bluuebunny/crossref_metadata_2025_split huggingface dataset:
DsrA-Deficient Mutant of
Haemophilus ducreyi
Is Impaired in Its Ability To Infect Human Volunteers
Authors: Bong Cliffton T. H. , Throm Robert E. , Fortney Kate R. , Katz Barry P. , Hood Antoinette F. , Elkins Christopher , Spinola Stanley M. 
Published: July 2002

ABSTRACT

Haemophilus ducreyi
produces an outer membrane protein called DsrA, which is required for serum resistance. An isogenic
dsrA
mutant, FX517, was constructed previously in
H. ducreyi
35000. Compared to its parent, FX517 cannot survive in normal human serum. When complemented
in trans
with a plasmid containing
dsrA
, FX517 is converted to a serum-resistant phenotype (C. Elkins, K. J. Morrow, Jr., and B. Olsen, Infect. Immun. 68:1608–1619, 2000). To test whether
dsrA
was transcribed in vivo, we successfully amplified transcripts in five biopsies obtained from four experimentally infected human subjects. To test whether DsrA was required for virulence, six volunteers were experimentally infected with 35000 and FX517 and observed for papule and pustule formation. Each subject was inoculated with two doses (70 to 80 CFU) of live 35000 and 1 dose of heat-killed bacteria on one arm and with three doses (ranging from 35 to 800 CFU) of live FX517 on the other arm. Papules developed at similar rates at sites inoculated with the mutant or parent. However, mutant papule surface areas were significantly smaller than parent papules. The pustule formation rate was 58% (95% confidence interval [CI] of 28 to 85%) at 12 parent sites, and 0% (95% CI of 0 to 15%) at 18 mutant sites (
P
= 0.0004). Although biosafety regulations precluded our testing the complemented mutant in humans, these results suggest that expression of DsrA facilitates the ability of
H. ducreyi
to progress to the pustular stage of disease.
Streptococcus iniaeVirulence Is Associated with a Distinct Genetic Profile
Authors: Fuller Jeffrey D. , Bast Darrin J. , Nizet Victor , Low Donald E. , de Azavedo Joyce C. S. 
Published: July 2002

ABSTRACTStreptococcus iniaecauses meningoencephalitis and death in commercial fish species and has recently been identified as an emerging human pathogen producing fulminant soft tissue infection. As identified by pulsed-field gel electrophoresis (PFGE), strains causing disease in either fish or humans belong to a single clone, whereas isolates from nondiseased fish are genetically diverse. In this study, we used in vivo and in vitro models to examine the pathogenicity of disease-associated isolates. Strains with the clonal (disease-associated) PFGE profile were found to cause significant weight loss and bacteremia in a mouse model of subcutaneous infection. As little as 102CFU of a disease-associated strain was sufficient to establish bacteremia, with higher inocula (107) resulting in increased mortality. In contrast, non-disease-associated (commensal) strains failed to cause bacteremia and weight loss, even at inocula of 108CFU. In addition, disease-associated strains were more resistant to phagocytic clearance in a human whole blood killing assay compared to commensal strains, which were almost entirely eradicated. Disease-associated strains were also cytotoxic to human endothelial cells as measured by lactate dehydrogenase release from host cells. However, both disease-associated and commensal strains adhered to and invaded cultured human epithelial and endothelial cells equally well. While cellular invasion may still contribute to the pathogenesis of invasiveS. iniaedisease, resistance to phagocytic clearance and direct cytotoxicity appear to be discriminating virulence attributes of the disease-associated clone.
Lack of Expansion of Major Histocompatibility Complex Class Ib-Restricted Effector Cells following Recovery from Secondary Infection with the Intracellular PathogenListeria monocytogenes
Authors: Bouwer H. G. Archie , Barry Ronald A. , Hinrichs David J. 
Published: July 2002

ABSTRACTSublethal infection of BALB/c mice with the intracellular bacterial pathogenListeria monocytogenesleads to the development of antilisterial immunity with concurrent stimulation of major histocompatibility complex (MHC) class Ia- and Ib-restricted CD8+effector T cells. SecondaryL. monocytogenesinfection is followed by an accelerated increase in the number ofListeria-specific CD8+cells and rapid clearance of the bacterium from the murine host. Recovery from secondary infection is associated with increased levels of effector cell function, as measured by gamma interferon secretion following coculture of immune cells withL. monocytogenesinfected APCs in vitro, as well as antilisterial cytotoxicity, as measured by effector cell recognition ofL. monocytogenes-infected target cells. We assessed the frequency ofL. monocytogenes-specific MHC class I-restricted cells following secondary infection by ELISPOT assays utilizing coculture of immune cells withL. monocytogenes-infected antigen-presenting cells that express MHC class Ia and/or Ib molecules. We found that the antilisterial Qa-1b(MHC class Ib)-restricted effector subset is not detected as an expanded population following secondary infection compared to the frequency of this effector population as measured following recovery from primary infection. This is in contrast to the frequency of antilisterial H2-Kd(MHC class Ia)-restricted effector cells, which following recovery from secondary infection are detected as an expanded population, and appears to undergo a substantial expansion event 3 to 4 days post-secondary infection. These results are consistent with the conclusion that althoughListeria-specific MHC class Ib-restricted effector cells are present following recovery from secondary infection, this subset does not appear to undergo the expansion phase that is detected for the MHC class Ia-restricted effector cell response.
Antigastric Autoantibodies in Ferrets Naturally Infected with
Helicobacter mustelae
Authors: Cróinı́n Tadhg Ó , Clyne Marguerite , Appelmelk Ben J. , Drumm Brendan 
Published: July 2002

ABSTRACT

Infection with
Helicobacter pylori
has been associated with induction of autoantibodies that cross-react with the gastric mucosa. There have been discordant reports as to whether or not these autoantibodies arise due to molecular mimicry between
H. pylori
and host cell antigens on parietal cells. In this study, we investigated whether molecular mimicry by
H. mustelae
causes autoantibodies in infected ferrets. Serum from
H. mustelae
-infected ferrets reacted with parietal cells in the ferret gastric mucosa but not with duodenal or colonic mucosa. These sera did not react with the blood group A epitope on erythrocytes or
H. mustelae
lipopolysaccharide, and absorption with
H. mustelae
whole cells or red blood cells did not remove autoantibodies. In conclusion, ferrets naturally infected with
H. mustelae
generate antibodies that react with parietal cells, but these autoantibodies are not due to molecular mimicry.
Induction of Systemic Antifimbria and Antitoxin Antibody Responses in Egyptian Children and Adults by an Oral, Killed Enterotoxigenic
Escherichia coli
plus Cholera Toxin B Subunit Vaccine
Authors: Hall Eric R. , Wierzba Thomas F. , Åhrén Christina , Rao Malla R. , Bassily Samir , Francis Wagdy , Girgis Fouad Y. , Safwat Mohamed , Lee Young J. , Svennerholm Ann-Mari , Clemens John D. , Savarino Stephen J. 
Published: July 2002

ABSTRACT

We assessed serologic responses to an oral, killed whole-cell enterotoxigenic
Escherichia coli
plus cholera toxin B-subunit (ETEC-rCTB) vaccine in 73 Egyptian adults, 105 schoolchildren, and 93 preschool children. Each subject received two doses of vaccine or placebo 2 weeks apart, giving blood before immunization and 7 days after each dose. Plasma antibodies to rCTB and four vaccine-shared colonization factors (CFs) were measured by enzyme-linked immunosorbent assay. Immunoglobulin A (IgA) antibodies to rCTB and CFA/I were measured in all subjects, and those against CS1, CS2, and CS4 were measured in all children plus a subset of 33 adults. IgG antibodies to these five antigens were measured in a subset of 30 to 33 subjects in each cohort. Seroconversion was defined as a >2-fold increase in titer after vaccination. IgA and IgG seroconversion to rCTB was observed in 94 to 95% of adult vaccinees, with titer increases as robust as those previously reported for these two pediatric cohorts. The proportion showing IgA seroconversion to each CF antigen among vaccinated children (range, 70 to 96%) and adults (31 to 69%), as well as IgG seroconversion in children (44 to 75%) and adults (25 to 81%), was significantly higher than the corresponding proportion in placebo recipients, except for IgA responses to CS2 in adults. IgA anti-CF titers peaked after one dose in children, whereas in all age groups IgG antibodies rose incrementally after each dose. Independently, both preimmunization IgA titer and age were inversely related to the magnitude of IgA responses. In conclusion, serologic responses to the ETEC-rCTB vaccine may serve as practical immune outcome measures in future pediatric trials in areas where ETEC is endemic.
Characterization of Proteins in the Outer Membrane Preparation of a Murine Pathogen,
Helicobacter bilis
Authors: Ge Zhongming , Doig Peter , Fox James G. 
Published: July 2002

ABSTRACT

Helicobacter bilis
is a bacterial pathogen associated with multifocal hepatitis and inflammatory bowel disease in certain strains of mice. This bacterium colonizes the liver, bile, and lower intestine in mice and has also been isolated from a wide spectrum of laboratory animals. In this study, proteins present in the outer membrane preparation (OMP) of four
H. bilis
strains isolated from a mouse, a dog, a rat, and a gerbil were characterized and compared with that of
Helicobacter pylori
, a human gastric pathogen. All four
H. bilis
strains had similar OMP protein profiles that were distinct from those of
H. pylori
. Immunoblotting demonstrated that OMP proteins from
H. bilis
and
H. pylori
have little cross-reactivity, except for their flagellins. Nine major immunogenic polypeptides were present in the
H. bilis
OMPs. By using two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis, five heat-modifiable proteins with molecular masses of 82, 66, 52, 47 and 37 kDa were identified. The N-terminal sequences of the 46- and 47-kDa OMP proteins had no homology with protein sequences available in public databases. These results indicate that
H. bilis
has a conserved, unique OMP protein profile that is distinct from those of
H. pylori
.
Identification of a Novel T-Cell Epitope in Soluble Egg Antigen ofSchistosoma japonicum
Authors: Liu Jie , Tasaka Kachio , Yang Junqi , Itoh Takehito , Yamada Muneo , Yoshikawa Hideshi , Nakajima Yasuo 
Published: July 2002

ABSTRACTIdentification of T-cell epitopes harbored in soluble egg antigen (SEA) ofSchistosoma japonicumand study of the immunological properties are essential for understanding the immunopathology and the control of schistosomiasis. As a follow-up to our previous work, the 66- to 80-kDa fragment from SEA was partially digested with protease, fractionated by reverse-phase high-pressure liquid chromatography, and found to be carrying a peptide which stimulated proliferation and gamma interferon (IFN-γ) production of Th1 clones specific to SEA. Sequence analysis showed that the peptide was composed of 12 amino acids lined up as DLAVELAYLGNL. A synthetic homologue induced proliferation and IFN-γ and interleukin-2 (IL-2) production, but not IL-4 or IL-6 production, by the Th1 clones as well as by the spleen cells from SEA-immunized mice, thus indicating that the peptide carries a Th1 epitope of SEA.
S-Fimbria-Encoding Determinant
sfa
I
Is Located on Pathogenicity Island III
536
of Uropathogenic
Escherichia coli
Strain 536
Authors: Dobrindt Ulrich , Blum-Oehler Gabriele , Hartsch Thomas , Gottschalk Gerhard , Ron Eliora Z. , Fünfstück Reinhard , Hacker Jörg 
Published: July 2002

ABSTRACT

The
sfa
I
determinant encoding the S-fimbrial adhesin of uropathogenic
Escherichia coli
strains was found to be located on a pathogenicity island of uropathogenic
E. coli
strain 536. This pathogenicity island, designated PAI III
536
, is located at 5.6 min of the
E. coli
chromosome and covers a region of at least 37 kb between the tRNA locus
thrW
and
yagU
. As far as it has been determined, PAI III
536
also contains genes which code for components of a putative enterochelin siderophore system of
E. coli
and
Salmonella
spp. as well as for colicin V immunity. Several intact or nonfunctional mobility genes of bacteriophages and insertion sequence elements such as transposases and integrases are present on PAI III
536
. The presence of known PAI III
536
sequences has been investigated in several wild-type
E. coli
isolates. The results demonstrate that the determinants of the members of the S-family of fimbrial adhesins may be located on a common pathogenicity island which, in
E. coli
strain 536, replaces a 40-kb DNA region which represents an
E. coli
K-12-specific genomic island.
Towards Development of an Edible Vaccine against Bovine Pneumonic Pasteurellosis Using Transgenic White Clover Expressing aMannheimia haemolyticaA1 Leukotoxin 50 Fusion Protein
Authors: Lee Raymond W. H. , Strommer Judith , Hodgins Doug , Shewen Patricia E. , Niu Yongqing , Lo Reggie Y. C. 
Published: July 2002

ABSTRACTDevelopment of vaccines against bovine pneumonia pasteurellosis, or shipping fever, has focused mainly onMannheimia haemolyticaA1 leukotoxin (Lkt). In this study, the feasibility of expressing Lkt in a forage plant for use as an edible vaccine was investigated. Derivatives of theM. haemolyticaLkt in which the hydrophobic transmembrane domains were removed were made. Lkt66 retained its immunogenicity and was capable of eliciting an antibody response in rabbits that recognized and neutralized authentic Lkt. Genes encoding a shorter Lkt derivative, Lkt50, fused to a modified green fluorescent protein (mGFP5), were constructed for plant transformation. Constructs were screened by Western immunoblot analysis for their ability to express the fusion protein after agroinfiltration in tobacco. The fusion construct pBlkt50-mgfp5, which employs the cauliflower mosaic virus 35S promoter for transcription, was selected and introduced into white clover byAgrobacterium tumefaciens-mediated transformation. Transgenic lines of white clover were recovered, and expression of Lkt50-GFP was monitored and confirmed by laser confocal microscopy and Western immunoblot analysis. Lkt50-GFP was found to be stable in clover tissue after drying of the plant material at room temperature for 4 days. An extract containing Lkt50-GFP from white clover was able to induce an immune response in rabbits (via injection), and rabbit antisera recognized and neutralized authentic Lkt. This is the first demonstration of the expression of anM. haemolyticaantigen in plants and paves the way for the development of transgenic plants expressingM. haemolyticaantigens as an edible vaccine against bovine pneumonic pasteurellosis.
Bacterial Lipoprotein-Based Vaccines Induce Tumor Necrosis Factor-Dependent Type 1 Protective Immunity againstLeishmania major
Authors: Cote-Sierra Javier , Bredan Amin , Toldos Carmen M. , Stijlemans Benoit , Brys Lea , Cornelis Pierre , Segovia Manuel , de Baetselier Patrick , Revets Hilde 
Published: July 2002

ABSTRACTImmunity againstLeishmania majorrequires rapid induction of a type 1 immune response in which tumor necrosis factor alpha (TNF-α) plays an essential role. Hence, vaccination strategies that simulate the protective immune response found in hosts that have recovered from natural infection provide a rational approach to combat leishmaniasis. One method for optimizing the qualitative and quantitative immune responses after vaccination is to use an adjuvant. In this study we demonstrate that the OprI lipoprotein (L-OprI) fromPseudomonas aeruginosainduces a long-term cellular (gamma interferon [IFN-γ]) and humoral (immunoglobulin G2a) type 1 immune response against a truncated 32-kDa version (COOHgp63) of the 63-kDa major cell surface glycoprotein gp63. By contrast, immunization with COOHgp63 either fused to OprI nonlipoprotein or with no adjuvant did not result in the induction of type 1 immune responses. The adjuvanticity of L-OprI is strongly dependent on its capacity to induce TNF-α, since generation of type 1 immune responses is clearly delayed and impaired in TNF-α−/−mice. Vaccination with L-OprICOOHgp63 fusion protein protected BALB/c mice againstL. majorinfection for at least 19 weeks. Vaccinated mice were largely free of lesions or clearly controlled lesion size on termination of the experiment. The control of disease progression in mice vaccinated with L-OprICOOHgp63 was associated with enhancement of antigen-specific IFN-γ production. These data indicate that bacterial lipoproteins constitute appropriate adjuvants to include in vaccines against diseases in which type 1 immune responses are important for protection.
Molecular Analysis of Group B Protective Surface Protein, a New Cell Surface Protective Antigen of Group B Streptococci
Authors: Erdogan Sezgin , Fagan Peter K. , Talay Susanne R. , Rohde Manfred , Ferrieri Patricia , Flores Aurea E. , Guzmán Carlos A. , Walker Mark J. , Chhatwal Gursharan S. 
Published: July 2002

ABSTRACT

Group B streptococci (GBS) express various surface antigens designated c, R, and X antigens. A new R-like surface protein from
Streptococcus agalactiae
strain Compton R has been identified by using a polyclonal antiserum raised against the R protein fraction of this strain to screen a lambda Zap library. DNA sequence analysis of positive clones allowed the prediction of the primary structure of a 105-kDa protein designated BPS protein (group B protective surface protein) that exhibited typical features of streptococcal surface proteins such as a signal sequence and a membrane anchor region but did not show significant similarity with other known sequences. Immunogold electron microscopy using a BPS-specific antiserum confirmed the surface location of BPS protein on
S. agalactiae
strain Compton R. Anti-BPS antibodies did not cross-react with R1 and R4 proteins expressed by two variant type III GBS strains but reacted with the parental streptococcal strain in Western blot and immunoprecipitation analyses. Separate R3 and BPS immunoprecipitation bands were observed when a cell extract of strain Compton R was tested with an antiserum against Compton R previously cross-absorbed to remove R4 antibodies. Immunization of mice with recombinant BPS protein by the subcutaneous route produced an efficient antigen-specific response, and immunized animals survived challenge with a lethal dose of a virulent strain. Therefore, BPS protein represents a new R-like protective antigen of GBS.
Cross-Protective Immunity of Mice Induced by Oral Immunization with Pneumococcal Surface Adhesin A Encapsulated in Microspheres
Authors: Seo Jun-Young , Seong Seung Yong , Ahn Byung-Yoon , Kwon Ick Chan , Chung Hesson , Jeong Seo Young 
Published: July 2002

ABSTRACTThe global use of a capsular polysaccharide-based pneumococcal vaccine has been limited because of serotype-specific protection and poor effectiveness in individuals with low immunocompetency. The mucosal immune system develops earlier in infants and lasts longer in the elderly than does the systemic immune system. Furthermore, mucosal immunization is beneficial for AIDS patients, because human immunodeficiency virus-infected subjects can develop normal mucosal antibody responses even in late clinical phases. For these reasons, we evaluated recombinant pneumococcal surface adhesin A (rPsaA) ofStreptococcus pneumoniaein terms of cross-protective immune responses after oral delivery. Encapsulated rPsaA provided higher immunogenicity than naked rPsaA. Coencapsulation or codelivery of the cholera toxin (CT) B subunit (CTB) and CT also increased the immunogenicity of rPsaA. Cross-protective immunities against five strains ofS. pneumoniae(types 4, 6B, 14, 19F, and 23F) were induced after oral immunization with microencapsulated rPsaA. Lung colonization and septicemia caused by the five serotypes were significantly inhibited by oral immunization with microencapsulated rPsaA. These results suggest that rPsaA coencapsulated with CTB can be used as an oral vaccine to induce cross-protective immunity for the prevention of pneumococcal infection.
Increased Interleukin 4 (IL-4) Receptor Expression and IL-4-Induced Decrease in IL-12 Production by Langerhans Cells Infected withLeishmania major
Authors: Moll Heidrun , Scharner Anabel , Kämpgen Eckhart 
Published: July 2002

ABSTRACTLangerhans cells (LC) take upLeishmania majorand are critical for the induction of the parasite-specific T-cell response. Their functional activities are regulated by cytokines. We analyzed whether infection of LC withL. majormodulates the expression of their cytokine receptors. The expression of the interleukin 4 (IL-4) receptor was increased on infected LC from susceptible mice but not on those from resistant mice. Moreover, IL-4 treatment strongly decreased the lipopolysaccharide-induced IL-12 response of infected LC from susceptible mice. This modulation of IL-4 receptor expression and IL-12 production by infection of LC withLeishmaniamay contribute to the development of Th2 cells and to susceptibility to infection.
The Major Structural Subunits of Dr and F1845 Fimbriae Are Adhesins
Authors: Van Loy Cristina P. , Sokurenko Evgeni V. , Moseley Steve L. 
Published: July 2002

ABSTRACT

Fimbrial adhesins mediate the attachment of pathogenic
Escherichia coli
to various host tissues leading to the development of disease. The Dr hemagglutinin and F1845 fimbriae belong to the Dr family of adhesins, which is associated with urinary tract infections and diarrheal disease. These adhesins bind to the Dr
a
blood-group antigen present on decay-accelerating factor (DAF). The Dr hemagglutinin is unique in this family since it also binds to type IV collagen and its binding is inhibited by the presence of chloramphenicol. We have purified the major structural subunits of Dr and F1845 fimbriae, DraE and DaaE, as fusions to maltose-binding protein and to oligohistidine tags and examined their binding to erythrocytes, Chinese hamster ovary cell transfectants expressing DAF, and a DAF fusion protein. The DraE and DaaE fusion proteins bind to the DAF receptor in a specific manner resembling the distinct phenotypes of the corresponding Dr and F1845 fimbriae. In contrast to binding studies with the DAF receptor, the DraE fusion proteins did not bind to type IV collagen.