bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucuronoxylomannan, the Major Capsular Polysaccharide of
Cryptococcus neoformans
, Inhibits the Progression of Group B Streptococcal Arthritis
Authors: Tissi Luciana , Puliti Manuela , Bistoni Francesco , Mosci Paolo , Kozel Thomas R. , Vecchiarelli Anna 
Published: October 2004

ABSTRACT

Glucuronoxylomannan (GXM), the principal constituent of the
Cryptococcus neoformans
capsule, modulates the inflammatory response of human monocytes in vitro. Here we examine the efficacy of GXM as a novel anti-inflammatory compound for use against experimental septic arthritis. Arthritis was induced in mice by the intravenous injection of 8 × 10
6
CFU of type IV group B streptococcus (GBS). GXM was administered intravenously in different doses (50, 100, or 200 μg/mouse) 1 day before and 1 day after bacterial inoculation. GXM treatment markedly decreased the incidence and severity of articular lesions. Histological findings showed limited periarticular inflammation in the joints of GXM-treated mice, confirming the clinical observations. The amelioration of arthritis was associated with a significant reduction in the local production of interleukin-6 (IL-6), IL-1β, macrophage inflammatory protein 1α (MIP-1α), and MIP-2 and an increase in systemic IL-10 levels. Moreover, peritoneal macrophages derived from GXM-treated mice and stimulated in vitro with heat-inactivated GBS showed a similar pattern of cytokine production. The present study provides evidence for the modulation of the inflammatory response by GXM in vivo and suggests a potential therapeutic use for this compound in pathologies involving inflammatory processes.
Transcriptome of Uropathogenic
Escherichia coli
during Urinary Tract Infection
Authors: Snyder Jennifer A. , Haugen Brian J. , Buckles Eric L. , Lockatell C. Virginia , Johnson David E. , Donnenberg Michael S. , Welch Rodney A. , Mobley Harry L. T. 
Published: October 2004

ABSTRACT

A uropathogenic
Escherichia coli
strain CFT073-specific DNA microarray that includes each open reading frame was used to analyze the transcriptome of CFT073 bacteria isolated directly from the urine of infected CBA/J mice. The in vivo expression profiles were compared to that of
E. coli
CFT073 grown statically to exponential phase in rich medium, revealing the strategies this pathogen uses in vivo for colonization, growth, and survival in the urinary tract environment. The most highly expressed genes overall in vivo encoded translational machinery, indicating that the bacteria were in a rapid growth state despite specific nutrient limitations. Expression of type 1 fimbriae, a virulence factor involved in adherence, was highly upregulated in vivo. Five iron acquisition systems were all highly upregulated during urinary tract infection, as were genes responsible for capsular polysaccharide and lipopolysaccharide synthesis, drug resistance, and microcin secretion. Surprisingly, other fimbrial genes, such as
pap
and
foc/sfa
, and genes involved in motility and chemotaxis were downregulated in vivo.
E. coli
CFT073 grown in human urine resulted in the upregulation of iron acquisition, capsule, and microcin secretion genes, thus partially mimicking growth in vivo. On the basis of gene expression levels, the urinary tract appears to be nitrogen and iron limiting, of high osmolarity, and of moderate oxygenation. This study represents the first assessment of any
E. coli
pathotype's transcriptome in vivo and provides specific insights into the mechanisms necessary for urinary tract pathogenesis.
Listeria monocytogenes-Based Antibiotic Resistance Gene-Free Antigen Delivery System Applicable to Other Bacterial Vectors and DNA Vaccines
Authors: Verch Thorsten , Pan Zhen-Kun , Paterson Yvonne 
Published: October 2004

ABSTRACTPlasmids represent a powerful tool to rapidly introduce genes into bacteria and help them reach high expression levels. In vaccine development, with live vaccine vectors, this allows greater flexibility and the ability to induce larger antigen amounts through multiple gene copies. However, plasmid retention often requires antibiotic resistance markers, the presence of which has been discouraged in clinical applications by the Food and Drug Administration. Therefore, we developed aListeria monocytogenes-Escherichia colishuttle plasmid that is retained by complementation ofd-alanine racemase-deficient mutant strains both in vitro and in vivo. Our technology potentially allows the production of antibiotic resistance marker-free DNA vaccines as well as bacterial vaccine vectors devoid of engineered antibiotic resistances. As a proof of concept, we applied thed-alanine racemase complementation system to ourListeriacancer vaccine platform. With a transplantable tumor model, we compared the efficacy of the newListeriavector to that of an established vector containing a conventional plasmid carrying a tumor-specific antigen. Both vaccine vector systems resulted in long-term regression of established tumors, with no significant difference between them. Thus, theListeriavaccine vector presented here potentially complies with Food and Drug Administration regulations and could be developed further for clinical use.
Intact Gram-NegativeHelicobacter pylori,Helicobacter felis, andHelicobacter hepaticusBacteria Activate Innate Immunity via Toll-Like Receptor 2 but Not Toll-Like Receptor 4
Authors: Mandell Leisa , Moran Anthony P. , Cocchiarella Andrew , Houghton JeanMarie , Taylor Nancy , Fox James G. , Wang Timothy C. , Kurt-Jones Evelyn A. 
Published: October 2004

ABSTRACTMolecular and genetic studies have demonstrated that members of the Toll-like receptor (TLR) family are critical innate immune receptors. TLRs are recognition receptors for a diverse group of microbial ligands including bacteria, fungi, and viruses. This study demonstrates that distinct TLRs are responsible for the recognition ofHelicobacterlipopolysaccharide (LPS) versus intactHelicobacterbacteria. We show that the cytokine-inducing activity ofHelicobacterLPS was mediated by TLR4; i.e., TLR4-deficient macrophages were unresponsive toHelicobacter pyloriLPS. Surprisingly, the cytokine response to wholeHelicobacterbacteria (H. pylori,H. hepaticus, andH. felis) was mediated not by TLR4 but rather by TLR2. Studies of HEK293 transfectants revealed that expression of human TLR2 was sufficient to confer responsiveness to intactHelicobacterbacteria, but TLR4 transfection was not sufficient. Our studies further suggest thatcagpathogenicity island genes may modulate the TLR2 agonist activity ofH. pyloriascagA+bacteria were more active on a per-cell basis compared tocagAmutant bacteria for interleukin-8 (IL-8) cytokine secretion. Consistent with the transfection studies, analysis of knockout mice demonstrated that TLR2 was required for the cytokine response to intactHelicobacterbacteria. Macrophages from both wild-type and TLR4-deficient mice produced a robust cytokine secretion response (IL-6 and MCP-1) when stimulated with intactHelicobacterbacteria. In contrast, macrophages from TLR2-deficient mice were profoundly unresponsive to intactHelicobacterstimulation, failing to secrete cytokines even at high (100:1) bacterium-to-macrophage ratios. Our studies suggest that TLR2 may be the dominant innate immune receptor for recognition of gastrointestinalHelicobacterspecies.
Role of Protein Tyrosine Kinase p53/56lynin Diminished Lipopolysaccharide Priming of Formylmethionylleucyl- phenylalanine-Induced Superoxide Production in Human Newborn Neutrophils
Authors: Yan Sen Rong , Byers David M. , Bortolussi Robert 
Published: October 2004

ABSTRACTHuman newborns are more susceptible than adults to bacterial infection. With gram-negative bacteria, this may be due to a diminished response of newborn leukocytes to lipopolysaccharide (LPS). Since protein tyrosine kinase inhibition abolishes LPS priming in adult cells, we hypothesized that protein tyrosine kinases may have a critical role in LPS priming of polymorphonuclear neutrophils (PMNs) and that newborn PMNs may have altered protein tyrosine kinase activities. In the present study, we investigated the role ofsrcfamily protein tyrosine kinases in the LPS response of newborn PMNs compared to adult cells. In a respiratory assay, the LPS-primed increase in formylmethionylleucylphenylalanine (fMLP)-triggered O2−release by adult PMNs was greatly decreased by PP1 [4-amino-5-(4-methyphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine], asrckinase inhibitor, to the level of untreated newborn PMNs, in which LPS failed to prime. LPS activated thesrc-like kinases p59hck(HCK) and p58fgr(FGR) in both adult and newborn PMNs but increased the activation of p53/56lyn(LYN) only in adult cells. In newborn PMNs, LYN was highly phosphorylated independent of LPS. We evaluated subcellular fractions of PMNs and found that the phosphorylated form of LYN was mainly in the Triton-extractable, cytosolic fraction in adult PMNs, while in newborn cells it was located mainly in Triton-insoluble, granule- and membrane-associated fractions. In contrast, the phosphorylated mitogen-activated protein kinases ERK1/2 and p38 were mainly detected in the cytosol in both adult and newborn PMNs. These data indicate a role for LYN in the regulation of LPS priming. The trapping of phosphorylated LYN in the membrane-granule fraction in newborn PMNs may contribute to the deficiency of newborn cells in responding to LPS stimulation.
Application of Mycobacterial Proteomics to Vaccine Design: Improved Protection by
Mycobacterium bovis
BCG Prime-Rv3407 DNA Boost Vaccination against Tuberculosis
Authors: Mollenkopf Hans Joachim , Grode Leander , Mattow Jens , Stein Maik , Mann Peggy , Knapp Bernhard , Ulmer Jeffrey , Kaufmann Stefan H. E. 
Published: October 2004

ABSTRACT

Information from comparative proteome analysis of
Mycobacterium tuberculosis
and
Mycobacterium bovis
bacillus Calmette-Guérin (BCG) principally allows prediction of potential vaccine candidates. Thirty-six
M. tuberculosis
DNA vaccine candidates identified by comparative proteome analysis were evaluated in the mouse model for protection against low-dose aerosol
M. tuberculosis
infection. We identified the DNA vaccine candidate Rv3407 as a protective antigen and analyzed putative major histocompatibility complex class I epitopes by computational predictions and gamma interferon Elispot assays. Importantly, we discovered that the DNA vaccine Rv3407 improved the efficacy of BCG vaccination in a heterologous prime-boost vaccination protocol. Our data demonstrate the rationale of a combination of proteomics, epitope prediction, and broad screening of putative antigens for identification of novel DNA vaccine candidates. Furthermore, our experiments show that heterologous prime-boost vaccination with a defined antigen boost “on top” of a BCG primer provides superior protection against tuberculosis over vaccination with BCG alone.
Combined Vaccine Regimen Based on Parenteral Priming with a DNA Vaccine and Administration of an Oral Booster Consisting of a RecombinantSalmonella entericaSerovar Typhimurium Vaccine Strain for Immunization against Infection with Human-Derived EnterotoxigenicEscherichia coliStrains
Authors: Lásaro Marcio O. , Luiz Wilson B. , Sbrogio-Almeida Maria E. , Nishimura Lucilia S. , Guth Beatriz E. C. , Ferreira Luis C. S. 
Published: October 2004

ABSTRACTRepeated evidence has demonstrated that combined primer-booster immunization regimens can improve both secreted and humoral immune responses to antigens derived from viral, bacterial, and parasitic pathogens. For the present work, we evaluated the synergic serum immunoglobulin G (IgG) and fecal IgA antibody responses elicited in BALB/c mice who were intramuscularly primed with a DNA vaccine, pRECFA, followed by oral boosting with an attenuatedSalmonella entericaserovar Typhimurium vaccine (HG3) strain, with both vaccines encoding the structural subunit (CfaB) of the CFA/I fimbriae produced by human-derived enterotoxigenicEscherichia coli(ETEC) strains. The immunological properties of the vaccine regimen were evaluated according to the order of the administered vaccines, the nature of the oral antigen carrier, the age of the vaccinated animals, the interval between the priming and boosting doses, and the amount of injected DNA. The production of gamma interferon and the IgG2a subclass in serum indicated that mice immunized with the primer-booster regimen developed prevailing type 1 T-cell-dependent immune responses. The synergic effect of the vaccine regimen on the induced antibody responses was also revealed by its ability to block the adhesive properties of CFA/I fimbriae expressed by live bacteria, as shown by the inhibition of Caco-2 cell and human erythrocyte binding. Moreover, DBA2 newborn mice were protected from lethal challenges with a CFA/I+ETEC strain after the incubation of live bacteria with serum samples harvested from mice who were subjected to the primer-booster regimen. We propose, therefore, that the DNA primer-Salmonellabooster regimen represents an alternative for the development of vaccines requiring both mucosal and systemic antibody responses for immunological protection.
Development of Immunity to Serogroup B Meningococci during Carriage of
Neisseria meningitidis
in a Cohort of University Students
Authors: Jordens J. Zoe , Williams Jeannette N. , Jones Graeme R. , Christodoulides Myron , Heckels John E. 
Published: October 2004

ABSTRACT

Understanding the basis of protective immunity is a key requirement for the development of an effective vaccine against infection with
Neisseria meningitidis
of serogroup B. We have conducted a longitudinal study into the dynamics of meningococcal acquisition and carriage in first-year university students. The detection of carriage of serogroup B meningococci correlated with an increase in detection of serum bactericidal activity (SBA) against both colonizing and heterologous serogroup B strains. Once induced, SBA remained high throughout the study. Although students showed increases in antibodies reactive with capsular polysaccharide and lipopolysaccharide (LPS), these antibody responses were transitory, and their decline was not accompanied by a corresponding decline in SBA. In contrast, there was a significant correlation between the presence of antibodies to the PorA outer membrane protein and SBA against both homologous and heterologous strains. SBA induced by a PorA-negative mutant confirmed the contribution of PorA to heterologous activity. Increases in SBA against a range of serogroup B strains were also observed in students in whom no meningococcal carriage was detected. This heterologous protection could not be associated with the presence of antibodies reacting with capsule, LPS, PorA, PorB, Rmp, Opa, Opc, or pilin, demonstrating that other, as yet unidentified, antigens contribute to the development of immunity to serogroup B meningococci. Identification of such antigens with the ability to induce an effective cross-reactive bactericidal response to a range of strains would be a major step in the production of a universally effective vaccine against infections caused by serogroup B meningococci.
Expression of Heterologous Antigens in Commensal
Neisseria
spp.: Preservation of Conformational Epitopes with Vaccine Potential
Authors: O'Dwyer Clíona A. , Reddin Karen , Martin Denis , Taylor Stephen C. , Gorringe Andrew R. , Hudson Michael J. , Brodeur Bernard R. , Langford Paul R. , Kroll J. Simon 
Published: October 2004

ABSTRACT

Commensal neisseriae share with
Neisseria meningitidis
(meningococcus) a tendency towards overproduction of the bacterial outer envelope, leading to the formation and release during growth of outer membrane vesicles (OMVs). OMVs from both meningococci and commensal neisseriae have shown promise as vaccines to protect against meningococcal disease. We report here the successful expression at high levels of heterologous proteins in commensal neisseriae and the display, in its native conformation, of one meningococcal outer membrane protein vaccine candidate, NspA, in OMVs prepared from such a recombinant
Neisseria flavescens
strain. These NspA-containing OMVs conferred protection against otherwise lethal intraperitoneal challenge of mice with
N. meningitidis
serogroup B, and sera raised against them mediated opsonophagocytosis of meningococcal strains expressing this antigen. This development promises to facilitate the design of novel vaccines containing membrane protein antigens that are otherwise difficult to present in native conformation that provide cross-protective efficacy in the prevention of meningococcal disease.
Modeling the Development of Acquired Clinical Immunity to
Plasmodium falciparum
Malaria
Authors: Gatton Michelle L. , Cheng Qin 
Published: October 2004

ABSTRACT

Individuals living in regions where malaria is endemic develop an acquired immunity to malaria which enables them to remain asymptomatic while still carrying parasites. Field studies indicate that cumulative exposure to a variety of diverse
Plasmodium
parasites is required for the transition from symptomatic to asymptomatic malaria. This study used a simulation model of the within-host dynamics of
P. falciparum
to investigate the development of acquired clinical immunity under different transmission conditions and levels of parasite diversity. Antibodies developed to
P. falciparum
erythrocyte membrane protein 1 (PfEMP1), a clonally variant molecule, were assumed to be a key human immunological response to
P. falciparum
infection, along with responses to clonally conserved but polymorphic antigens. The time to the development of clinical immunity was found to be proportional to parasite diversity and inversely proportional to transmission intensity. The effect of early termination of symptomatic infections by chemotherapy was investigated and found not to inhibit the host's ability to develop acquired immunity. However, the time required to achieve this state was approximately double that compared to when no treatment was administered. This study demonstrates that an immune response primarily targeted against PfEMP1 has the ability to reduce clinical symptoms of infections irrespective of whether treatment is administered, supporting its role in the development of acquired clinical immunity. The results also illustrate a novel use for simulation models of
P. falciparum
infections, investigation of the influence of intervention strategies on the development of naturally acquired clinical immunity.
Enhanced Immunogenicity in the Murine Airway Mucosa with an AttenuatedSalmonellaLive Vaccine Expressing OprF-OprI fromPseudomonas aeruginosa
Authors: Arnold Heinz , Bumann Dirk , Felies Melanie , Gewecke Britta , Sörensen Meike , Gessner J. Engelbert , Freihorst Joachim , von Specht Bernd Ulrich , Baumann Ulrich 
Published: October 2004

ABSTRACTWe constructed an oral live vaccine based on the attenuatedaroAmutantSalmonella entericaserovar Typhimurium strain SL3261 expressing outer membrane proteins F and I (OprF-OprI) fromPseudomonas aeruginosaand investigated it in a mouse model. Strains with in vivo inducible protein expression with thePpacCpromoter showed good infection rates and immunogenicity but failed to engender detectable antibodies in the lung. However, a systemic booster vaccination following an oral primary immunization yielded high immunoglobulin A (IgA) and IgG antibody levels in both upper and lower airways superior to conventional systemic or mucosal booster vaccination alone. In addition, the proportion of IgG1 and IgG2a antibodies suggested that the systemic booster does not alter the more TH1-like type of response induced by the oralSalmonellaprimary vaccination. We conclude that an oral primary systemic booster vaccination strategy with an appropriate mucosal vector may be advantageous in diseases with the risk ofP. aeruginosaairway infection, such as cystic fibrosis.
Effect of Dosage on Immunogenicity of a Vi Conjugate Vaccine Injected Twice into 2- to 5-Year-Old Vietnamese Children
Authors: Canh Do Gia , Lin Feng-ying (Kimi) , Thiem Vu Dinh , Trach Dang Duc , Trong Nguyen Dinh , Mao Nguyen Duc , Hunt Steven , Schneerson Rachel , Robbins John B. , Chu Chiayung , Shiloach Joseph , Bryla Dolores A. , Bonnet Marie-Claude , Schulz Dominique , Szu Shousun C. 
Published: October 2004

ABSTRACT

In a double-blind, randomized, and placebo-controlled previous trial, the efficacy of Vi-
r
EPA for typhoid fever in 2- to 5-year-olds was 89.0% for 46 months. Vi-
r
EPA contained 25 μg of Vi and induced a greater-than-eightfold rise in immunoglobulin G (IgG) anti-Vi in all of the vaccinees tested. In this investigation, we conducted a dosage-immunogenicity study of 5, 12.5, and 25 μg of Vi-
r
EPA in this age group. Two doses of Vi-
r
EPA were injected 6 weeks apart. Blood samples were taken before and at 10 weeks (4 weeks after the second injection) and 1 year later. All postimmunization geometric mean (GM) levels were higher than the preimmune levels (
P
< 0.0001). At 10 weeks, the GM IgG anti-Vi level elicited by 25 μg (102 EU/ml) was higher than those elicited by 12.5 μg (74.7 EU/ml) and 5 μg (43 EU/ml) (
P
< 0.004): all of the children had ≥3.52 EU/ml (estimated minimum protective level). One year later, the levels declined about sevenfold (13.3 and 11.3 versus 6.43 EU/ml,
P
< 0.0001) but remained significantly higher than the preimmune levels (
P
< 0.0001), and >96% of the children had a greater-than-eightfold rise. This study also confirmed the safety and consistent immunogenicity of the four lots of Vi-
r
EPA used in this and previous trials.
Quorum Sensing: a Transcriptional Regulatory System Involved in the Pathogenicity of
Burkholderia mallei
Authors: Ulrich Ricky L. , DeShazer David , Hines Harry B. , Jeddeloh Jeffrey A. 
Published: October 2004

ABSTRACT

Numerous gram-negative bacterial pathogens regulate virulence factor expression by using a cell density mechanism termed quorum sensing (QS). An in silico analysis of the
Burkholderia mallei
ATCC 23344 genome revealed that it encodes at least two
luxI
and four
luxR
homologues. Using mass spectrometry, we showed that wild-type
B. mallei
produces the signaling molecules
N
-octanoyl-homoserine lactone and
N
-decanoyl-homoserine lactone. To determine if QS is involved in the virulence of
B. mallei
, we generated mutations in each putative
luxIR
homologue and tested the pathogenicities of the derivative strains in aerosol BALB/c mouse and intraperitoneal hamster models. Disruption of the
B. mallei
QS alleles, especially in RJ16 (
bmaII
) and RJ17 (
bmaI3
), which are
luxI
mutants, significantly reduced virulence, as indicated by the survival of mice who were aerosolized with 10
4
CFU (10 50% lethal doses [LD
50
s]). For the
B. mallei
transcriptional regulator mutants (
luxR
homologues), mutation of the
bmaR5
allele resulted in the most pronounced decrease in virulence, with 100% of the challenged animals surviving a dose of 10 LD
50
s. Using a Syrian hamster intraperitoneal model of infection, we determined the LD
50
s for wild-type
B. mallei
and each QS mutant. An increase in the relative LD
50
was found for RJ16 (
bmaI1
) (>967 CFU), RJ17 (
bmaI3
) (115 CFU), and RJ20 (
bmaR5
) (151 CFU) compared to wild-type
B. mallei
(<13 CFU). These findings demonstrate that
B. mallei
carries multiple
luxIR
homologues that either directly or indirectly regulate the biosynthesis of an essential virulence factor(s) that contributes to the pathogenicity of
B. mallei
in vivo.