bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pneumococcal Behavior and Host Responses during Bronchopneumonia Are Affected Differently by the Cytolytic and Complement-Activating Activities of Pneumolysin
Authors: Jounblat Rania , Kadioglu Aras , Mitchell Tim J. , Andrew Peter W. 
Published: March 2003

ABSTRACT

Pneumolysin, a multifunctional toxin produced by all clinical isolates of
Streptococcus pneumoniae
, is strongly implicated in the pathogenesis of pneumococcal bronchopneumonia and septicemia. Using isogenic mutant strains, we examined the effect of deletion of the cytotoxic activity or complement-activating activity of pneumolysin on bacterial growth in lungs and blood, histological changes in infected lung tissue, and the pattern of inflammatory cell recruitment. Both of the activities of pneumolysin contributed to the pathology in the lungs, as well as the timing of the onset of bacteremia. Histological changes in the lungs were delayed after infection with either mutant compared to the changes seen after infection with the wild-type pneumococcus. The complement-activating activity of pneumolysin affected the accumulation of T cells, whereas the toxin's cytolytic activity influenced neutrophil recruitment into lung tissue.
Protective Efficacy of Anti-HelicobacterpyloriImmunity following Systemic Immunization of Neonatal Mice
Authors: Eisenberg Julia C. , Czinn Steven J. , Garhart Christine A. , Redline Raymond W. , Bartholomae Wolf C. , Gottwein Judith M. , Nedrud John G. , Emancipator Steven E. , Boehm Bernhard B. , Lehmann Paul V. , Blanchard Thomas G. 
Published: March 2003

ABSTRACTHelicobacterpyloriinfection of the gastric mucosa is a significant cause of morbidity and mortality because of its etiologic role in symptomatic gastritis, peptic ulcer disease, and gastric adenocarcinoma. Infection occurs in young children; therefore, a prophylactic vaccine would have to be administered within the first year of life, a period thought to be immunologically privileged. We investigated vaccine formulations administered by different routes to confer protective anti-H.pyloriimmunity in neonatal mice. Neonatal mice immunized with a single dose of vaccine in complete Freund's adjuvant (CFA) generated antigen-specific gamma interferon-, interleukin-2 (IL-2)-, IL-4-, and IL-5-secreting T cells in numbers similar to those in immunized adult mice, while vaccine administered to neonates in incomplete Freund's adjuvant (IFA) induced such cells in reduced numbers compared to those in adult mice. Both IFA and CFA, however, provided partial protection from a challenge with infectiousH. pyloriwhen the vaccine was administered subcutaneously. Neonatal immunized mice also had reduced bacterial loads when immunized intraperitoneally with CFA. In all cases, protection was equivalent to that achieved when adult counterparts were immunized. These studies suggest that an efficacious vaccine might be successfully administered to very young children to prevent perinatal infection ofH.pylori.
Characterization of
Cryptosporidium meleagridis
of Human Origin Passaged through Different Host Species
Authors: Akiyoshi Donna E. , Dilo Julia , Pearson Christine , Chapman Susan , Tumwine James , Tzipori Saul 
Published: March 2003

ABSTRACT

Cryptosporidium meleagridis
, a protozoon first observed in turkeys, has been linked by several investigators to cryptosporidiosis in humans.
C. meleagridis
is the only known
Cryptosporidium
species that infects both avian and mammalian species. We describe the successful propagation of
C. meleagridis
(isolate TU1867), originally purified from a patient with diarrhea, in laboratory animals including chickens, mice, piglets, and calves. TU1867 was readily transmitted from one animal host to another, maintaining genetic homogeneity and stability. The rate of infectivity and virulence of TU1867 for the mammalian species were similar to those of
Cryptosporidium parvum
. Laboratory propagation of genetically and phenotypically stable and well-characterized reference isolates, representing various
Cryptosporidium
species, particularly those infectious to humans, will improve considerably the spectrum and quality of laboratory and field investigations on this medically important protozoa.
Repeat Sequences in Block 2 ofPlasmodium falciparumMerozoite Surface Protein 1 Are Targets of Antibodies Associated with Protection from Malaria
Authors: Polley Spencer D. , Tetteh Kevin K. A. , Cavanagh David R. , Pearce Richard J. , Lloyd Jennifer M. , Bojang Kalifa A. , Okenu Daniel M. N. , Greenwood Brian M. , McBride Jana S. , Conway David J. 
Published: March 2003

ABSTRACTHuman antibodies to the block 2 region ofPlasmodium falciparummerozoite surface protein 1 (MSP1) are associated with a reduced prospective risk of clinical malaria. Block 2 is highly polymorphic, but all known alleles can be grouped into three major types. Two of these types (the K1-like and MAD20-like types) contain type-specific sequences (found in all alleles of a particular type) that flank polymorphic tripeptide repeats. These repeats contain both type-specific and subtype-specific sequences. To evaluate the antibody recognition of these parts of block 2, a new panel of six recombinant proteins was used (fused type-specific flanking sequences and two representative repeat sequences for each of the K1-like and MAD20-like types separately). Extensive testing of these antigens and full-length block 2 antigens showed that human serum immunoglobulin G antibodies induced by infection can recognize (i) type-specific epitopes in the repeats, (ii) subtype-specific epitopes in the repeats, or (iii) type-specific epitopes in flanking sequences. A large prospective study in The Gambia showed that antibodies to the repeats are strongly associated with protection from clinical malaria. The results are important for design of a vaccine to induce protective antibodies, and they address hypotheses about repeat sequences in malaria antigens.
Inactivation of the
Moraxella catarrhalis
7169 Ferric Uptake Regulator Increases Susceptibility to the Bactericidal Activity of Normal Human Sera
Authors: Furano Kristin , Campagnari Anthony A. 
Published: March 2003

ABSTRACT

Moraxella catarrhalis
is a strict human pathogen and a significant cause of respiratory disease and otitis media. In direct response to these infections, research efforts have focused primarily on the identification of potential vaccine targets. The general biology of
M. catarrhalis
, however, including the mechanisms utilized to survive in the human host, remains poorly understood. Previous work has demonstrated that
M. catarrhalis
expresses iron-repressible proteins, suggesting the presence of iron acquisition systems under the control of a ferric uptake regulator (Fur). In this study
M. catarrhalis fur
has been cloned and sequenced from strain 7169. A deletion-insertion mutation of 7169
fur
resulted in upregulation of iron-repressible outer membrane proteins in the absence and presence of iron. This mutant strain, 7169
fur
1, was significantly more sensitive to the bactericidal activity of normal human serum than the resistant wild-type strain. These data suggest that constitutive expression of iron-regulated proteins may provide multiple targets for human antibodies. In addition, the 7169
fur
mutant provides an important tool for further investigation of the iron acquisition mechanisms utilized by
M. catarrhalis
.
Development and Evaluation of an Improved Mouse Model of Meningococcal Colonization
Authors: Yi Kyungcheol , Stephens David S. , Stojiljkovic Igor 
Published: March 2003

ABSTRACTStudies of meningococcal pathogenesis have been severely restricted due to the absence of an adequate animal model. Given the significance of iron in meningococcal pathogenesis, we developed a model ofNeisseria meningitidiscolonization in outbred adult mice that included daily administration of iron dextran. While receiving iron, the animals were inoculated intranasally with the initial doses of bacterial suspension. Meningococci were recovered from the animals by nasopharyngeal washes. Approximately half of the animals inoculated with 107CFU remained colonized 13 days after the initial bacterial inoculation. The model was further evaluated with genetically defined isogenic serogroup B mutant strains, and the colonization capabilities of the mutants were compared to that of the wild-type parent. A mutant that produces truncated lipooligosaccharide (KDO2-lipid A) and a mutant defective in capsule transport were dramatically impaired in colonization. A mutant defective in pilus transport (pilQ) showed moderately impaired colonization. The immunological aspect of the model was also evaluated by challenging mice after immunization with homologous whole-cell meningococci. The immunized mice were protected from colonization of the homologous strain. In this model, long-term meningococcal colonization was maintained, allowing us to study the effects of specific genetic mutation on colonization. In addition, this model allows investigation of the role of active immune response against meningococci.
Erythrocyte Invasion Phenotypes of
Plasmodium
falciparum
in The Gambia
Authors: Baum Jake , Pinder Margaret , Conway David J. 
Published: March 2003

ABSTRACT

In vitro experimentation with
Plasmodium
falciparum
has determined that a number of different receptor-ligand interactions are involved in the invasion of erythrocytes. Most culture-adapted parasite isolates use a mechanism of invasion that depends primarily on the erythrocyte sialoglycoprotein glycophorin A (GYPA) and erythrocyte-binding antigen 175 (EBA-175) of the parasite blood-stage merozoite. However, a minority of culture-adapted parasites and a majority of Indian field isolates can apparently invade by other means. Here, erythrocyte invasion phenotypes of
P
.
falciparum
field isolates in Africa were studied. For 38 Gambian isolates, invasion of neuraminidase-treated and trypsin-treated erythrocytes was inhibited, on average, by more than 60 and 85%, respectively, indicating a high level of dependence on sialic acid and trypsin-sensitive proteins on the erythrocyte surface. These results support the hypothesis that African
P
.
falciparum
parasites use GYPA as a primary receptor for invasion. However, the considerable variation among isolates confirms the idea that alternative receptors are also used by many parasites. Three amino acid polymorphisms in the GYPA-binding region of EBA-175 (region II) were not significantly associated with invasion phenotype. There was variation among isolates in the selectivity index (i.e., a statistical tendency toward aggregation or multiple invasions of host erythrocytes), but this variation did not correlate with enzyme-determined invasion phenotype or with
eba-175
alleles. Overall, these invasion phenotypes in Africa support a vaccine strategy of inhibiting EBA-175 binding to GYPA but suggest that parasites with alternative phenotypes would be selected for if this strategy were used alone.
Role of Glutathione in Macrophage Control of Mycobacteria
Authors: Venketaraman Vishwanath , Dayaram Yaswant K. , Amin Amol G. , Ngo Richard , Green Renee M. , Talaue Meliza T. , Mann Jessica , Connell Nancy D. 
Published: March 2003

ABSTRACTReactive oxygen and nitrogen intermediates are important antimicrobial defense mechanisms of macrophages and other phagocytic cells. While reactive nitrogen intermediates have been shown to play an important role in tuberculosis control in the murine system, their role in human disease is not clearly established. Glutathione, a tripeptide and antioxidant, is synthesized at high levels by cells during reactive oxygen intermediate and nitrogen intermediate production. Glutathione has been recently shown to play an important role in apoptosis and to regulate antigen-presenting-cell functions. Glutathione also serves as a carrier molecule for nitric oxide, in the form ofS-nitrosoglutathione. Previous work from this laboratory has shown that glutathione andS-nitrosoglutathione are directly toxic to mycobacteria. A mutant strain ofMycobacterium bovisBCG, defective in the transport of small peptides such as glutathione, is resistant to the toxic effect of glutathione andS-nitrosoglutathione. Using the peptide transport mutant as a tool, we investigated the role of glutathione andS-nitrosoglutathione in animal and human macrophages in controlling intracellular mycobacterial growth.
Novel Virulence-Associated Type II Secretion System Unique to High-PathogenicityYersinia enterocolitica
Authors: Iwobi A. , Heesemann J. , Garcia E. , Igwe E. , Noelting C. , Rakin A. 
Published: March 2003

ABSTRACTYersinia enterocoliticastrains comprise an important group of bacterial enteropathogens that cause a broad range of gastrointestinal syndromes. Three groups are distinguishable within this bacterial species, namely, the nonpathogenic group (biotype 1A strains), the low-pathogenicity, non-mouse-lethal group (biotypes 2 to 5), and the high-pathogenicity, mouse-lethal group (biotype 1B). To date, the presence of the high-pathogenicity island (HPI), a chromosomal locus that encodes the yersiniabactin system (involved in iron uptake), defines essentially the difference between low-pathogenicity and high-pathogenicityY. enterocoliticastrains, with the low-pathogenicity strains lacking the HPI. Using the powerful tool of representational difference analysis between the nonpathogenic 1A strain, NF-O, and its high-pathogenicity 1B counterpart, WA-314, we have identified a novel type II secretion gene cluster (yts1C-S) occurring exclusively in the high-pathogenicity group. The encoded secreton, designated Yts1 (forYersiniatype II secretion 1) was shown to be important for virulence in mice. A close examination of the almost completed genome sequence of another high-pathogenicity representative,Y. enterocolitica8081, revealed a second putative type II secretion cluster uniformly distributed among allY. enterocoliticaisolates. This putative species-specific cluster (designatedyts2) differed significantly fromyts1, while resembling more closely the putative type II cluster present on the genome ofY. pestis. The Yts1 secreton thus appears to have been additionally acquired by the high-pathogenicity assemblage for a virulence-associated function.
Oral Transfer of Adult
Ancylostoma ceylanicum
Hookworms into Permissive and Nonpermissive Host Species
Authors: Bungiro Richard D. , Anderson Brett R. , Cappello Michael 
Published: March 2003

ABSTRACT

Syrian hamsters become anemic and exhibit delayed growth following oral infection with third-stage
Ancylostoma ceylanicum
hookworm larvae. Here we describe experiments designed to determine the feasibility of adult worm transfer (AWT) between hosts, a technique that would facilitate the specific study of bloodfeeding hookworms in vivo without prior exposure of the host to larva-specific antigens, permit the ex vivo manipulation of adult parasites prior to reimplantation, and also allow for cross-species transfer of worms. Weanling hamsters given an oral AWT of 40 or 60 mixed-sex
A. ceylanicum
worms rapidly developed anemia; in the higher-dose group, hemoglobin levels declined from prechallenge levels by 44% within 4 days following AWT. Long-term survival of transferred worms was demonstrated by recovery of parasites from the intestines 42 days after AWT. AWT hamsters acquired humoral immune responses against soluble adult hookworm extracts and excretory-secretory products that were comparable in magnitude to those of animals given a typical infection with larvae. In AWT experiments employing the nonpermissive murine model, C57BL/6 mice given adult worms rapidly became anemic and lost weight in a manner similar to AWT hamsters. Infection of additional mouse strains demonstrated that while C57BL/10 and CD-1 mice also developed anemia following AWT, BALB/c mice were resistant. The technique of AWT to mice may further our understanding of hookworm pathogenesis by allowing the study of adult hookworm infections in a species with well-characterized genetics and an abundance of available reagents.
Intranasal Immunization with RecombinantLactococcus lactisSecreting Murine Interleukin-12 Enhances Antigen-Specific Th1 Cytokine Production
Authors: Bermúdez-Humarán Luis G. , Langella Philippe , Cortes-Perez Naima G. , Gruss Alexandra , Tamez-Guerra Reyes S. , Oliveira Sergio C. , Cardenas Odila Saucedo- , Montes de Oca-Luna Roberto , Le Loir Yves 
Published: March 2003

ABSTRACTInterleukin-12 (IL-12), a heterodimeric cytokine, plays an important role in cellular immunity to several bacterial, viral, and parasitic infections and has adjuvant activity when it is codelivered with DNA vaccines. IL-12 has also been used with success in cancer immunotherapy treatments. However, systemic IL-12 therapy has been limited by high levels of toxicity. We describe here inducible expression and secretion of IL-12 in the food-grade lactic acid bacteriumLactococcus lactis.IL-12 was expressed as two separate polypeptides (p35-p40) or as a single recombinant polypeptide (scIL-12). The biological activity of IL-12 produced by the recombinantL. lactisstrain was confirmed in vitro by its ability to induce gamma interferon (IFN-γ) production by mouse splenocytes. Local administration of IL-12-producing strains at the intranasal mucosal surface resulted in IFN-γ production in mice. The activity was greater with the single polypeptide scIL-12. An antigen-specific cellular response (i.e., secretion of Th1 cytokines, IL-2, and IFN-γ) elicited by a recombinantL. lactisstrain displaying a cell wall-anchored human papillomavirus type 16 E7 antigen was dramatically increased by coadministration with anL. lactisstrain secreting IL-12 protein. Our data show that IL-12 is produced and secreted in an active form byL. lactisand that the strategy which we describe can be used to enhance an antigen-specific immune response and to stimulate local mucosal immunity.
Zonula Occludens Toxin Acts as an Adjuvant through Different Mucosal Routes and Induces Protective Immune Responses
Authors: Marinaro Mariarosaria , Fasano Alessio , De Magistris Maria Teresa 
Published: March 2003

ABSTRACTZonula occludens toxin (Zot) is produced byVibrio choleraeand has the ability to increase mucosal permeability by reversibly affecting the structure of tight junctions. Because of this property, Zot is a promising tool for mucosal drug and antigen (Ag) delivery. Here we show that Zot acts as a mucosal adjuvant to induce long-lasting and protective immune responses upon mucosal immunization of mice. Indeed, the intranasal delivery of ovalbumin with two different recombinant forms of Zot in BALB/c mice resulted in high Ag-specific serum immunoglobulin G titers that were maintained over the course of a year. Moreover, His-Zot induced humoral and cell-mediated responses to tetanus toxoid in C57BL/6 mice and protected the mice against a systemic challenge with tetanus toxin. In addition, we found that Zot also acts as an adjuvant through the intrarectal route and that it has very low immunogenicity compared to the adjuvantEscherichia coliheat-labile enterotoxin. Finally, by using an octapeptide representing the putative binding site of Zot and of its endogenous analogue zonulin, we provide evidence that Zot may bind a mucosal receptor on nasal mucosa and may mimic an endogenous regulator of tight junctions to deliver Ags in the submucosa. In conclusion, Zot is a novel and effective mucosal adjuvant that may be useful for the development of mucosal vaccines.
M Type 1 and 3 Group A Streptococci Stimulate Tissue Factor-Mediated Procoagulant Activity in Human Monocytes and Endothelial Cells
Authors: Bryant A. E. , Hayes-Schroer S. M. , Stevens D. L. 
Published: March 2003

ABSTRACTStreptococcal toxic shock syndrome (StrepTSS) is an invasive infection characterized by marked coagulopathy, multiple organ failure, and rapid tissue destruction and is strongly associated with M type 1 and 3 group A streptococci (GAS). Initiation of the coagulation cascade with formation of microvascular thrombi contributes to multiple organ failure in human cases of gram-negative bacteremia; however, little is known regarding the mechanism of coagulopathy in StrepTSS. Thus, we investigated the abilities of several strains of M type 1 and 3 GAS isolated from human cases of StrepTSS to stimulate production of tissue factor (TF), the principal initiator of coagulation in vivo. Washed, killed M type 1 and 3 GAS, but not M type 6 GAS, elicited high-level TF-mediated procoagulant activity from both isolated human monocytes and cultured human umbilical vein endothelial cells. M type 1 GAS consistently elicited higher levels of TF from monocytes than did M type 3 GAS. GAS-induced TF synthesis in monocytes did not correlate with production of tumor necrosis factor alpha or interleukin-8. Conversely, M type 3 GAS were consistently more potent than M type 1 GAS in stimulating endothelial cell TF synthesis. These results demonstrate that (i) M type 1 and 3 strains of GAS are potent inducers of TF synthesis, (ii) GAS-induced TF synthesis is not simply an epiphenomenon of cytokine generation, and (iii) induction of TF in endothelial cells and monocytes may be M type specific. In total, these findings suggest that a novel interaction between GAS and host cells contributes to the observed coagulopathy in StrepTSS.
P-Selectin Contributes to Severe Experimental Malaria but Is Not Required for Leukocyte Adhesion to Brain Microvasculature
Authors: Chang Wun-Ling , Li Jie , Sun Guang , Chen Hong-Li , Specian Robert D. , Berney Seth Mark , Granger D. Neil , van der Heyde Henri C. 
Published: March 2003

ABSTRACTPlasmodium berghei-infected mice, a well-recognized model of experimental cerebral malaria (ECM), exhibit many of the hallmarks of a systemic inflammatory response, with organ damage in brain, lung, and kidneys. Identification of the molecules mediating pathogenesis of the inflammatory response, such as leukocyte adhesion, may lead to new therapies. Indeed, mice lacking the cell adhesion molecule P-selectin were significantly (P= 0.005) protected from death due toP. bergheimalaria compared with C57BL/6 controls despite similar parasitemia (P= 0.6) being found in both groups of mice. P-selectin levels assessed by the quantitative dual radiolabeled monoclonal antibody technique increased significantly (P< 0.05) in several organs in C57BL/6 mice infected withP. berghei, supporting the concept of a systemic inflammatory response mediating malarial pathogenesis. Intravital microscopic analysis of the brain microvasculature demonstrated significant (P< 0.001) leukocyte rolling and adhesion in brain venules ofP. berghei-infected mice compared with those found in uninfected controls. The maximum leukocyte adhesion occurred on day 6 ofP. bergheiinfection, when the mice become moribund and exhibit marked vascular leakage into the brain, lung, and heart. However, P-selectin levels were significantly (P< 0.005) increased in brain, lung, and kidneys duringP. bergheimalaria in ECM-resistant BALB/c mice compared with those found in uninfected BALB/c controls, indicating that increased P-selectin alone is not sufficient to mediate malarial pathogenesis. Leukocyte adhesion to brain microvessels of P-selectin-deficient mice withP. bergheimalaria was similar to that observed in control mice. Collectively, these results indicate that P-selectin is important for the development of malarial pathogenesis but is not required for leukocyte adhesion in brain.