bluuebunny/crossref_metadata_2025_split huggingface dataset:
PspK of Streptococcus pneumoniae Increases Adherence to Epithelial Cells and Enhances Nasopharyngeal Colonization
Authors: Keller L. E. , Jones C. V. , Thornton J. A. , Sanders M. E. , Swiatlo E. , Nahm M. H. , Park I. H. , McDaniel L. S. 
Published: November 2012

ABSTRACT

Streptococcus pneumoniae
(the pneumococcus) colonizes the human nasopharynx and can cause invasive disease aided by the pneumococcal capsule. Group II nontypeable
S. pneumoniae
(NTSp) lacks a polysaccharide capsule, and a subgroup of NTSp carriage isolates has been found to have a novel gene, pneumococcal surface protein K (
pspK
), which replaces the capsule locus. A recent rise in the number of NTSp isolates colonizing the human nasopharynx has been observed, but the colonization factors of NTSp have not been well studied. PspK has been shown to play a role in mouse colonization. We therefore examined PspK-mediated immune evasion along with adherence to host cells and colonization. PspK bound human secretory immunoglobulin A (sIgA) but not the complement regulator factor H and did not decrease C3b deposition on the pneumococcal surface. PspK increased binding of pneumococci to epithelial cells and enhanced pneumococcal colonization independently of the genetic background. Understanding how NTSp colonizes and survives within the nasopharynx is important due to the increase in NTSp carriage. Our data suggest that PspK may aid in the persistence of NTSp within the nasopharynx but is not involved in invasion.
Effect of Angiotensin II Receptor Blocker on Experimental Periodontitis in a Mouse Model of Marfan Syndrome
Authors: Suda Naoto , Moriyama Keiji , Ganburged Ganjargal 
Published: November 2012

ABSTRACT

Marfan syndrome is an autosomal dominant disease characterized by aneurysm and dilatation of the aortic root, tall stature, and ectopia lentis. These manifestations reflect excessive signaling of transforming growth factor beta (TGF-β). Moreover, cases are frequently associated with severe periodontitis, which is a chronic inflammation of the gingiva, periodontal ligament, and alveolar bone. Recently, angiotensin II receptor blockers (ARBs) were discovered to be an effective drug class that can prevent aortic aneurysm and dilation in Marfan syndrome by inhibiting TGF-β signaling. To investigate the effect of ARB on the progression of periodontitis, the application of a potent ARB, telmisartan, was examined in a mouse model of Marfan syndrome (MgΔ). Six-week-old male heterozygous MgΔ and wild-type mice were challenged with
Porphyromonas gingivalis
, which causes chronic periodontitis, with and without telmisartan application. After infection, alveolar bone resorption was measured by micro-computed tomography (μCT), and inflammatory cytokine levels were examined. Infection of
Porphyromonas gingivalis
induced alveolar bone resorption in both MgΔ and wild-type mice. The amount of resorption was significantly larger in the former than the latter. Immunoarray and enzyme-linked immunosorbent assay (ELISA) analyses demonstrated that interleukin-17 (IL-17) and tumor necrosis factor alpha (TNF-α) levels were significantly higher in infected MgΔ mice than infected wild-type mice. Telmisartan treatment significantly suppressed the alveolar bone resorption of infected MgΔ mice. Telmisartan also significantly decreased levels of TGF-β, IL-17, and TNF-α in infected MgΔ mice to levels seen in infected wild-type mice. This study suggests that ARB can prevent the severe periodontitis frequently seen in Marfan syndrome.
Transcriptional Modulation of Enterotoxigenic Escherichia coli Virulence Genes in Response to Epithelial Cell Interactions
Authors: Kansal Rita , Rasko David A. , Sahl Jason W. , Munson George P. , Roy Koushik , Luo Qingwei , Sheikh Alaullah , Kuhne Kurt J. , Fleckenstein James M. 
Published: November 2012

ABSTRACTEnterotoxigenicEscherichia coli(ETEC) strains are a leading cause of morbidity and mortality due to diarrheal illness in developing countries. There is currently no effective vaccine against these important pathogens. Because genes modulated by pathogen-host interactions potentially encode putative vaccine targets, we investigated changes in gene expression and surface morphology of ETEC upon interaction with intestinal epithelial cellsin vitro. Pan-genome microarrays, quantitative reverse transcriptase PCR (qRT-PCR), and transcriptional reporter fusions of selected promoters were used to study changes in ETEC transcriptomes. Flow cytometry, immunofluorescence microscopy, and scanning electron microscopy were used to investigate alterations in surface antigen expression and morphology following pathogen-host interactions. Following host cell contact, genes for motility, adhesion, toxin production, immunodominant peptides, and key regulatory molecules, including cyclic AMP (cAMP) receptor protein (CRP) and c-di-GMP, were substantially modulated. These changes were accompanied by visible changes in both ETEC architecture and the expression of surface antigens, including a novel highly conserved adhesin molecule, EaeH. The studies reported here suggest that pathogen-host interactions are finely orchestrated by ETEC and are characterized by coordinated responses involving the sequential deployment of multiple virulence molecules. Elucidation of the molecular details of these interactions could highlight novel strategies for development of vaccines for these important pathogens.
Francisella tularensis Live Vaccine Strain Folate Metabolism and Pseudouridine Synthase Gene Mutants Modulate Macrophage Caspase-1 Activation
Authors: Ulland Tyler K. , Janowski Ann M. , Buchan Blake W. , Faron Matthew , Cassel Suzanne L. , Jones Bradley D. , Sutterwala Fayyaz S. 
Published: November 2012

ABSTRACTFrancisella tularensisis a Gram-negative bacterium and the causative agent of the disease tularemia. Escape ofF. tularensisfrom the phagosome into the cytosol of the macrophage triggers the activation of the AIM2 inflammasome through a mechanism that is not well understood. Activation of the AIM2 inflammasome results in autocatalytic cleavage of caspase-1, resulting in the processing and secretion of interleukin-1β (IL-1β) and IL-18, which play a crucial role in innate immune responses toF. tularensis. We have identified the5-formyltetrahydrofolate cycloligasegene (FTL_0724) as being important forF. tularensislive vaccine strain (LVS) virulence. Infection of micein vivowith aF. tularensisLVSFTL_0724mutant resulted in diminished mortality compared to infection of mice with wild-type LVS. TheFTL_0724mutant also induced increased inflammasome-dependent IL-1β and IL-18 secretion and cytotoxicity in macrophagesin vitro. In contrast, infection of macrophages with aF. tularensisLVSrluD pseudouridine synthase(FTL_0699) mutant resulted in diminished IL-1β and IL-18 secretion from macrophagesin vitrocompared to infection of macrophages with wild-type LVS. In addition, theFTL_0699mutant was not attenuatedin vivo. These findings further illustrate thatF. tularensisLVS possesses numerous genes that influence its ability to activate the inflammasome, which is a key host strategy to control infection with this pathogenin vivo.
Natural Competence Promotes Helicobacter pylori Chronic Infection
Authors: Dorer Marion S. , Cohen Ilana E. , Sessler Tate H. , Fero Jutta , Salama Nina R. 
Published: November 2012

ABSTRACT

Animal models are important tools for studies of human disease, but developing these models is a particular challenge with regard to organisms with restricted host ranges, such as the human stomach pathogen
Helicobacter pylori
. In most cases,
H. pylori
infects the stomach for many decades before symptoms appear, distinguishing it from many bacterial pathogens that cause acute infection. To model chronic infection in the mouse, a human clinical isolate was selected for its ability to survive for 2 months in the mouse stomach, and the resulting strain, MSD132, colonized the mouse stomach for at least 28 weeks. During selection, the
cagY
component of the Cag type IV secretion system was mutated, disrupting a key interaction with host cells. Increases in both bacterial persistence and bacterial burden occurred prior to this mutation, and a mixed population of
cagY
+
and
cagY
mutant cells was isolated from a single mouse, suggesting that mutations accumulate during selection and that factors in addition to the Cag apparatus are important for murine adaptation. Diversity in both alleles and genes is common in
H. pylori
strains, and natural competence mediates a high rate of interstrain genetic exchange. Mutations of the Com apparatus, a membrane DNA transporter, and DprA, a cytosolic competence factor, resulted in reduced persistence, although initial colonization was normal. Thus, exchange of DNA between genetically heterogeneous
H. pylori
strains may improve chronic colonization. The strains and methods described here will be important tools for defining both the spectrum of mutations that promote murine adaptation and the genetic program of chronic infection.
Close Geographic Association of Human Neoehrlichiosis and Tick Populations Carrying “Candidatus Neoehrlichia mikurensis” in Eastern Switzerland
Authors: Maurer Florian P. , Keller Peter M. , Beuret Christian , Joha Cornelia , Achermann Yvonne , Gubler Jacques , Bircher Daniela , Karrer Urs , Fehr Jan , Zimmerli Lukas , Bloemberg Guido V. 
Published: November 2012

ABSTRACT

Neoehrlichiosis caused by “
Candidatus
Neoehrlichia mikurensis” is an emerging zoonotic disease. In total, six patients have been described in Europe, with the first case detected in 2007. In addition, seven patients from China were described in a report published in October 2012. In 2009, we diagnosed the first human case of “
Ca
. Neoehrlichia mikurensis” infection in the Zurich area (Switzerland). Here, we report two additional human cases from the same region, which were identified by broad-range 16S rRNA gene PCR. Both patients were immunocompromised and presented with similar clinical syndromes, including fever, malaise, and weight loss. A diagnostic multiplex real-time PCR was developed for specific detection of “
Ca
. Neoehrlichia mikurensis” infections. The assay is based on the signature sequence of a 280-bp fragment of the “
Ca
. Neoehrlichia mikurensis” 16S rRNA gene and incorporates a “
Ca
. Neoehrlichia mikurensis” species, a “
Ca
. Neoehrlichia” genus, and an
Anaplasmataceae
family probe for simultaneous screening. The analytical sensitivity was determined to be below five copies of the “
Ca
. Neoehrlichia mikurensis” 16S rRNA gene. Our results show that the assay is suitable for the direct detection of “
Ca
. Neoehrlichia mikurensis” DNA in clinical samples from, for example, blood and bone marrow. In addition, it allows for monitoring treatment response during antibiotic therapy. Using the same assay, DNA extracts from 1,916 ticks collected in four forests in close proximity to the patients' residences (<3 km) were screened. At all sampling sites, the minimal prevalence of “
Ca
. Neoehrlichia mikurensis” was between 3.5 to 8% in pools of either nymphs, males, or females, showing a strong geographic association between the three patients and the assumed vector.
Environmental Contamination by Carbapenem-Resistant Enterobacteriaceae
Authors: Lerner A. , Adler A. , Abu-Hanna J. , Meitus I. , Navon-Venezia S. , Carmeli Y. 
Published: November 2012

ABSTRACT

In the last decade, the global emergence of carbapenem resistance in
Enterobacteriaceae
has posed great concern to public health. Data concerning the role of environmental contamination in the dissemination of carbapenem-resistant
Enterobacteriaceae
(CRE) are currently lacking. Here, we aimed to examine the extent of CRE contamination in various sites in the immediate surroundings of CRE carriers and to assess the effects of sampling time and cleaning regimens on the recovery rate. We evaluated the performance of two sampling methods, CHROMAgar KPC contact plate and eSwab, for the detection of environmental CRE. eSwab was followed either by direct plating or by broth enrichment. First, 14 sites in the close vicinity of the carrier were evaluated for environmental contamination, and 5, which were found to be contaminated, were further studied. The environmental contamination decreased with distance from the patient; the bed area was the most contaminated site. Additionally, we found that the sampling time and the cleaning regimen were critical factors affecting the prevalence of environmental CRE contamination. We found that the CHROMAgar KPC contact plate method was a more effective technique for detecting environmental CRE than were eSwab-based methods. In summary, our study demonstrated that the vicinity of patients colonized with CRE is often contaminated by these organisms. Using selective contact plates to detect environmental contamination may guide cleaning efficacy and assist with outbreak investigation in an effort to limit the spread of CRE.
Identification by Full-Genome Analysis of a Bovine Rotavirus Transmitted Directly to and Causing Diarrhea in a Human Child
Authors: Doan Yen Hai , Nakagomi Toyoko , Aboudy Yair , Silberstein Ilana , Behar-Novat Esther , Nakagomi Osamu , Shulman Lester M. 
Published: November 2012

ABSTRACT
The genome of rotaviruses consists of 11 segments of double-stranded RNA, and each genome segment has multiple genotypes. Thus, the genotype constellation of an isolate is often indicative of its host species. Albeit rarely, interspecies transmission occurs either by virions with nonreassorted or reassorted genomic segments. A rotavirus with the G6P[1] genotype, Ro8059, was isolated from the stool of a 1-year-old child during routine characterization of diarrheal specimens from a sentinel clinic in Israel in 1995. Since genotype G6P[1] is generally associated with bovine rotaviruses, and the child developed diarrhea within days of his first contact with calves at an urban farm, the aim of this study was to characterize the whole genomic constellation of Ro8059 and four G6P[1] bovine strains, BRV101, BRV105, BRV106, and CR231/39, by RNA-RNA hybridization and full genome sequencing to determine whether some or all of the segments were of bovine origin. The genome constellations of all four bovine G6P[1] strains were G6-P[1]-I2-R2-C2-M2-A3-N2-T6-E2-H3 for VP7-VP4-VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5, respectively. Ro8059 shared the same genotype constellation with these bovine strains, with high nucleotide sequence identities (95.84 to 100%) for each of the 11 segments indicating that Ro8059 represented a direct interspecies whole-genome transmission of a nonreassorted rotavirus from a calf to a human infant. We conclude that this was the earliest example with a complete epidemiological link in which an entirely bovine rotavirus directly infected a human child and caused a symptomatic diarrheal illness. Thus, not all bovine rotaviruses are always naturally attenuated to the human host.
Multilocus Sequence Typing for Characterization of Staphylococcus pseudintermedius
Authors: Solyman S. M. , Black C. C. , Duim B. , Perreten V. , van Duijkeren E. , Wagenaar J. A. , Eberlein L. C. , Sadeghi L. N. , Videla R. , Bemis D. A. , Kania S. A. 
Published: November 2012

ABSTRACT

Staphylococcus pseudintermedius
is an opportunistic pathogen in dogs. Four housekeeping genes with allelic polymorphisms were identified and used to develop an expanded multilocus sequence typing (MLST) scheme. The new seven-locus technique shows
S. pseudintermedius
to have greater genetic diversity than previous methods and discriminates more isolates based upon host origin.
The Herpes Simplex Virus 1 Us11 Protein Inhibits Autophagy through Its Interaction with the Protein Kinase PKR
Authors: Lussignol Marion , Queval Christophe , Bernet-Camard Marie-Françoise , Cotte-Laffitte Jacqueline , Beau Isabelle , Codogno Patrice , Esclatine Audrey 
Published: November 2012

ABSTRACT
Autophagy is now known to be an essential component of host innate and adaptive immunity. Several herpesviruses have developed various strategies to evade this antiviral host defense. Herpes simplex virus 1 (HSV-1) blocks autophagy in fibroblasts and in neurons, and the ICP34.5 protein is important for the resistance of HSV-1 to autophagy because of its interaction with the autophagy machinery protein Beclin 1. ICP34.5 also counteracts the shutoff of protein synthesis mediated by the double-stranded RNA (dsRNA)-dependent protein kinase PKR by inhibiting phosphorylation of the eukaryotic translation initiation factor 2α (eIF2α) in the PKR/eIF2α signaling pathway. Us11 is a late gene product of HSV-1, which is also able to preclude the host shutoff by direct inhibition of PKR. In the present study, we unveil a previously uncharacterized function of Us11 by demonstrating its antiautophagic activity. We show that the expression of Us11 is able to block autophagy and autophagosome formation in both HeLa cells and fibroblasts. Furthermore, immediate-early expression of Us11 by an ICP34.5 deletion mutant virus is sufficient to render the cells resistant to PKR-induced and virus-induced autophagy. PKR expression and the PKR binding domain of Us11 are required for the antiautophagic activity of Us11. However, unlike ICP34.5, Us11 did not interact with Beclin 1. We suggest that the inhibition of autophagy observed in cells infected with HSV-1 results from the activity of not only ICP34.5 on Beclin 1 but also Us11 by direct interaction with PKR.
Rotavirus Viroplasm Proteins Interact with the Cellular SUMOylation System: Implications for Viroplasm-Like Structure Formation
Authors: Campagna Michela , Marcos-Villar Laura , Arnoldi Francesca , de la Cruz-Herrera Carlos F. , Gallego Pedro , González-Santamaría José , González Dolores , Lopitz-Otsoa Fernando , Rodriguez Manuel S. , Burrone Oscar R. , Rivas Carmen 
Published: November 2012

ABSTRACT

Posttranslational modification by SUMO provides functional flexibility to target proteins. Viruses interact extensively with the cellular SUMO modification system in order to improve their replication, and there are numerous examples of viral proteins that are SUMOylated. However, thus far the relevance of SUMOylation for rotavirus replication remains unexplored. In this study, we report that SUMOylation positively regulates rotavirus replication and viral protein production. We show that SUMO can be covalently conjugated to the viroplasm proteins VP1, VP2, NSP2, VP6, and NSP5. In addition, VP1, VP2, and NSP2 can also interact with SUMO in a noncovalent manner. We observed that an NSP5 SUMOylation mutant protein retains most of its activities, such as its interaction with VP1 and NSP2, the formation of viroplasm-like structures after the coexpression with NSP2, and the ability to complement in
trans
the lack of NSP5 in infected cells. However, this mutant is characterized by a high degree of phosphorylation and is impaired in the formation of viroplasm-like structures when coexpressed with VP2. These results reveal for the first time a positive role for SUMO modification in rotavirus replication, describe the SUMOylation of several viroplasm resident rotavirus proteins, and demonstrate a requirement for NSP5 SUMOylation in the production of viroplasm-like structures.
Inefficient Vaginal Transmission of Tenofovir-Resistant HIV-1
Authors: Chateau Morgan , Swanson Michael D. , Garcia J. Victor 
Published: November 2012

ABSTRACTTransmission of drug-resistant HIV has been postulated to be a threat to current first-line antiretroviral therapy (ART) regimens and the efficacy of several antiretroviral-based preexposure prophylaxis (PrEP) strategies being tested. Here we evaluated the effect of the common tenofovir (TFV) resistance mutation K65R on vaginal HIV transmission. Our results demonstrate that despite no overt loss of overall replication competencein vivo, this mutation results in significantly reduced mucosal transmission. When transmitted, the mutant virus eventually reverted to the wild type in 2 of 3 animals examined.
Macropinocytosis-Like HIV-1 Internalization in Macrophages Is CCR5 Dependent and Leads to Efficient but Delayed Degradation in Endosomal Compartments
Authors: Gobeil Lise-Andrée , Lodge Robert , Tremblay Michel J. 
Published: November 2012

ABSTRACT
HIV-1 endocytosis by a macropinocytosis-like mechanism has been shown to lead to productive infection in macrophages. However, little is known of this pathway. In this study, we examined HIV-1 endocytosis using biochemical approaches and imaging techniques in order to better understand the mechanisms that allow for productive infection of these cells via the endosomal pathway. We show here that this macropinocytosis-like mechanism is not the sole pathway involved in HIV-1 endocytosis in macrophages. However, this pathway specifically requires CCR5 engagement at the cell surface, which in turn suggests that the virus and its coreceptor are present in the endosomal environment simultaneously. Furthermore, although we observed efficient viral degradation following endocytosis, analyses of HIV-1 transport through the endolysosomal pathway revealed that viral degradation is delayed following endosomal internalization, possibly allowing the virus to complete its fusion.
The Viral Interferon Regulatory Factors of Kaposi's Sarcoma-Associated Herpesvirus Differ in Their Inhibition of Interferon Activation Mediated by Toll-Like Receptor 3
Authors: Jacobs Sarah R. , Gregory Sean M. , West John A. , Wollish Amy C. , Bennett Christopher L. , Blackbourn David J. , Heise Mark T. , Damania Blossom 
Published: November 2012

ABSTRACT
Kaposi's sarcoma-associated herpesvirus (KSHV) infection is correlated with three human malignancies and can establish lifelong latent infection in multiple cell types within its human host. In order to establish and maintain infection, KSHV utilizes multiple mechanisms to evade the host immune response. One such mechanism is the expression of a family of genes with homology to cellular interferon (IFN) regulatory factors (IRFs), known as viral IRFs (vIRFs). We demonstrate here that KSHV vIRF1, -2, and -3 have a differential ability to block type I interferon signaling mediated by Toll-like receptor 3 (TLR3), a receptor we have previously shown to be activated upon KSHV infection. vIRF1, -2, and -3 inhibited TLR3-driven activation of IFN transcription reporters. However, only vIRF1 and vIRF2 inhibited increases in both IFN-β message and protein levels following TLR3 activation. The expression of vIRF1 and vIRF2 also allowed for increased replication of a virus known to activate TLR3 signaling. Furthermore, vIRF1 and vIRF2 may block TLR3-mediated signaling via different mechanisms. Altogether, this report indicates that vIRFs are able to block IFN mediated by TLRs but that each vIRF has a unique function and mechanism for blocking antiviral IFN responses.
Fixation of Emerging Interviral Recombinants in Cucumber Mosaic Virus Populations
Authors: Pita Justin S. , Roossinck Marilyn J. 
Published: November 2012

ABSTRACT

Interstrain recombinants were observed in the progenies of the
Cucumber mosaic virus
(CMV) reassortant L
1
L
2
F
3
containing RNAs 1 and 2 from LS-CMV and RNA 3 from Fny-CMV. We characterized these recombinants, and we found that their fixation was controlled by the nature of the replicating RNAs 1 and 2. We demonstrate that the 2b gene partially affects this fixation process, but only in the context of homologous RNAs 1 and 2.