bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Novel Parainfluenza Virus Hemagglutinin-Neuraminidase Inhibitor BCX 2798 Prevents Lethal Synergism between a Paramyxovirus and
Streptococcus pneumoniae
Authors: Alymova Irina V. , Portner Allen , Takimoto Toru , Boyd Kelli L. , Babu Y. Sudhakara , McCullers Jonathan A. 
Published: December 2004

ABSTRACT

An association exists between respiratory viruses and bacterial infections. Prevention or treatment of the preceding viral infection is a logical goal for reducing this important cause of morbidity and mortality. The ability of the novel, selective parainfluenza virus hemagglutinin-neuraminidase inhibitor BCX 2798 to prevent the synergism between a paramyxovirus and
Streptococcus pneumoniae
was examined in this study. A model of secondary bacterial pneumonia after infection with a recombinant Sendai virus whose hemagglutinin-neuraminidase gene was replaced with that of human parainfluenza virus type 1 [rSV(hHN)] was established in mice. Challenge of mice with a sublethal dose of
S. pneumoniae
7 days after a sublethal infection with rSV(hHN) (synergistic group) caused 100% mortality. Bacterial infection preceding viral infection had no effect on survival. The mean bacterial titers in the synergistic group were significantly higher than in mice infected with bacteria only. The virus titers were similar in mice infected with rSV(hHN) alone and in dually infected mice. Intranasal administration of BCX 2798 at 10 mg/kg per day to the synergistic group of mice starting 4 h before virus infection protected 80% of animals from death. This effect was accompanied by a significant reduction in lung viral and bacterial titers. Treatment of mice 24 h after the rSV(hHN) infection showed no protection against synergistic lethality. Together, our results indicate that parainfluenza viruses can prime for secondary bacterial infections. Prophylaxis of parainfluenza virus infections with antivirals might be an effective strategy for prevention of secondary bacterial complications in humans.
dfrA20
, a Novel Trimethoprim Resistance Gene from
Pasteurella multocida
Authors: Kehrenberg Corinna , Schwarz Stefan 
Published: December 2004

ABSTRACT

A novel trimethoprim resistance gene, designated
dfrA20
, was detected on the 11-kb plasmid pCCK154 from
Pasteurella multocida
. The
dfrA20
gene codes for a dihydrofolate reductase of 169 amino acids. Sequence comparisons revealed that the DfrA20 protein differed distinctly from all dihydrofolate reductases known so far.
In-House Phage Amplification Assay Is a Sound Alternative for Detecting Rifampin-Resistant
Mycobacterium tuberculosis
in Low-Resource Settings
Authors: Símboli Norberto , Takiff Howard , McNerney Ruth , López Beatriz , Martin Anandi , Palomino Juan Carlos , Barrera Lucía , Ritacco Viviana 
Published: December 2004

ABSTRACT

An in-house mycobacteriophage amplification assay for detecting rifampin-resistant
Mycobacterium tuberculosis
showed 100% sensitivity, 97.7% specificity, and 95.2% predictive value for resistance in a test of 129 isolates from a hot spot area of multidrug-resistant
M. tuberculosis
. The applicability of the test was demonstrated in the routine work flow of a low-resource reference laboratory.
In Vivo Resistance of a Laboratory-Selected
Aspergillus fumigatus
Isolate to Amphotericin B
Authors: Manavathu Elias K. , Cutright Jessica L. , Chandrasekar Pranatharthi H. 
Published: December 2004

ABSTRACT

The fungal burdens (number of CFU per pair of lungs) in mice infected with
Aspergillus fumigatus
AB16.4 (for which the amphotericin B [AMB] MIC was elevated) and W73355 (drug-susceptible parent) were reduced by 21 and 81%, respectively, after 5 days of AMB treatment (2 mg/kg/day), indicating that AB16.4 also shows reduced susceptibility to AMB in a murine pulmonary aspergillosis model.
Characterization of In
100
, a New Integron Carrying a Metallo-β-Lactamase and a Carbenicillinase, from
Pseudomonas aeruginosa
Authors: Quinteira Sandra , Sousa João Carlos , Peixe Luísa 
Published: December 2004

ABSTRACT

In
100
, a new integron carrying a carbapenemase gene (
bla
VIM-2
) associated with a carbenicillinase (
blaP1b
) and aminoglycoside resistance genes (
aacA4
and
aadA2
), was detected in a
Pseudomonas aeruginosa
clinical isolate. The particular gene cassette organization of In
100
seems to reflect the evolution of antibiotic usage in therapeutics.
Emergence of Plasmid-Mediated Quinolone Resistance in
Escherichia coli
in Europe
Authors: Mammeri Hedi , Van De Loo Marc , Poirel Laurent , Martinez-Martinez Luis , Nordmann Patrice 
Published: December 2004

ABSTRACT

Although quinolone resistance results mostly from chromosomal mutations, it may also be mediated by a plasmid-encoded
qnr
gene in members of the family
Enterobacteriaceae
. Thus, 297 nalidixic-acid resistant strains of 2,700
Escherichia coli
strains that had been isolated at the Bicêtre Hospital (Le Kremlin-Bicêtre, France) in 2003 were screened for
qnr
by PCR. A single
E. coli
isolate that carried a ca. 180-kb conjugative plasmid encoding a
qnr
determinant was identified. It conferred low-level resistance to quinolones and was associated with a chromosomal mutation in subunit A of the topoisomerase II gene. The
qnr
gene was located on a
sul1
-type class 1 integron just downstream of a conserved region (CR) element (CR1) comprising the Orf513 recombinase. Promoter sequences for
qnr
expression overlapped the extremity of CR1, indicating the role of CR1 in the expression of antibiotic resistance genes. This integron was different from other
qnr
-positive
sul1
-type integrons identified in American and Chinese enterobacterial isolates. In addition, plasmid pQR1 carried another class 1 integron that was identical to In
53
from
E. coli
. The latter integron possessed a series of gene cassettes, including those coding for the extended-spectrum β-lactamase VEB-1, the rifampin ADP ribosyltransferase ARR-2, and several aminoglycoside resistance markers. This is the first report of plasmid-mediated quinolone resistance in Europe associated with an unknown level of plasmid-mediated multidrug resistance in
Enterobacteriaceae
.
Distribution of Antimicrobial Resistance and Virulence-Related Genes among Brazilian Group B Streptococci Recovered from Bovine and Human Sources
Authors: Duarte Rafael S. , Bellei Bruna C. , Miranda Otávio P. , Brito Maria A. V. P. , Teixeira Lúcia M. 
Published: December 2004

ABSTRACT

In the present report we describe the characteristics of 189 antimicrobial-resistant
Streptococcus agalactiae
isolates from bovine (38 isolates) and human (151 isolates) sources. All the strains were resistant to tetracycline (TET), and 16 (8.5%) were also resistant to erythromycin, corresponding to 23.7% of the TET-resistant bovine isolates and 4.6% of the TET-resistant human isolates. The
tet
(O),
erm
(B), and
mreA
resistance-related genes, as well as the
bca
and
scpB
virulence-related genes, were the most frequent among the bovine isolates, while the
tet
(M),
erm
(A),
mreA
,
bca
,
lmb
, and
scpB
genes were the most prevalent among the isolates from humans. Although a few major clusters were observed, pulsed-field gel electrophoresis results revealed a variety of profiles, reflecting the substantial genetic diversity among strains of this species isolated from either humans or bovines.
Acute-Phase Concentrations of Lipopolysaccharide (LPS)-Binding Protein Inhibit Innate Immune Cell Activation by Different LPS Chemotypes via Different Mechanisms
Authors: Hamann Lutz , Alexander Christian , Stamme Cordula , Zähringer Ulrich , Schumann Ralf R. 
Published: December 2004

ABSTRACTThe chain length of bacterial lipopolysaccharide (LPS) is a crucial factor for host-pathogen interaction during bacterial infection. While rough (R)-type and smooth (S)-type LPSs have been shown to differ in their ability to interact with the bactericidal/permeability-increasing protein, little is known about the differential mode of interaction with the acute-phase reactant LPS-binding protein (LBP). At lower concentrations, LBP catalyzes the binding of LPS to CD14 and enhances LPS-induced cellular activation via Toll-like receptor 4. In humans, however, concentrations of LBP in serum increase during an acute-phase response, and these LBP concentrations exhibit inhibitory effects in terms of cellular activation. The mechanisms of inhibition of LPS effects by LBP are not completely understood. Here, we report that human high-dose LBP (hd-LBP) suppresses binding of both R-type and S-type LPS to CD14 and inhibits LPS-induced nuclear translocation of NF-κB, although cellular uptake of R-type LPS was found to be increased by hd-LBP. In contrast, we found that hd-LBP enhanced the binding and uptake of S-type LPS only under serum-free conditions, whereas in the presence of serum, hd-LBP inhibited cellular binding and uptake. This inhibitory effect of serum could be mimicked by the addition of purified high-density lipoprotein (HDL) to serum-free medium, indicating an LBP-mediated transfer of preferentially S-type LPS to plasma lipoproteins such as HDL. A complete understanding of the host's mechanisms to modulate the proinflammatory effects of LPS will most likely help in the understanding of inflammation and infection and may lead to novel therapeutic intervention strategies.
Depletion of Complement Has Distinct Effects on the Primary and Secondary Antibody Responses to a Conjugate of Pneumococcal Serotype 14 Capsular Polysaccharide and a T-Cell-Dependent Protein Carrier
Authors: Test Samuel T. , Mitsuyoshi Joyce K. , Hu Yong 
Published: December 2004

ABSTRACTComplement activation plays a critical role in the immune response to T-cell-dependent and T-cell-independent antigens. However, the effect of conjugation of T-cell-dependent protein carriers to T-cell-independent type 2 antigens on the requirement for complement in the humoral immune response to such antigens remains unknown. We studied the role of complement activation on the antibody response of BALB/c mice immunized with the T-cell-independent type 2 antigen serotype 14 pneumococcal capsular polysaccharide (PPS14), either in unmodified form or conjugated to ovalbumin (OVA). In mice immunized with either PPS14 or PPS14-OVA, depletion of endogenous complement at the time of primary immunization by treatment with cobra venom factor (CVF) diminished serum anti-PPS14 concentrations after primary immunization but enhanced antibody responses after secondary immunization. The secondary immunoglobulin G (IgG) anti-PPS14 antibody response after immunization with PPS14-OVA was especially enhanced by complement depletion, was observed at doses as low as 0.2 μg of antigen, and was maximal when CVF was administered within 2 days of immunization. The avidity and opsonophagocytic functions of IgG anti-PPS14 antibodies were comparable in mice immunized with PPS14-OVA with or without complement depletion. Serum anti-PPS14 antibody concentrations were near normal, and the enhancing effects of CVF treatment on the secondary anti-PPS14 antibody response were also apparent in splenectomized mice immunized with PPS14-OVA. These results demonstrate that complement activation can have distinct effects on the primary and secondary antibody responses to a T-cell-independent type 2 antigen, either unmodified or conjugated to a T-cell-dependent protein carrier. These differences should be taken into consideration when using complement to modulate the immune response to vaccines.
Downregulation of Mitogen-Activated Protein Kinases by theBordetella bronchisepticaType III Secretion System Leads to Attenuated Nonclassical Macrophage Activation
Authors: Reissinger Annette , Skinner Jason A. , Yuk Ming H. 
Published: December 2004

ABSTRACTBordetella bronchisepticautilizes a type III secretion system (TTSS) to establish a persistent infection of the murine respiratory tract. Previous studies have shown that theBordetellaTTSS mediated cytotoxicity in different cell types, inhibition of NF-κB in epithelial cells, and differentiation of dendritic cells into a semimature state. Here we demonstrate modulation of mitogen-activated protein kinase (MAPK) signaling pathways and altered cytokine production in macrophages and dendritic cells by theBordetellaTTSS. In macrophages, the MAPKs ERK and p38 were downregulated. This resulted in attenuated production of interleukin- (IL-)6 and IL-10. In contrast, the Th-1-polarizing cytokine IL-12 was produced at very low levels and remained unmodulated by theBordetellaTTSS. In dendritic cells, ERK was transiently activated, but this failed to alter cytokine profiles. These results suggest that theBordetellaTTSS modulates antigen-presenting cells in a cell type-specific manner and the secretion of high levels of IL-6 and IL-10 by macrophages might be important for pathogen clearance.
Dendritic Cells Activated with Products Released by Schistosome Larvae Drive Th2-Type Immune Responses, Which Can Be Inhibited by Manipulation of CD40 Costimulation
Authors: Jenkins Stephen John , Mountford Adrian Paul 
Published: December 2004

ABSTRACT

The early immune events in response to infective larvae of the parasitic helminth
Schistosoma mansoni
are poorly understood, but here for the first time we report on the potential of products released by schistosome larvae (material released in the first 3 h after transformation [0-3hRP]) to stimulate the maturation of dendritic cells (DC) and alter their T-cell-polarizing function. This was performed in comparison with lipopolysaccharide (LPS) and zymosan A, which classically activate DC to prime for Th1- and Th2-type responses, respectively. In our study, immature bone marrow-derived DC stimulated in vitro with 0-3hRP exhibited up-regulated expression of major histocompatibility complex class II, CD40, and CD86 and increased production of interleukin 12p40 (IL-12p40) and IL-6, albeit at lower levels than in response to LPS or zymosan A. Using an in vitro ovalbumin peptide-restricted priming assay, DC matured with 0-3hRP exhibited a potent capacity to drive Th2 polarization of CD4
+
cells from DO11.10 transgenic mice. This was characterized by increased IL-4 production (but not gamma interferon) of a magnitude similar to that primed by DC matured with zymosan A. Inoculation of DO11.10 mice with 0-3hRP-activated DC pulsed with ovalbumin peptide also led to the development of a Th2-type polarized response in the skin-draining lymph nodes and spleen. However, ligation of CD40 on DC by anti-CD40 antibody treatment reversed the ability of 0-3hRP-activated DC to prime for Th2-type responses and instead caused the induction of a more Th1-type response.
Allele Specificity of Naturally Acquired Antibody Responses against
Plasmodium falciparum
Apical Membrane Antigen 1
Authors: Cortés Alfred , Mellombo Mata , Masciantonio Rosella , Murphy Vince J. , Reeder John C. , Anders Robin F. 
Published: December 2004

ABSTRACT

Antibody responses against proteins located on the surface or in the apical organelles of merozoites are presumed to be important components of naturally acquired protective immune responses against the malaria parasite
Plasmodium falciparum
. However, many merozoite antigens are highly polymorphic, and antibodies induced against one particular allelic form might not be effective in controlling growth of parasites expressing alternative forms. The apical membrane antigen 1 (AMA1) is a polymorphic merozoite protein that is a target of naturally acquired invasion-inhibitory antibodies and is a leading asexual-stage vaccine candidate. We characterized the antibody responses against AMA1 in 262 individuals from Papua New Guinea exposed to malaria by using different allelic forms of the full AMA1 ectodomain and some individual subdomains. The majority of individuals had very high levels of antibodies against AMA1. The prevalence and titer of these antibodies increased with age. Although antibodies against conserved regions of the molecule were predominant in the majority of individuals, most plasma samples also contained antibodies directed against polymorphic regions of the antigen. In a few individuals, predominantly from younger age groups, the majority of antibodies against AMA1 were directed against polymorphic epitopes. The D10 allelic form of AMA1 apparently contains most if not all of the epitopes present in the other allelic forms tested, which might argue for its inclusion in future AMA1-based vaccines to be tested. Some important epitopes in AMA1 involved residues located in domain II or III but depended on more than one domain.
Testosterone Suppresses Protective Responses of the Liver to Blood-Stage Malaria
Authors: Krücken Jürgen , Dkhil Mohamed A. , Braun Juliane V. , Schroetel Regina M. U. , El-Khadragy Manal , Carmeliet Peter , Mossmann Horst , Wunderlich Frank 
Published: December 2004

ABSTRACT

Testosterone induces a lethal outcome in otherwise self-healing blood-stage malaria caused by
Plasmodium chabaudi
. Here, we examine possible testosterone effects on the antimalaria effectors spleen and liver in female C57BL/6 mice. Self-healing malaria activates gating mechanisms in the spleen and liver that lead to a dramatic reduction in trapping activity, as measured by quantifying the uptake of 3-μm-diameter fluorescent polystyrol particles. However, testosterone delays malaria-induced closing of the liver, but not the spleen. Coincidently, testosterone causes an ∼3- to 28-fold depression of the mRNA levels of nine malaria-responsive genes, out of 299 genes tested, only in the liver and not in the spleen, as shown by cDNA arrays and Northern blotting. Among these are the genes encoding plasminogen activator inhibitor (PAI1) and hydroxysteroid sulfotransferase (STA2). STA2, which detoxifies bile acids, is suppressed 10-fold by malaria and an additional 28-fold by testosterone, suggesting a severe perturbation of bile acid metabolism. PAI1 is protective against malaria, since disruption of the PAI1 gene results in partial loss of the ability to control the course of
P. chabaudi
infections. Collectively, our data indicate that the liver rather than the spleen is a major target organ for testosterone-mediated suppression of resistance against blood-stage malaria.
CCL20/Macrophage Inflammatory Protein 3α and Tumor Necrosis Factor Alpha Production by Primary Uterine Epithelial Cells in Response to Treatment with Lipopolysaccharide or Pam3Cys
Authors: Crane-Godreau Mardi A. , Wira Charles R. 
Published: December 2004

ABSTRACTHaving previously shown that CCL20/macrophage inflammatory protein 3α and tumor necrosis factor alpha (TNF-α) are released by polarized primary rat uterine epithelial cells (UEC) in response toEscherichia colibut not toLactobacillus rhamnosus, we sought to determine if epithelial cells are responsive to pathogen-associated molecular patterns (PAMP), including lipopolysaccharide (LPS), lipoteichoic acid (LTA), and Pam3Cys, a bacterial lipoprotein analog. Epithelial cells were grown to confluence on Nunc cell culture inserts prior to apical treatment with PAMPs. In response to LPS, LTA, and Pam3Cys (EMC Microcollection GmbH, Tübingen, Germany), CCL20 levels increased (4- to 10-fold) while PAMPs caused increased TNF-α (1- to 4-fold) in the medium collected after 24 h of incubation. Both apical and basolateral secretion of CCL20 and TNF-α increased in response to PAMPs, but treatments had no effect on cell viability and integrity, as measured by transepithelial resistance. Time course studies of CCL20 and TNF-α release in response to Pam3Cys and LPS indicated that CCL20 release peaked between 2 and 4 h after treatment, whereas TNF-α release was gradual over the length of the incubation. Freeze-thaw and cell lysis experiments, along with actinomycin D studies, suggested that CCL20 and TNF-α are synthesized in response to PAMP stimulation. Taken together, these studies demonstrate thatE. coliand selected PAMPs have direct effects on the production of CCL20 and TNF-α without affecting cell integrity. Since CCL20 is known to be both chemotactic and antimicrobial, the increase in apical and basolateral release by UEC in response to PAMPs suggests a new mechanism of innate immune protection in the female reproductive tract.
Differences in Patterns of Infection and Inflammation for Corticosteroid Treatment and Chemotherapy in Experimental Invasive Pulmonary Aspergillosis
Authors: Balloy Viviane , Huerre Michel , Latgé Jean-Paul , Chignard Michel 
Published: December 2004

ABSTRACTAspergillus fumigatuscauses invasive pulmonary aspergillosis (IPA). This disease is one of the most life-threatening opportunistic infections in immunocompromised patients. The type of immunosuppressive regimen under which IPA occurs has rarely been investigated. In this study, we evaluated various parameters of the innate immune response during the progression of murine IPA induced by the intratracheal administration ofA. fumigatusconidia as a function of two immunosuppressive treatments: a corticosteroid and a chemotherapeutic agent. We compared host responses various times after infection in terms of survival, pulmonary production of pro- and anti-inflammatory cytokines, cellular trafficking in the airways, lung injury, respiratory distress, and fungal development. We found that IPA pathogenesis involved predominantly fungal development in mice treated by chemotherapy and an adverse host response in mice treated with a corticosteroid. These previously unrecognized differences should be taken into account in evaluations of the pathogenesis of IPA in animal models.
Virulent
Shigella flexneri
Causes Damage to Mitochondria and Triggers Necrosis in Infected Human Monocyte-Derived Macrophages
Authors: Koterski James F. , Nahvi Massoumeh , Venkatesan Malabi M. , Haimovich Beatrice 
Published: December 2004

ABSTRACT

Shigella flexneri
is a gram-negative bacterium that causes bacillary dysentery in humans that is characterized by an acute inflammatory response of the colon. The fate of phagocytes that are infected in vitro with virulent
Shigella
has been the subject of some investigation and debate. In this study we found that virulent
Shigella
caused a rapid increase in the cell membrane permeability of infected human monocyte-derived macrophages (HMDM) but not in the cell membrane permeability of monocytes, as demonstrated by the uptake of fluorescent vital dyes. Within 2 h of infection, 59% ± 6% of the HMDM and ≤4% of the monocytes were stained with propidium iodide. Treatment of the cells with the inhibitors of caspases YVAD and zVAD, the antioxidants
N
-acetyl-
l
-cysteine and butylated hydroxyanisole, or an inhibitor of NADPH oxidase, diphenyleniodonium, did not alter the infection outcome. Importantly, we found that virulent
Shigella
caused a rapid drop in the ATP level to about 50% in infected HMDM. Furthermore, using a combination of fluorescent vital dyes and mitochondrial membrane potential-sensitive dyes, we observed that cells that exhibited a permeable cell membrane were not stained by the mitochondrion-specific dyes, indicating that the mitochondrial membrane potential was lost in these cells. We also observed infected cells that were not stained with either type of dye, indicating that the loss of the mitochondrial membrane potential preceded the increase in cell membrane permeability. Taken together, our studies showed that virulent
Shigella flexneri
targets the host cell mitochondria for destruction. This activity may account for the necrotic cell death precipitated by these pathogens.