-dependent trimethoprim-sulfamethoxazole (SXT)-resistant S. aureus small-colony variants (SCVs), often in combination with isogenic normal S. aureus phenotypes, are highly prevalent and persistent in airway secretions of CF patients due to long-term SXT therapy (B. Kahl, M. Herrmann, A. S. Everding, H. G. Koch, K. Becker, E. Harms, R. A. Proctor, and G.
Rat/Mgra, A Regulator Of Autolysis, Is A Regulator Of Virulence Genes In Staphylococcus Aureus, Susham Ingavale, Willem Van Wamel, Thanh T. Luong, Chia Y. Lee, Ambrose L. Cheung
Rat/Mgra, A Regulator Of Autolysis, Is A Regulator Of Virulence Genes In Staphylococcus Aureus, Susham Ingavale, Willem Van Wamel, Thanh T. Luong, Chia Y. Lee, Ambrose L. Cheung
Dartmouth Scholarship
We have previously identified mgrA (rat) as a regulator of autolysis in Staphylococcus aureus. Besides its effect on autolytic activity, we recently found alterations in the expression of regulator and target virulence genes in the mgrA mutant. Northern analysis and transcription fusion assays showed that inactivation of mgrA has led to the downregulation of RNAIII of agr and hla and upregulation of sarS and spa. Although both SarA and agr are activators of α-hemolysin and a repressors of protein A synthesis, we found that the transcription of sarA was not affected in the mgrA mutant and …
Interleukin-17/Interleukin-17 Receptor-Mediated Signaling Is Important For Generation Of An Optimal Polymorphonuclear Response Against Toxoplasma Gondii Infection, Michelle N. Kelly, Jay K. Kolls, Kyle Happel, Joseph D. Schwartzman
Interleukin-17/Interleukin-17 Receptor-Mediated Signaling Is Important For Generation Of An Optimal Polymorphonuclear Response Against Toxoplasma Gondii Infection, Michelle N. Kelly, Jay K. Kolls, Kyle Happel, Joseph D. Schwartzman
Dartmouth Scholarship
We investigated the role of interleukin-17 (IL-17)/IL-17 receptor (IL-17R)-mediated signaling in the protective immunity against Toxoplasma gondii. IL-17R−/− mice developed a normal adaptive immunity against the parasite. However, increased mortality in the knockout animals can be attributed to a defect in the migration of polymorphonuclear leukocytes to infected sites during early infection.
The Major Subunit Of The Toxin-Coregulated Pilus Tcpa Induces Mucosal And Systemic Immunoglobulin A Immune Responses In Patients With Cholera Caused By Vibrio Cholerae O1 And O139, Muhammad Asaduzzaman, Edward T. Ryan, Manohar John, Long Hang, Ashraful I. Khan, A. S. G. Faruque, Ronald K. Taylor
The Major Subunit Of The Toxin-Coregulated Pilus Tcpa Induces Mucosal And Systemic Immunoglobulin A Immune Responses In Patients With Cholera Caused By Vibrio Cholerae O1 And O139, Muhammad Asaduzzaman, Edward T. Ryan, Manohar John, Long Hang, Ashraful I. Khan, A. S. G. Faruque, Ronald K. Taylor
Dartmouth Scholarship
Diarrhea caused by Vibrio cholerae is known to give long-lasting protection against subsequent life-threatening illness. The serum vibriocidal antibody response has been well studied and has been shown to correlate with protection. However, this systemic antibody response may be a surrogate marker for mucosal immune responses to key colonization factors of this organism, such as the toxin-coregulated pilus (TCP) and other factors. Information regarding immune responses to TCP, particularly mucosal immune responses, is lacking, particularly for patients infected with the El Tor biotype of V. cholerae O1 or V. cholerae O139 since highly purified TcpA from these strains has not …
Synthetic Fragments Of Vibrio Cholerae O1 Inaba O-Specific Polysaccharide Bound To A Protein Carrier Are Immunogenic In Mice But Do Not Induce Protective Antibodies, Michael D. Meeks, Rina Saksena, Xingquan Ma, Terri K. Wade, Ronald K. Taylor, Pavol Kováč, William F. Wade
Synthetic Fragments Of Vibrio Cholerae O1 Inaba O-Specific Polysaccharide Bound To A Protein Carrier Are Immunogenic In Mice But Do Not Induce Protective Antibodies, Michael D. Meeks, Rina Saksena, Xingquan Ma, Terri K. Wade, Ronald K. Taylor, Pavol Kováč, William F. Wade
Dartmouth Scholarship
Development of Vibrio cholerae lipopolysaccharide (LPS) as a cholera vaccine immunogen is justified by the correlation of vibriocidal anti-LPS response with immunity. Two V. cholerae O1 LPS serotypes, Inaba and Ogawa, are associated with endemic and pandemic cholera. Both serotypes induce protective antibody following infection or vaccination. Structurally, the LPSs that define the serotypes are identical except for the terminal perosamine moiety, which has a methoxyl group at position 2 in Ogawa but a hydroxyl group in Inaba. The terminal sugar of the Ogawa LPS is a protective B-cell epitope. We chemically synthesized the terminal hexasaccharides of V. cholerae serotype …
Combined Tlr And Cd40 Triggering Induces Potent Cd8+ T Cell Expansion With Variable Dependence On Type I Ifn, Cory L. Ahonen, Christie L. Doxsee, Sean M. M. Mcgurran, Tony R. Riter, William F. Wade, Richard J. Barth, John P. Vasilakos, Randolph J. Noelle, Ross M. Kedl
Combined Tlr And Cd40 Triggering Induces Potent Cd8+ T Cell Expansion With Variable Dependence On Type I Ifn, Cory L. Ahonen, Christie L. Doxsee, Sean M. M. Mcgurran, Tony R. Riter, William F. Wade, Richard J. Barth, John P. Vasilakos, Randolph J. Noelle, Ross M. Kedl
Dartmouth Scholarship
Toll-like receptors are important in the activation of innate immunity, and CD40 is a molecule critical for many T and B cell responses. Whereas agonists for either pathway have been used as vaccine adjuvants, we show that a combination of Toll-like receptor (TLR)7 and CD40 agonists synergize to stimulate CD8+ T cell responses 10–20-fold greater than the use of either agonist alone. Antigen-specific CD8+ T cells elicited from combination CD40/TLR7 treatment demonstrated both lytic activities and interferon (IFN)γ production and an enhanced secondary response to antigenic challenge. Agonists for TLRs 2/6, 3, 4, and 9 also synergized with …
Immune Responses Of Different Mouse Strains After Challenge With Equivalent Lethal Doses Of Toxoplasma Gondii, Y. H. Lee, L. H. Kasper
Immune Responses Of Different Mouse Strains After Challenge With Equivalent Lethal Doses Of Toxoplasma Gondii, Y. H. Lee, L. H. Kasper
Dartmouth Scholarship
Most immunological studies that utilize different strains of inbred mice following T. gondii infection fail to compensate for differences in host susceptibility to the size of the parasite innoculum. To address this concern, susceptible C57BL/6 and resistant CBA/J mice were orally infected with either an equivalent 50 % lethal dose (LD50) of brain cysts of the 76K strain of T. gondii (15 cysts in C57BL/6, 400 cysts in CBA/J) or the same dose of parasites in each mouse strain. C57BL/6 mice receiving 400 cysts (LD50 of CBA/J mice) died post infection, whereas CBA/J mice that received 15 …
Sart Influences Sars Expression In Staphylococcus Aureus, Katherine A. Schmidt, Adhar C. Manna, Ambrose L. Cheung
Sart Influences Sars Expression In Staphylococcus Aureus, Katherine A. Schmidt, Adhar C. Manna, Ambrose L. Cheung
Dartmouth Scholarship
Staphylococcus aureus is a gram-positive pathogen that is capable of expressing a variety of virulence proteins in response to environmental signals. Virulence protein expression in S. aureus is controlled by a network of regulatory loci including sarA and agr. The sarA/agr network is associated with the expression of cell wall-associated adhesins during exponential growth and the expression of secreted enzymes and toxins in the transition to post-exponential growth. A number of sarA homologs, including sarT and sarS, have been identified in the S. aureus genome. Previous studies have shown that sarA influences expression of both sarT and sarS in the …