bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antimalarial Activity of a New Stilbene Glycoside from
Parthenocissus tricuspidata
in Mice
Authors: Park Won-Hwan , Lee Sung-Jae , Moon Hyung-In 
Published: July 2008

ABSTRACT

A novel stilbene glycoside [piceid-(1→6)-β-
d
-glucopyranoside; PBG] from
Parthenocissus tricuspidata
was tested in vivo against
Plasmodium berghei
. PBG exhibited significant blood schizontocidal activity in a 4-day early infection, a repository evaluation, and an established infection, with a significant mean survival time comparable to that obtained with the standard drug, chloroquine (5 mg·kg
−1
·day
−1
).
Real-Time PCR and Statistical Analyses of
acrAB
and
ramA
Expression in Clinical Isolates of
Klebsiella pneumoniae
Authors: Ruzin Alexey , Immermann Frederick W. , Bradford Patricia A. 
Published: July 2008

ABSTRACT

Clinical isolates of
Klebsiella pneumoniae
were tested for a correlation between tigecycline MIC and expression of
ramA
by using real-time PCR. At MICs of 4 and 8 μg/ml, the expression of
ramA
was statistically significantly different from MICs of 2 μg/ml or less, supporting the tigecycline susceptibility breakpoint of ≤2 μg/ml for
K. pneumoniae
.
Comparative In Vitro Anti-Hepatitis C Virus Activities of a Selected Series of Polymerase, Protease, and Helicase Inhibitors
Authors: Paeshuyse Jan , Vliegen Inge , Coelmont Lotte , Leyssen Pieter , Tabarrini Oriana , Herdewijn Piet , Mittendorfer Harald , Easmon Johnny , Cecchetti Violetta , Bartenschlager Ralf , Puerstinger Gerhard , Neyts Johan 
Published: July 2008

ABSTRACTWe report here a comparative study of the anti-hepatitis C virus (HCV) activities of selected (i) nucleoside polymerase, (ii) nonnucleoside polymerase, (iii) α,γ-diketo acid polymerase, (iv) NS3 protease, and (v) helicase inhibitors, as well as (vi) cyclophilin binding molecules and (vii) alpha 2b interferon in four different HCV genotype 1b replicon systems.
The Commensal
Streptococcus salivarius
K12 Downregulates the Innate Immune Responses of Human Epithelial Cells and Promotes Host-Microbe Homeostasis
Authors: Cosseau Celine , Devine Deirdre A. , Dullaghan Edie , Gardy Jennifer L. , Chikatamarla Avinash , Gellatly Shaan , Yu Lorraine L. , Pistolic Jelena , Falsafi Reza , Tagg John , Hancock Robert E. W. 
Published: July 2008

ABSTRACT

Streptococcus salivarius
is an early colonizer of human oral and nasopharyngeal epithelia, and strain K12 has reported probiotic effects. An emerging paradigm indicates that commensal bacteria downregulate immune responses through the action on NF-κB signaling pathways, but additional mechanisms underlying probiotic actions are not well understood. Our objective here was to identify host genes specifically targeted by K12 by comparing their responses with responses elicited by pathogens and to determine if
S. salivarius
modulates epithelial cell immune responses. RNA was extracted from human bronchial epithelial cells (16HBE14O- cells) cocultured with K12 or bacterial pathogens. cDNA was hybridized to a human 21K oligonucleotide-based array. Data were analyzed using ArrayPipe, InnateDB, PANTHER, and oPOSSUM. Interleukin 8 (IL-8) and growth-regulated oncogene alpha (Groα) secretion were determined by enzyme-linked immunosorbent assay. It was demonstrated that
S. salivarius
K12 specifically altered the expression of 565 host genes, particularly those involved in multiple innate defense pathways, general epithelial cell function and homeostasis, cytoskeletal remodeling, cell development and migration, and signaling pathways. It inhibited baseline IL-8 secretion and IL-8 responses to LL-37,
Pseudomonas aeruginosa
, and flagellin in epithelial cells and attenuated Groα secretion in response to flagellin. Immunosuppression was coincident with the inhibition of activation of the NF-κB pathway. Thus, the commensal and probiotic behaviors of
S. salivarius
K12 are proposed to be due to the organism (i) eliciting no proinflammatory response, (ii) stimulating an anti-inflammatory response, and (iii) modulating genes associated with adhesion to the epithelial layer and homeostasis.
S. salivarius
K12 might thereby ensure that it is tolerated by the host and maintained on the epithelial surface while actively protecting the host from inflammation and apoptosis induced by pathogens.
In Vivo Demonstration and Quantification of Intracellular
Bacillus anthracis
in Lung Epithelial Cells
Authors: Russell Brooke H. , Liu Qing , Jenkins Sarah A. , Tuvim Michael J. , Dickey Burton F. , Xu Yi 
Published: July 2008

ABSTRACT

Inhalational anthrax is initiated by the entry of
Bacillus anthracis
spores into the lung. A critical early event in the establishment of an infection is the dissemination of spores from the lung. Using in vitro cell culture assays, we previously demonstrated that
B. anthracis
spores are capable of entering into epithelial cells of the lung and crossing a barrier of lung epithelial cells without apparent disruption of the barrier integrity, suggesting a novel portal for spores to disseminate from the lung. However, in vivo evidence for spore uptake by epithelial cells has been lacking. Here, using a mouse model, we present evidence that
B. anthracis
spores are taken up by lung epithelial cells in vivo soon after spores are delivered into the lung. Immunofluorescence staining of thin sections of lungs from spore-challenged BALB/c mice revealed that spores were associated with the epithelial surfaces in the airway and the alveoli at 2 and 4 h postinoculation. Confocal analysis further indicated that some of the associated spores were surrounded by F-actin, demonstrating intracellular localization. These observations were further confirmed and substantiated by a quantitative method that first isolated lung cells from spore-challenged mice and then stained these cells with antibodies specific for epithelial cells and spores. The results showed that substantial amounts of spores were taken up by lung epithelial cells in vivo. These data, combined with those in our previous reports, provided powerful evidence that the lung epithelia were directly targeted by
B. anthracis
spores at early stages of infection.
Characterization of Complement Factor H Binding toYersinia enterocoliticaSerotype O:3
Authors: Biedzka-Sarek Marta , Jarva Hanna , Hyytiäinen Heidi , Meri Seppo , Skurnik Mikael 
Published: July 2008

ABSTRACTA number of bacteria bind factor H (FH), the negative regulator of the alternative complement pathway, to avoid complement-mediated killing. Here we show that a gram-negative enteric pathogen,Yersinia enterocoliticaserotype O:3, uses two virulence-related outer membrane (OM) proteins to bind FH. WithY. enterocoliticaO:3 mutant strains displaying different combinations of surface factors relevant to complement resistance, we demonstrated that the major receptor for FH is the OM protein YadA. Another OM protein, Ail, also contributes to FH binding provided that it is not blocked by distal parts of the lipopolysaccharide (i.e., the O antigen and the outer core hexasaccharide). Importantly, we demonstrated that surface-bound FH was functional; both YadA- and Ail-bound FH displayed cofactor activity for factor I-mediated cleavage of C3b. With truncated recombinant FH constructs, we located the binding site of Ail specifically to short consensus repeats 6 and 7 of FH, while YadA showed a novel type of FH-binding pattern and appears to bind FH throughout the entire FH molecule. We thus conclude thatY. enterocolitica, via YadA and Ail, recruits functionally active FH to its surface. FH binding appears to be an important mechanism of the complement resistance of this pathogen.
The Failure of Immune Response Evasion by Linear Plasmid 28-1-Deficient
Borrelia burgdorferi
Is Attributable to Persistent Expression of an Outer Surface Protein
Authors: Embers Monica E. , Alvarez Xavier , Ooms Tara , Philipp Mario T. 
Published: July 2008

ABSTRACT

Infectivity and persistence by
Borrelia burgdorferi
, the etiologic agent of Lyme disease, rely stringently on regulatory events. Among these is the downregulation of lipoprotein antigen expression, exemplified by outer surface protein C (OspC), at the advent of specific immunity in the mammalian host.
B. burgdorferi
spirochetes that lack the linear plasmid 28-1 (lp28-1) succumb to the host's immune response. We thus explored the notion that these two phenomena were related—that lp28-1
−
organisms fail to downregulate
ospC
and thus are cleared following the appearance of anti-OspC antibody in the murine host. The lp-28-1
−
isolate and a wild-type (wt) isolate bearing the complete set of plasmids were grown in dialysis membrane chambers that were implanted into rat peritoneal cavities. Analysis of mRNA and protein from these cultures showed that OspC expression levels by lp28-1
−
organisms are abnormally high in vivo. A time course analysis of
ospC
expression in tissues following infection indicates also that temporal diminution of the dominant antigen OspC is impaired in lp28-1
−
spirochetes. Finally, passive transfer of monoclonal OspC-specific antibody into SCID mice 8 days postinfection cleared lp28-1
−
spirochetes, yet the wt organisms persisted in a majority of animals. These findings indicate that incomplete repression of OspC by lp28-1
−
organisms renders them susceptible to immune-mediated clearance. The lp28-1 plasmid must harbor one or more genes involved in OspC downregulation.
Inhibition of
Salmonella enterica
Serovar Typhimurium Motility and Entry into Epithelial Cells by a Protective Antilipopolysaccharide Monoclonal Immunoglobulin A Antibody
Authors: Forbes Stephen J. , Eschmann Marisa , Mantis Nicholas J. 
Published: July 2008

ABSTRACT

Secretory immunoglobulin A (SIgA) antibodies directed against the O antigen of lipopolysaccharide (LPS) are the primary determinants of mucosal immunity to gram-negative enteric pathogens. However, the underlying mechanisms by which these antibodies interfere with bacterial colonization and invasion of intestinal epithelial cells are not well understood. In this study, we report that Sal4, a protective, anti-O5-specific monoclonal IgA, is a potent inhibitor of
Salmonella enterica
serovar Typhimurium flagellum-based motility. Using video light microscopy, we observed that Sal4 completely and virtually instantaneously “paralyzed” laboratory and clinical strains of serovar Typhimurium. Sal4-mediated motility arrest preceded and occurred independently of agglutination. Polyclonal anti-LPS IgG antibodies and F(ab)
2
fragments were as potent as was Sal4 at impeding bacterial motility, whereas monovalent Fab fragments were 5- to 10-fold less effective. To determine whether motility arrest can fully account for Sal4's protective capacity in vitro, we performed epithelial cell infection assays in which the requirement for flagellar motility in adherence and invasion was bypassed by centrifugation. Under these conditions, Sal4-treated serovar Typhimurium cells remained noninvasive, revealing that the monoclonal IgA, in addition to interfering with motility, has an effect on bacterial uptake into epithelial cells. Sal4 did not, however, inhibit bacterial uptake into mouse macrophages, indicating that the antibody interferes specifically with
Salmonella
pathogenicity island 1 (SPI-1)-dependent, but not SPI-1-independent, entry into host cells. These results reveal a previously unrecognized capacity of SIgA to “disarm” microbial pathogens on mucosal surfaces and prevent colonization and invasion of the intestinal epithelium.
Characteristics of Biofilm Formation byStreptococcus mutansin the Presence of Saliva
Authors: Ahn Sug-Joon , Ahn Sang-Joon , Wen Zezhang T. , Brady L. Jeannine , Burne Robert A. 
Published: July 2008

ABSTRACTInteractions between salivary agglutinin and the adhesin P1 ofStreptococcus mutanscontribute to bacterial aggregation and mediate sucrose-independent adherence to tooth surfaces. We have examined biofilm formation byS. mutansUA159, and derivative strains carrying mutations affecting the localization or expression of P1, in the presence of fluid-phase or adsorbed saliva or salivary agglutinin preparations. Whole saliva- and salivary agglutinin-induced aggregation ofS. mutanswas adversely affected by the loss of P1 and sortase (SrtA) but not by the loss of trigger factor (RopA). Fluid-phase salivary agglutinin and, to a lesser extent, immobilized agglutinin inhibited biofilm development byS. mutansin the absence of sucrose, and whole saliva was more effective at decreasing biofilm formation than salivary agglutinin. Inhibition of biofilm development by salivary agglutinin was differently influenced by particular mutations, with the P1-deficient strain displaying a greater inhibition of biofilm development than the SrtA- or RopA-deficient strains. As expected, biofilm-forming capacities of all strains in the presence of salivary preparations were markedly enhanced in the presence of sucrose, although biofilm formation by the mutants was less efficient than that by the parental strain. Aeration strongly inhibited biofilm development, and the presence of salivary components did not restore biofilm formation in aerated conditions. The results disclose a potent ability of salivary constituents to moderate biofilm formation byS. mutansthrough P1-dependent and P1-independent pathways.
Outer Membrane Antigens of the UropathogenProteus mirabilisRecognized by the Humoral Response during Experimental Murine Urinary Tract Infection
Authors: Nielubowicz Greta R. , Smith Sara N. , Mobley Harry L. T. 
Published: July 2008

ABSTRACTProteus mirabilis, a gram-negative bacterium, is a frequent cause of complicated urinary tract infections in those with functional or anatomical abnormalities or those subject to long-term catheterization. To systematically identify surface-exposed antigens as potential vaccine candidates, proteins in the outer membrane fraction of bacteria were separated by two-dimensional gel electrophoresis and subjected to Western blotting with sera from mice experimentally infected withP. mirabilis. Protein spots reactive with sera were identified by mass spectrometry, which in conjunction with the newly completed genome sequence ofP. mirabilisHI4320, was used to identify surface-exposed antigens. Culture conditions that may mimic in vivo conditions more closely than Luria broth (growth in human urine and under iron limitation and osmotic stress) were also used. Thirty-seven antigens to which a humoral response had been mounted, including 23 outer membrane proteins, were identified. These antigens are presumably expressed during urinary tract infection. Protein targets that are both actively required for virulence and antigenic may serve as protective antigens for vaccination; thus, five representative antigens were selected for use in virulence studies. Strains ofP. mirabiliswith mutations in three of the corresponding genes (the PMI0047 gene,rafY, andfadL) were not attenuated in the murine model of urinary tract infection. Putative iron acquisition proteins PMI0842 and PMI2596, however, both contribute to fitness in the urinary tract and thus emerge as vaccine candidates.
Effects of
Clostridium perfringens
Beta-Toxin on the Rabbit Small Intestine and Colon
Authors: Vidal Jorge E. , McClane Bruce A. , Saputo Juliann , Parker Jaquelyn , Uzal Francisco A. 
Published: July 2008

ABSTRACT

Clostridium perfringens
type B and type C isolates, which produce beta-toxin (CPB), cause fatal diseases originating in the intestines of humans or livestock. Our previous studies demonstrated that CPB is necessary for type C isolate CN3685 to cause bloody necrotic enteritis in a rabbit ileal loop model and also showed that purified CPB, in the presence of trypsin inhibitor (TI), can reproduce type C pathology in rabbit ileal loops. We report here a more complete characterization of the effects of purified CPB in the rabbit small and large intestines. One microgram of purified CPB, in the presence of TI, was found to be sufficient to cause significant accumulation of hemorrhagic luminal fluid in duodenal, jejunal, or ileal loops treated for 6 h with purified CPB, while no damage was observed in corresponding loops receiving CPB (no TI) or TI alone. In contrast to the CPB sensitivity of the small intestine, the colon was not affected by 6 h of treatment with even 90 μg of purified CPB whether or not TI was present. Time course studies showed that purified CPB begins to induce small intestinal damage within 1 h, at which time the duodenum is less damaged than the jejunum or ileum. These observations help to explain why type B and C infections primarily involve the small intestine, establish CPB as a very potent and fast-acting toxin in the small intestines, and confirm a key role for intestinal trypsin as an innate intestinal defense mechanism against CPB-producing
C. perfringens
isolates.
Immunological Dominance of
Trypanosoma cruzi
Tandem Repeat Proteins
Authors: Goto Yasuyuki , Carter Darrick , Reed Steven G. 
Published: July 2008

ABSTRACT

Proteins with tandem repeat (TR) domains have been found in various protozoan parasites, often acting as targets of B-cell responses. However, the extent of the repeats within
Trypanosoma cruzi
, the causative agent of Chagas’ disease, has not been examined well. Here, we present a systematic survey of the TR genes found in
T. cruzi
, in comparison with other organisms. Although the characteristics of TR genes varied from organism to organism, the presence of genes having large TR domains was unique to the trypanosomatids examined, including
T. cruzi
. Sequence analyses of
T. cruzi
TR genes revealed their divergency; they do not share such characteristics as sequence similarity or biased cellular location predicted by the presence of a signal sequence or transmembrane domain(s). In contrast,
T. cruzi
TR proteins seemed to possess significant antigenicity. A number of previously characterized
T. cruzi
antigens were detected by this computational screening, and several of those antigens contained a large TR domain. Further analyses of the
T. cruzi
genome demonstrated that previously uncharacterized TR proteins in this organism may also be immunodominant. Taken together,
T. cruzi
is rich in large TR domain-containing proteins with immunological significance; it is worthwhile further analyzing such characteristics of TR proteins as the copy number and consensus sequence of the repeats to determine whether they might contribute to the biological variability of
T. cruzi
strains with regard to induced immunological responses, host susceptibility, disease outcomes, and pathogenicity.
Salmonella enterica
Serovar Typhimurium NiFe Uptake-Type Hydrogenases Are Differentially Expressed In Vivo
Authors: Zbell Andrea L. , Maier Susan E. , Maier Robert J. 
Published: July 2008

ABSTRACT

Salmonella enterica
serovar Typhimurium, a common enteric pathogen, possesses three NiFe uptake-type hydrogenases. The results from mouse infection studies suggest that the H
2
oxidation capacity provided by these hydrogenases is important for virulence. Since the three enzymes are similar in structure and function, it may be expected that they are utilized under different locations and times during an infection. A recombination-based method to examine promoter activity in vivo (RIVET) was used to determine hydrogenase gene expression in macrophages, polymorphonuclear leukocyte (PMN)-like cells, and a mouse model of salmonellosis. The
hyd
and
hya
promoters showed increased expression in both murine macrophages and human PMN-like cells compared to that in the medium-only controls. Quantitative reverse transcription-PCR results suggested that
hyb
is also expressed in phagocytes. A nonpolar
hya
mutant was compromised for survival in macrophages compared to the wild type. This may be due to lower tolerance to acid stress, since the
hya
mutant was much more acid sensitive than the wild type. In addition,
hya
mutant cells were internalized by macrophages the same as wild-type cells. Mouse studies (RIVET) indicate that
hyd
is highly expressed in the liver and spleen early during infection but is expressed poorly in the ileum in infected animals. Late in the infection, the
hyd
genes were expressed at high levels in the ileum as well as in the liver and spleen. The
hya
genes were expressed at low levels in all locations tested. These results suggest that the hydrogenases are used to oxidize hydrogen in different stages of an infection.
The Absence of Cutaneous Lymph Nodes Results in a Th2 Response and Increased Susceptibility toLeishmania majorInfection in Mice
Authors: Ehrchen Jan M. , Roth Johannes , Roebrock Kirsten , Varga Georg , Domschke Wolfram , Newberry Rodney , Sorg Clemens , Müller-Tidow Carsten , Sunderkötter Cord , Kucharzik Torsten , Spahn Thomas W. 
Published: July 2008

ABSTRACTLymph nodes (LNs) are important sentinel organs where antigen-presenting cells interact with T cells to induce adaptive immune responses. In cutaneous infection of mice withLeishmania major, resistance depends on the induction of a T-helper-cell-1 (Th1)-mediated cellular immune response in draining, peripheral LNs. We investigated whether draining, peripheral LNs are absolutely required for resistance againstL. majorinfection. We investigated the course of experimental leishmaniasis in wild-type (wt) mice lacking peripheral LNs (pLNs), which we generated by in utero blockade of membrane-bound lymphotoxin, and in mice lacking pLNs or all LNs due to genetic deletion of lymphotoxin ligands or receptors. wt mice of the resistant C57BL/6 strain without local skin-draining LNs were still able to generate specific T-cell responses, but this yielded Th2 cells. This switch to a Th2 response resulted in severe systemic infection. We also confirmed these results with mice lacking pLNs due to genetic depletion of lymphotoxin-β. The complete absence of LNs due to a genetic depletion of the lymphotoxin-β receptor also resulted in a marked deterioration of disease and a Th2 response. Thus, in the absence of pLNs, anL. major-specific Th2 response is induced in the remaining secondary lymphoid organs, such as the spleen and non-skin-draining LNs. This indicates a critical requirement for pLNs to induce protective Th1 immunity and suggests that whether Th1 or Th2 priming to the same antigen occurs depends on the site of the primary antigen recognition.
Serum Insulin-Like Growth Factor-I and Platelet-Derived Growth Factor as Biomarkers of Breast Cancer Prognosis
Authors: Pasanisi Patrizia , Venturelli Elisabetta , Morelli Daniele , Fontana Luigi , Secreto Giorgio , Berrino Franco 
Published: July 2008

AbstractEpidemiologic studies have shown that growth factors and inflammatory mechanisms may affect breast cancer risk and prognosis. The present analysis on 110 postmenopausal breast cancer patients tested if serum insulin-like growth factor I (IGF-I), platelet-derived growth factor (PDGF), fructosamine, and C-reactive protein, a serum marker of inflammation, are associated with breast cancer relapse. The risk of adverse events after 5.5 years of follow-up was examined by Cox proportional hazards modeling, controlling for hormone receptor status, stage at diagnosis, and for body weight and serum testosterone level, which were known to significantly affect prognosis. PDGF and, to a lesser extent, IGF-I were positively but not significantly associated with the risk of breast cancer recurrence. By combining PDGF and IGF-I, however, the adjusted hazard ratio of recurrence among the women with both PDGF and IGF-I levels &gt; their median values (respectively, 9.3 and 174.4 ng/mL) was 6.4 (95% confidence interval, 1.5-26.7) compared with the women with PDGF and IGF-I levels ≤ their median values. Fructosamine and C-reactive protein were not associated with recurrences. The results suggest that PDGF may be an important prognostic factor for breast cancer and that IGF-I may increase the risk of recurrence in the presence of high PDGF levels. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1719–22)