bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thioredoxin fromBrugia malayi:Defining a 16-Kilodalton Class of Thioredoxins from Nematodes
Authors: Kunchithapautham Kannan , Padmavathi B. , Narayanan R. B. , Kaliraj P. , Scott Alan L. 
Published: June 2003

ABSTRACTThioredoxins are a family of small redox proteins that undergo NADPH-dependent reduction by thioredoxin reductase. This results in a supply of reducing equivalents that cells use in a wide variety of biological reactions, which include maintaining reduced forms of the enzymes important for protection against damage from high-energy oxygen radicals, the regulation of transcription factor activity, and the inhibition of apoptosis. Here we report on a new member of the thioredoxin family of proteins from the filarial nematodeBrugia malayi,Bm-TRX-1, which defines a new subclass of 16-kDa thioredoxins that occur widely in nematodes, includingCaenorhabditis elegans. In addition to being larger than the thioredoxins found in mammalian and bacterial species, the putative active site sequence ofBm-TRX-1, WCPPC, does not conform to the highly conserved WCGPC reported for thioredoxins from mammals to bacteria. Interestingly, an allelic form ofBm-TRX-1 was identified with an active site sequence WCPQC, which appears to be unique to the thioredoxins from filarial species.Bm-TRX-1 was between 98% and 35% identical to thioredoxins from other nematodes and ≈20% identical to the thioredoxins from mammals andEscherichia coli. Bm-TRX-1 was constitutively transcribed throughout theB. malayilife cycle, andBm-TRX protein was detectable in somatic extracts and excretory-secretory products from adults and microfilariae. RecombinantBm-TRX-1 had thiodisulfide reductase activity, as measured by the reduction of insulin, and protected DNA from the nicking activity of oxygen radicals. Overexpression ofBm-TRX-1 in a human monocyte cell line negatively regulated tumor necrosis factor alpha-induced p38 mitogen-activated protein kinase activity, suggesting a possible role of the 16-kDaBm-TRX-1 in immunomodulation.
Production of Cellulose and Curli Fimbriae by Members of the Family
Enterobacteriaceae
Isolated from the Human Gastrointestinal Tract
Authors: Zogaj Xhavit , Bokranz Werner , Nimtz Manfred , Römling Ute 
Published: June 2003

ABSTRACT

Citrobacter
spp.,
Enterobacter
spp., and
Klebsiella
spp. isolated from the human gut were investigated for the biosynthesis of cellulose and curli fimbriae (
csg
). While
Citrobacter
spp. produced curli fimbriae and cellulose and
Enterobacter
spp. produced cellulose with various temperature-regulatory programs,
Klebsiella
spp. did not show pronounced expression of those extracellular matrix components. Investigation of multicellular behavior in two
Citrobacter
species and
Enterobacter sakazakii
showed an extracellular matrix, cell clumping, pellicle formation, and biofilm formation associated with the expression of cellulose and curli fimbriae. In those three strains, the
csgD-csgBA
region and the cellulose synthase gene
bcsA
were conserved. PCR screening for the presence of
csgD, csgA
and
bcsA
revealed that besides
Klebsiella pneumoniae
and
Klebsiella oxytoca,
all species investigated harbored the genetic information for expression of curli fimbriae and cellulose. Since
Citrobacter
spp.,
Enterobacter
spp., and
Klebsiella
spp. are frequently found to cause biofilm-related infections such as catheter-associated urinary tract infections, the human gut could serve as a reservoir for dissemination of biofilm-forming isolates.
Vaccine Efficacy of a Lysine Auxotroph of
Mycobacterium tuberculosis
Authors: Pavelka Martin S. , Chen Bing , Kelley Cynthia L. , Collins Frank M. , Jacobs William R. 
Published: June 2003

ABSTRACT

The in vivo growth phenotype and vaccine efficacy of a lysine auxotrophic mutant of
Mycobacterium tuberculosis
strain H37Rv are described. An immunization experiment using a mouse model with an aerosol challenge showed that two doses of the
M. tuberculosis
mutant were required to generate protection equivalent to that of the
Mycobacterium bovis
BCG vaccine.
Candida albicans
Septin Mutants Are Defective for Invasive Growth and Virulence
Authors: Warenda Amy J. , Kauffman Sarah , Sherrill Taylor P. , Becker Jeffrey M. , Konopka James B. 
Published: June 2003

ABSTRACT

Hyphal growth of
Candida albicans
is implicated as an important virulence factor for this opportunistic human pathogen. Septin proteins, a family of cytoskeletal elements that regulate membrane events and are important for proper morphogenesis of
C
.
albicans
, were examined for their role in tissue invasion and virulence in the mouse model of systemic infection. In vitro, septin mutants are only mildly defective for hyphal growth in liquid culture but display pronounced defects for invasive growth into agar. In vivo, the septin mutants were found to exhibit attenuated virulence. However, mice infected with the mutants displayed high fungal burdens in their kidneys without obvious symptoms of disease. Histological examination of infected kidneys revealed defects in organ invasion for the
cdc10Δ
and
cdc11Δ
deletion mutants, which displayed both reduced tissue penetration and noninvasive fungal masses. Thus, the septin proteins are necessary for invasive growth, which appears to be more important to the successful pathogenesis of
C
.
albicans
than hyphal growth alone.
CD44-Regulated Intracellular Proliferation ofListeria monocytogenes
Authors: Eriksson Emma , Dons Lone , Rothfuchs Antonio Gigliotti , Heldin Paraskevi , Wigzell Hans , Rottenberg Martin E. 
Published: June 2003

ABSTRACTCD44 has been implicated in immune and inflammatory processes. We have analyzed the role of CD44 in the outcome ofListeria monocytogenesinfection in murine bone marrow-derived macrophages (BMM). Surprisingly, a dramatically decreased intracellular survival ofL. monocytogeneswas observed in CD44−/−BMM. CD44−/−heart or lung fibroblast cultures also showed reduced bacterial levels. Moreover, livers from CD44−/−-infected mice showed diminished levels ofL. monocytogenes. In contrast, intracellular growth ofSalmonella entericaserovar Typhimurium was the same in CD44−/−and control BMM. The CD44-mediated increased bacterial proliferation was not linked to altered BMM differentiation or to secretion of soluble factors. CD44 did not mediate listerial uptake, and it played no role in bacterial escape from the primary phagosome or formation of actin tails. Furthermore, CD44-enhanced listerial proliferation occurred in the absence of intracellular bacterial spreading. Interestingly, coincubation of BMM with hyaluronidase or anti-CD44 antibodies that selectively inhibit hyaluronan binding increased intracellular listerial proliferation. Treatment of cells with hyaluronan, in contrast, diminished listerial growth and induced proinflammatory transcript levels. We suggest thatL. monocytogenestakes advantage of the CD44-mediated signaling to proliferate intracellularly, although binding of CD44 to certain ligands will inhibit such response.
Bordetella bronchiseptica
Persists in the Nasal Cavities of Mice and Triggers Early Delivery of Dendritic Cells in the Lymph Nodes Draining the Lower and Upper Respiratory Tract
Authors: Gueirard Pascale , Ave Patrick , Balazuc Anne-Marie , Thiberge Sabine , Huerre Michel , Milon Genevieve , Guiso Nicole 
Published: June 2003

ABSTRACT

Early after the intranasal instillation of
Bordetella bronchiseptica
into mice, not only are mature dendritic leukocytes recovered from lung parenchyma and bronchoalveolar lavage fluid but their numbers are also increased in the mediastinal lymph nodes and the nasal mucosa-associated lymphoid tissue. Later during the infectious process, the bacteria persist mainly in the nasal cavity.
The σ
B
Regulon Influences Internalization of
Staphylococcus aureus
by Osteoblasts
Authors: Nair Sean P. , Bischoff Markus , Senn Maria M. , Berger-Bächi Brigitte 
Published: June 2003

ABSTRACT

Individual strains of
Staphylococcus aureus
have different capacities to become internalized by osteoblasts. Here we report that the levels of σ
B
expressed by
S
.
aureus
correlate with the capacity of this bacterium to be internalized by osteoblasts. However, σ
B
is not essential for internalization and does not necessarily account for the differences in the capacities of strains to be internalized.
In Vivo Lysogenic Conversion of Tox
−
Streptococcus pyogenes
to Tox
+
with Lysogenic Streptococci or Free Phage
Authors: Broudy Thomas B. , Fischetti Vincent A. 
Published: June 2003

ABSTRACT

Temperate bacteriophage can transfer toxin-encoding genes between bacteria, often resulting in acquired pathogenicity. However, little is known regarding the effects of the eukaryotic host on the phage-pathogen interaction. Using
Streptococcus pyogenes
as a model, we demonstrate, both in vitro and in vivo, that the eukaryote mediates the efficient induction of toxin-encoding temperate phage and the resultant conversion of Tox
−
flora to Tox
+
. Furthermore, we show that both phage induction and subsequent conversion need not happen in the same mammalian host, as host-to-host phage transmission can result in toxigenic conversion within the secondary host. Ultimately, our findings demonstrate that the eukaryotic host serves as an essential component in the phage-mediated evolution of virulence within the microbial population.
Induction of Protective Immunity againstSchistosoma mansonivia DNA Priming and Boosting with the Large Subunit of Calpain (Sm-p80): Adjuvant Effects of Granulocyte-Macrophage Colony-Stimulating Factor and Interleukin-4
Authors: Siddiqui Afzal A. , Phillips Troy , Charest Hugues , Podesta Ron B. , Quinlin Martha L. , Pinkston Justin R. , Lloyd Jenny D. , Paz Michelle , Villalovos Rachael M. , Pompa Janet 
Published: June 2003

ABSTRACTConsiderable morbidity and mortality result from schistosomiasis, an affliction affecting an estimated 200 million people. Although schistosomicidal drugs and other control measures (including public hygiene and snail control) exist, the advent of an efficacious vaccine remains the most potentially powerful means for controlling this disease. We have targeted a vaccine candidate (large subunit of calpain, Sm-p80) because of its consistent immunogenicity, protective potential, and integral role in surface membrane biogenesis of schistosomes. Since surface membrane renewal appears to be one of the major phenomena employed by schistosomes to evade the host's immune system; an immune response directed against Sm-p80 should render the parasite susceptible to immune clearance from the host by both providing a focus of attack and by potentially impairing the membrane repair process. In the present study, we have employed DNA immunization protocols using Sm-p80 with plasmids encoding granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). Sm-p80 by itself provided 39% protection (P= ≤0.0001) against challenge infection in C57BL/6 mice. This protection was increased to 44% (P= ≤0.0001) when the plasmid encoding GM-CSF was coadministered with Sm-p80 DNA. Coinjection of plasmid DNA encoding IL-4 with Sm-p80 DNA yielded a protection level of 42% (P= ≤0.0001). Statistically, the protection conferred by including GM-CSF, but not IL-4, was significantly greater than that when only Sm-p80 was used. Sm-p80 DNA by itself elicited strong responses that include IgG2A and IgG2B antibody isotypes. The introduction of GM-CSF DNA with Sm-p80 DNA led to distinct increases in total IgG and IgG1 titers, whereas the coadministration of IL-4 DNA with Sm-p80 DNA resulted in a slight elevation of IgG1 and IgG3 titers and in some reduction of IgG2A and IgG2B titers. Our data again indicate that Sm-p80 can be an excellent candidate for a schistosomiasis vaccine.
Recombinant Soluble CD14 Reduces Severity of Intramammary Infection byEscherichia coli
Authors: Lee Jai-Wei , Paape Max J. , Elsasser Theodore H. , Zhao Xin 
Published: June 2003

ABSTRACTThe interaction among gram-negative bacteria, the innate immune system, and soluble CD14 (sCD14) has not been well documented. The effect of recombinant bovine sCD14 (rbosCD14) on milk somatic cell count (SCC), bacterial clearance, and cytokine production was investigated by using a bovine intramammaryEscherichia coliinfection model. We first determined whether rbosCD14 would increase the SCC during a lipopolysaccharide (LPS) challenge. Three quarters of each of six healthy lactating cows were injected with either 0.3 μg of LPS, 0.3 μg of LPS plus 100 μg of rbosCD14, or saline. In comparison with quarters injected with LPS alone, the SCC was twofold higher (P< 0.05) in quarters injected with LPS plus rbosCD14 after the challenge. We therefore hypothesized that whenE.colibacteria invade the mammary gland, sCD14 in milk would interact with LPS and rapidly recruit neutrophils from the blood to eliminate the bacteria before establishment of infection. To test this hypothesis, two quarters of each of nine healthy cows were challenged with either 50 CFU ofE.coliplus saline or 50 CFU ofE.coliplus 100 μg of rbosCD14. Quarters challenged withE.coliplus rbosCD14 had a more rapid recruitment of neutrophils, which was accompanied by a faster clearance of bacteria, lower concentrations of tumor necrosis factor alpha and interleukin-8 in milk, and milder clinical symptoms, than challenged quarters injected with saline. Results indicate that increasing the concentration of sCD14 in milk may be a potential strategy with which to prevent or reduce the severity of infection by coliform bacteria.
Disruption of the ICOS-B7RP-1 Costimulatory Pathway Leads to Enhanced Hepatic Immunopathology and Increased Gamma Interferon Production by CD4 T Cells in Murine Schistosomiasis
Authors: Rutitzky Laura I. , Özkaynak Engin , Rottman James B. , Stadecker Miguel J. 
Published: June 2003

ABSTRACTMorbidity and mortality in schistosomiasis are largely due to an immune response mediated by CD4 T lymphocytes. Since lymphocyte activation is shaped by costimulatory signals, the specific functions of different costimulatory pathways are of increasing interest. We now examined the role of the inducible costimulatory molecule (ICOS) and its ligand B7-related protein 1 (B7RP-1) in the experimental murine schistosome infection by blocking this costimulatory pathway with monoclonal antibody against ICOS, administered daily by intraperitoneal injection during the patent phase of the disease. The treated mice exhibited enhanced hepatic immunopathology characterized by enlarged egg granulomas and pronounced parenchymal inflammation with hepatocellular necrosis, resulting in elevated liver enzyme levels in serum. Most strikingly, there was a sharp increase in gamma interferon (IFN-γ) production by schistosome egg antigen-stimulated granuloma cells, bulk mesenteric lymph node (MLN) cells, and purified MLN CD4 T cells, which contrasted with a more discreet change in the Th2-type cytokines interleukin 4 (IL-4) and IL-10. These findings suggest that the ICOS-B7RP-1 costimulatory pathway serves primarily to control IFN-γ production, thereby promoting a cytokine environment conducive to limited hepatic damage.
TheDrosophila melanogasterToll Pathway Participates in Resistance to Infection by the Gram-Negative Human PathogenPseudomonas aeruginosa
Authors: Lau Gee W. , Goumnerov Boyan C. , Walendziewicz Cynthia L. , Hewitson Jennifer , Xiao Wenzhong , Mahajan-Miklos Shalina , Tompkins Ronald G. , Perkins Lizabeth A. , Rahme Laurence G. 
Published: June 2003

ABSTRACTPseudomonas aeruginosais a gram-negative pathogen that infects immunocompromised and cystic fibrosis patients. The molecular basis of the host-P. aeruginosainteraction and the effect of specificP. aeruginosavirulence factors on various components of the innate immunity pathways are largely unknown. We examine interactions betweenP. aeruginosavirulence factors and components of innate immunity response in theDrosophila melanogastermodel system to reveal the importance of the Toll signaling pathway in resistance to infection by theP. aeruginosahuman isolate PA14. Using the two PA14-isogenic mutantsplcSanddsbA, we show thatDrosophilaloss-of-function mutants of Spatzle, the extracellular ligand of Toll, and Dorsal and Dif, two NF-κB-like transcription factors, allow increasedP. aeruginosainfectivity within fly tissues. In contrast, a constitutively active Toll mutant and a loss-of-function mutant of Cactus, an IκB-like factor that inhibits the Toll signaling, reduce infectivity. Our finding that Dorsal activity is required to restrictP. aeruginosainfectivity inDrosophilaprovides direct in vivo evidence for Dorsal function in adult fly immunity. Additionally, our results provide the basis for future studies into interactions betweenP. aeruginosavirulence factors and components of the Toll signaling pathway, which is functionally conserved between flies and humans.
Infectious Agent and Immune Response Characteristics of Chronic Enterocolitis in Captive Rhesus Macaques
Authors: Sestak Karol , Merritt Christopher K. , Borda Juan , Saylor Elizabeth , Schwamberger Shelle R. , Cogswell Frank , Didier Elizabeth S. , Didier Peter J. , Plauche Gail , Bohm Rudolf P. , Aye Pyone P. , Alexa Pavel , Ward Richard L. , Lackner Andrew A. 
Published: June 2003

ABSTRACTChronic enterocolitis is the leading cause of morbidity in colonies of captive rhesus macaques (Macaca mulatta). This study's aim was to identify the common enteric pathogens frequently associated with chronic enterocolitis in normal, immunocompetent rhesus monkeys and to elucidate the influence of this clinical syndrome on the host immune system. We analyzed the fecal specimens from 100 rhesus macaques with or without clinical symptoms of chronic diarrhea. Retrospective analysis revealed an increased incidence ofCampylobacterspp. (Campylobacter coliandCampylobacter jejuni),Shigella flexneri,Yersinia enterocolitica, adenovirus, andStrongyloides fulleborniin samples collected from animals with chronic diarrhea (P< 0.05). The presence of additional enteric pathogens, such asEscherichia coli, carrying the eaeA intimin or Stx2c Shiga toxin virulence genes,Balantidium coli,Giardia lamblia,Enterocytozoon bieneusi, andTrichuris trichiurawas found in all animals regardless of whether diarrhea was present. In addition, the upregulation of interleukin-1α (IL-1α), IL-3, and tumor necrosis factor alpha cytokine genes, accompanied by an increased presence of activated (CD4+CD69+) T lymphocytes was found in gut-associated lymphoid tissues collected from animals with chronic enterocolitis and diarrhea in comparison with clinically healthy controls (P< 0.05). These data indicate that chronic enterocolitis and diarrhea are associated, in part, with a variety of enteric pathogens and highlight the importance of defining the microbiological status of nonhuman primates used for infectious disease studies. The data also suggest that chronic colitis in rhesus macaques may have potential as a model of inflammatory bowel disease in humans.
Linear and Circular Plasmid Content in
Borrelia burgdorferi
Clinical Isolates
Authors: Iyer Radha , Kalu Ogori , Purser Joye , Norris Steven , Stevenson Brian , Schwartz Ira 
Published: June 2003

ABSTRACT

The genome of
Borrelia burgdorferi
, the etiologic agent of Lyme disease, is composed of a linear chromosome and more than 20 linear and circular plasmids. Typically, plasmid content analysis has been carried out by pulsed-field gel electrophoresis and confirmed by Southern hybridization. However, multiple plasmids of virtually identical sizes (e.g., lp28 and cp32) complicate the interpretation of such data. The present study was undertaken to investigate the complete plasmid complements of
B. burgdorferi
clinical isolates cultivated from patients from a single region where early Lyme disease is endemic. A total of 21 isolates obtained from the skin biopsy or blood samples of Lyme disease patients were examined for their complete plasmid complements by Southern hybridization and plasmid-specific PCR analysis. All clinical isolates harbored at least six of the nine previously characterized cp32s. Fourteen isolates harbored all B31-like linear plasmids, and seven isolates simultaneously lacked lp56, lp38, and some segments of lp28-1. The distinctive plasmid profile observed in these seven isolates was specific to organisms that had ribosomal spacer type 2 and pulsed-field gel type A, which implies a clonal origin for this genotype. The presence of nearly identical complements of multiple linear and circular plasmids in all of the human isolates suggests that these plasmids may be particularly necessary for infection, adaptation, and/or maintenance in the infected host.
Antibody Specificities and Effect of Meningococcal Carriage in Icelandic Teenagers Receiving the Norwegian Serogroup B Outer Membrane Vesicle Vaccine
Authors: Wedege Elisabeth , Kuipers Betsy , Bolstad Karin , van Dijken Harry , Frøholm L. Oddvar , Vermont Clementien , Caugant Dominique A. , van den Dobbelsteen Germie 
Published: June 2003

ABSTRACT

Antibody specificities of pre- and postvaccination serum samples from 40 (53%) teenagers who received three doses of the Norwegian
Neisseria meningitidis
serogroup B vaccine (B:15:P1.7,16) during a previous trial in Iceland (Perkins et al., J. Infect. Dis.
177:
683-691, 1998) were analyzed with serum bactericidal activity (SBA) and immunoblotting assays with reference and isogenic meningococcal H44/76 vaccine strains. The H44/76 variants demonstrated significant vaccine-induced SBA to P1.7,16 PorA and Opc but not to PorB, Opa5.5, and a heterologous PorA protein. On blots, immunoglobulin G levels to all these proteins increased significantly after vaccination. Measurement of SBA to the two main variable regions (P1.7 and P1.16) on the P1.7,16 PorA with PorA deletion mutants revealed significantly higher activity to the P1.7,− and P1.−,16 mutants compared to the P1.7,16 strain, indicating exposure of new accessible epitopes. Only 12 (30%) serum samples showed distinct decreases with these or the P1.−,− mutant, with most samples containing SBA to the P1.7 and P1.16 combination. In contrast, P1.16-specific antibodies were mainly found on blots. Thirteen of the vaccinees (32.5%) were carriers of meningococci at the time of the third dose, of whom four (30.8%) harbored strains of the ET-5 complex. Carriage of P1.15 strains was generally reflected in ≥4-fold increases in SBA and distinct immunoglobulin G binding to the P1.19,15 PorA on blots. Although vaccination did not elicit bactericidal activity to the serotype 15 PorB, most carriers of serotype 15 strains showed ≥4-fold increases in SBA to this antigen.