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safety and immunogenicity of a shigella flexneri 2a invaplex 50 intranasal vaccine in adult volunteers.shigellosis is a leading cause of diarrhea worldwide prompting vaccine development. the shigella flexneri invaplex 50 is a macromolecular complex containing ipab, ipac, and lps, formulated from an aqueous extract of virulent shigella delivered via nasal administration. preclinical vaccine testing demonstrated safety, immunogenicity and efficacy. an open-label dose-escalating phase 1 study evaluated a 3-dose (2-week intervals) regimen via nasal pipette delivery. thirty-two subjects were enrolled ...201020619378
evidence for alternative quaternary structure in a bacterial type iii secretion system chaperone.type iii secretion systems are a common virulence mechanism in many gram-negative bacterial pathogens. these systems use a nanomachine resembling a molecular needle and syringe to provide an energized conduit for the translocation of effector proteins from the bacterial cytoplasm to the host cell cytoplasm for the benefit of the pathogen. prior to translocation specialized chaperones maintain proper effector protein conformation. the class ii chaperone, invasion plasmid gene (ipg) c, stabilizes ...201020633281
the omptins of yersinia pestis and salmonella enterica cleave the reactive center loop of plasminogen activator inhibitor 1.plasminogen activator inhibitor 1 (pai-1) is a serine protease inhibitor (serpin) and a key molecule that regulates fibrinolysis by inactivating human plasminogen activators. here we show that two important human pathogens, the plague bacterium yersinia pestis and the enteropathogen salmonella enterica serovar typhimurium, inactivate pai-1 by cleaving the r346-m347 bait peptide bond in the reactive center loop. no cleavage of pai-1 was detected with yersinia pseudotuberculosis, an oral/fecal pat ...201020639337
photodynamic antimicrobial chemotherapy by liposome-encapsulated water-soluble photosensitizers.photodynamic antimicrobial chemotherapy is an alternative method for killing bacterial cells in view of the increasing problem of multi-antibiotic resistance. we examined the effect of three water-soluble photosensitizers (phs): methylene blue (mb), neutral red (nr) and rose bengal (rb) on gram-positive and gram-negative bacteria. we compared the efficacy of phs in their free form and encapsulated in liposomal formulations against various bacterial strains, and determined conditions for the effe ...201020644595
[structure of the oligosaccharide region (core) of the lipopolysaccharides of shigella flexneri types 2a and 5b].the full structure of the lipopolysaccharide core of bacteria shigella flexneri types 2a and 5b, the causative agents of bacillary dysentery (shigellosis), was established by chemical methods, high-resolution electrospray ionization mass spectrometry, and two-dimensional nmr spectroscopy. the structure of the o-antigen repeating unit and the configuration and position of the linkage between the o-antigen and the core were determined in the lipopolysaccharide of s. flexneri type 2a.201020644600
enteropathogenic escherichia coli, samonella, shigella and yersinia: cellular aspects of host-bacteria interactions in enteric diseases.abstract: a successful infection of the human intestine by enteropathogenic bacteria depends on the ability of bacteria to attach and colonize the intestinal epithelium and, in some cases, to invade the host cell, survive intracellularly and disseminate from cell to cell. to accomplish these processes bacteria have evolved an arsenal of molecules that are mostly secreted by dedicated type iii secretion systems, and that interact with the host, subverting normal cellular functions. here we overvi ...201020649986
in silico characterization of shikimate kinase of shigella flexneri: a potential drug target.shigella flexneri is a major pathogen responsible for shigellosis causing massive morbidity among young population and imposes huge socio-economic burden. in this study, shikimate kinase (sk) from s. flexneri was characterized in silico and disordered regions were predicted. motifs and domains were calculated using computational tools. a three dimensional model of shikimate kinase of s.flexneri was constructed using shikimate kinase of e.coli (pdbid: 1kag_a) as template by comparative modeling a ...201020658341
facile glycosylation strategy with two-stage activation of allyl glycosyl donors. application to concise synthesis of shigella flexneri serotype y o-antigen.a practical, useful glycosylation method employing only allyl glycoside building blocks has been developed. the donor's glycosylation reactivity is turned on via isomerization of its anomeric allyl protecting group into the corresponding prop-1-enyl moiety. subsequent chemoselective activation with nis/tfoh achieves high yields in glycosidic bond construction at room temperature. the efficacy and efficiency of this approach in carbohydrate synthesis is demonstrated in the concise synthesis of th ...201020683518
plasmid-mediated streptomycin and sulfamethoxazole resistance in shigella flexneri 3a.shigellosis is a major cause of diarrhoea-related morbidity and mortality, especially in children in developing countries such as india. recently, it was estimated that 91 million individuals worldwide contract shigellosis each year. the emergence and dissemination of multidrug-resistant strains of shigella is now an emerging global health problem. during the past two decades, much attention was given to re-evaluation of treatment recommendations. in the present study, we investigated a clinical ...201020685089
hemolysin e (hlye, clya, shea) and related toxins.certain strains of escherichia coli, salmonella enterica and shigella flexneri produce a pore-forming toxin hemolysin e (hlye), also known as cytolysin a (clya) and silent hemolysin, locus a (shea). hlye lyses erythrocytes and mammalian cells, forming transmembrane pores with a minimum internal diameter of-25 a. we review the current knowledge of hlye structure and function in its solution and pore forms, models for membrane insertion, its potential use in biotechnology applications and its rela ...201020687485
crystal structures of phd-doc, higa, and yeeu establish multiple evolutionary links between microbial growth-regulating toxin-antitoxin systems.bacterial toxin-antitoxin (ta) systems serve a variety of physiological functions including regulation of cell growth and maintenance of foreign genetic elements. sequence analyses suggest that ta families are linked by complex evolutionary relationships reflecting likely swapping of functional domains between different ta families. our crystal structures of phd-doc from bacteriophage p1, the higa antitoxin from escherichia coli cft073, and yeeu of the yeeuwv systems from e. coli k12 and shigell ...201020696400
pic, an autotransporter protein secreted by different pathogens in the enterobacteriaceae family, is a potent mucus secretagogue.a hallmark of enteroaggregative escherichia coli (eaec) infection is a formation of biofilm, which comprises a mucus layer with immersed bacteria in the intestines of patients. while studying the mucinolytic activity of pic in an in vivo system, rat ileal loops, we surprisingly found that eaec induced hypersecretion of mucus, which was accompanied by an increase in the number of mucus-containing goblet cells. interestingly, an isogenic pic mutant (eaec δpic) was unable to cause this mucus hypers ...201020696826
csra and cra influence shigella flexneri pathogenesis.shigella flexneri is a facultative intracellular pathogen that invades and disrupts the colonic epithelium. in order to thrive in the host, s. flexneri must adapt to environmental conditions in the gut and within the eukaryotic cytosol, including variability in the available carbon sources and other nutrients. we examined the roles of the carbon consumption regulators csra and cra in a cell culture model of s. flexneri virulence. csra is an activator of glycolysis and a repressor of gluconeogene ...201020713625
detection of airborne bacteria in a german turkey house by cultivation-based and molecular methods.today's large-scale poultry production with densely stocked and enclosed production buildings is often accompanied by very high concentrations of airborne microorganisms leading to a clear health hazard for employees working in such environments. depending on the expected exposure to microorganisms, work has to be performed under occupational safety conditions. in this study, turkey houses bioaerosols were investigated by cultivation-based and molecular methods in parallel to determine the conce ...201020720091
medicinal potions used against infectious bowel diseases in mayan traditional medicine.since one of the main health problems of the indigenous population are infectious bowel diseases, we decided to test mayan medicinal potions used to treat these conditions against some of the causal agents.201020728517
pad4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps.neutrophils trap and kill bacteria by forming highly decondensed chromatin structures, termed neutrophil extracellular traps (nets). we previously reported that histone hypercitrullination catalyzed by peptidylarginine deiminase 4 (pad4) correlates with chromatin decondensation during net formation. however, the role of pad4 in net-mediated bacterial trapping and killing has not been tested. here, we use pad4 knockout mice to show that pad4 is essential for net-mediated antibacterial function. u ...201020733033
[the evolution of the etiological structure of shigellosis]. 201020734730
an outbreak of shigellosis due to shigella flexneri serotype 3a in a prison in iran.on june 16 and 17, 2007, the medical clinic of a prison in isfahan, iran received multiple reports of gastrointestinal illness among prisoners. a cross-sectional study was therefore undertaken to determine the extent, causative agent and possible source of the outbreak.201020804308
a disposable immunosensor for shigella flexneri based on multiwalled carbon nanotube/sodium alginate composite electrode.a novel shigella flexneri immunosensor based on horseradish peroxidase-labeled antibodies to s. flexneri (hrp-anti-s. flexneri) immobilized by physical adsorption on the multiwalled carbon nanotube (mwcnt)/sodium alginate (sa) composite modified screen-printed electrode surface was successfully fabricated. in this strategy, mwcnt/sa biocomposite acted as the matrix to adsorb and immobilize hrp-anti-s. flexneri. the modified electrodes were characterized with an atomic force microscope and cyclic ...201120816661
serotypes and extended-spectrum β-lactamase types of clinical isolates of shigella spp. from the zhejiang province of china.to understand the distribution of the serotypes of shigella spp. and to investigate the drug-resistant genes of extended-spectrum β-lactamases (esbls) in shigella in zhejiang province, we have collected clinically isolated shigella isolates from 2 hospitals in zhejiang province during august to december of 2006. there are 11 shigella flexneri and 13 shigella sonnei isolates, respectively. among the 11 s. flexneri, 9 are serotype f4 and the remaining 2 are f1a and f2a. antimicrobial susceptibilit ...201121146721
antigen-specific iga b memory cell responses to shigella antigens elicited in volunteers immunized with live attenuated shigella flexneri 2a oral vaccine candidates.we studied the induction of antigen-specific iga memory b cells (b(m)) in volunteers who received live attenuated shigella flexneri 2a vaccines. subjects ingested a single oral dose of 10(7), 10(8) or 10(9) cfu of s. flexneri 2a with deletions in guaba (cvd 1204) or in guaba, set and sen (cvd 1208). antigen-specific serum and stool antibody responses to lps and ipa b were measured on days 0, 7, 14, 28 and 42. iga b(m) cells specific to lps, ipa b and total iga were assessed on days 0 and 28. we ...201121388888
a candidate approach implicates the secreted salmonella effector protein spvb in p-body disassembly.p-bodies are dynamic aggregates of rna and proteins involved in several post-transcriptional regulation processes. p-bodies have been shown to play important roles in regulating viral infection, whereas their interplay with bacterial pathogens, specifically intracellular bacteria that extensively manipulate host cell pathways, remains unknown. here, we report that salmonella infection induces p-body disassembly in a cell type-specific manner, and independently of previously characterized pathway ...201121390246
structural elucidation of the o-antigen of the shigella flexneri provisional serotype 88-893: structural and serological similarities with s. flexneri provisional serotype y394 (1c).the structure of the repeating unit of the o-antigen polysaccharide from shigella flexneri provisional serotype 88-893 has been determined. (1)h and (13)c nmr spectroscopy as well as 2d nmr experiments were employed to elucidate the structure. the carbohydrate part of the hexasaccharide repeating unit is identical to the previously elucidated structure of the o-polysaccharide from s. flexneri prov. serotype y394. the o-antigen of s. flexneri prov. serotype 88-893 carries 0.7 mol o-acetyl group p ...201121392735
shigella flexneri type iii secreted effector ospf reveals new crosstalks of proinflammatory signaling pathways during bacterial infection.shigella flexneri type iii secreted effector ospf harbors a phosphothreonine lyase activity that irreversibly dephosphorylates map kinases (mapks) p38 and erk in infected epithelial cells and thereby, dampens innate immunity. whereas this activity has been well characterized, the impact of ospf on other host signaling pathways that control inflammation was unknown. here we report that ospf potentiates the activation of the mapk jnk and the transcription factor nf-?b during s. flexneri infection. ...201121402152
synthesis and in vitro microbiological evaluation of novel diethyl 6,6'-(1,4-phenylene)bis(4-aryl-2-oxo-cyclohex-3-enecarboxylates).novel bis cyclohexenone ester derivatives 14-19 were synthesized and characterized by their spectral data. in vitro microbiological evaluations were carried out for all the novel compounds 14-19 against clinically isolated bacterial and fungal strains. compounds 15, 16, 18 against staphylococcus aureus, 14, 15 against ß-haemolytic streptococcus, 15, 19 against micrococcus luteus, 17, 18 against salmonella typhii, 14, 17 against shigella flexneri, 15 against escherichia coli, 16 against pseudomon ...201121417963
evaluation of antidiarrheal and in vitro antiprotozoal activities of extracts of leaves of alocasia indica.alocasia indica schott (araceae) is used in several regions of india, especially in rural communities, by traditional medicine practitioners to treat diarrhea. however, no scientific data are available to justify the traditional potentials of the plant species in gastrointestinal disorders.201121428863
vinculin activators target integrins from within the cell to increase melanoma sensitivity to chemotherapy.metastatic melanoma is an aggressive skin disease for which there are no effective therapies. emerging evidence indicates that melanomas can be sensitized to chemotherapy by increasing integrin function. current integrin therapies work by targeting the extracellular domain, resulting in complete gains or losses of integrin function that lead to mechanism-based toxicities. an attractive alternative approach is to target proteins, such as vinculin, that associate with the integrin cytoplasmic doma ...201121460181
behavior of salmonella typhimurium, staphylococcus aureus, listeria monocytogenes, and shigella flexneri and shigella sonnei during production of pulque, a traditional mexican beverage.pulque is a typical fermented alcoholic beverage of central mexico, produced from the nectar of maguey agave plants. production systems are largely artisanal, with inadequate hygiene conditions and exposure to multiple contamination sources. no data exist on pulque microbiological safety and the behavior of pathogenic microorganisms in agave nectar and pulque. an initial trial was done of the behavior of salmonella typhimurium, staphylococcus aureus, listeria monocytogenes, and shigella flexneri ...201121477472
an integrated approach for finding overlooked genes in shigella.the completion of numerous genome sequences introduced an era of whole-genome study. however, many genes are missed during genome annotation, including small rnas (srnas) and small open reading frames (sorfs). in order to improve genome annotation, we aimed to identify novel srnas and sorfs in shigella, the principal etiologic agents of bacillary dysentery.201121483688
the shigella flexneri type three secretion system effector ipgd inhibits t cell migration by manipulating host phosphoinositide metabolism.shigella, the gram-negative enteroinvasive bacterium that causes shigellosis, relies on its type iii secretion system (ttss) and injected effectors to modulate host cell functions. however, consequences of the interaction between shigella and lymphocytes have not been investigated. we show that shigella invades activated human cd4(+) t lymphocytes. invasion requires a functional ttss and results in inhibition of chemokine-induced t cell migration, an effect mediated by the ttss effector ipgd, a ...201121501826
enteric virulence associated protein vapc inhibits translation by cleavage of initiator trna.eukaryotic pin (pilt n-terminal) domain proteins are ribonucleases involved in quality control, metabolism and maturation of mrna and rrna. the majority of prokaryotic pin-domain proteins are encoded by the abundant vapbc toxin-antitoxin loci and inhibit translation by an unknown mechanism. here we show that enteric vapcs are site-specific endonucleases that cleave trna(fmet) in the anticodon stem-loop between nucleotides +38 and +39 in vivo and in vitro. consistently, vapc inhibited translation ...201121502523
evaluation of low-copy genetic targets for waterborne bacterial pathogen detection via qpcr.recent developments in water quality research have highlighted difficulties in accurately predicting the incidence of pathogens within freshwater based on the viability, culturability and metabolic activity of indicator organisms. qpcr-driven assays are candidates to replace standard culture-based methods, however, protocols suitable for routine use have yet to be sufficiently validated. the objective of this study was to evaluate five oligonucleotide primers sets (etir, sinv, exot, vs1 and ipah ...201121514618
a novel vinculin binding site of the ipaa invasin of shigella.internalization of shigella into host epithelial cells, where the bacteria replicates and spreads to neighboring cells, requires a type 3 secretion system (t3ss) effector coined ipaa. ipaa binds directly to and activates the cytoskeletal protein vinculin after injection in the host cell cytosol and heretofore this was thought to be directed by two amphipathic α-helical vinculin binding sites (vbs) found in the c-terminal tail domain of ipaa. here we report a third vbs, ipaa-vbs3, that is located ...201121525010
synthesis, characterization and biological studies of sulfonamide schiff's bases and some of their metal derivatives.a new series of schiff base ligands derived from sulfonamide and their metal(ii) complexes [cobalt(ii), copper(ii), nickel(ii) and zinc(ii)] have been synthesized and characterized. the nature of bonding and structure of all the synthesized compounds has been explored by physical, analytical and spectral data of the ligands and their metal(ii) complexes. the authors suggest that all the prepared complexes possess an octahedral geometry. the ligands and metal(ii) complexes have been screened for ...201121534864
rapid situation & response assessment of diarrhoea outbreak in a coastal district following tropical cyclone aila in india.background & objectives : cyclone aila hit indian states on eastern coast on may 25, 2009. an investigation was conducted to examine if aila was responsible for increased reporting of diarrhoea cases from the district of east-medinipur in west bengal. identifying causative organisms for diarrhoea and assessing their antibiotic susceptibility profile were other objectives. methods: rapid situation and response assessment technique was employed to triangulate primary and secondary data collected t ...201121537092
development of a new guinea-pig model of shigellosis.shigellosis is a major form of bacillary dysentery caused by shigella spp. to date, there is no suitable animal model to evaluate the protective efficacy of vaccine candidates against this pathogen. here, we describe a successful experimental shigellosis in the guinea-pig model, which has shown the characteristic features of human shigellosis. this model yielded reproducible results without any preparatory treatment besides cecal ligation. in this study, guinea-pigs were discretely infected with ...201121539623
transient suppression of shigella flexneri type 3 secretion by a protective o-antigen-specific monoclonal iga.abstract mucosal immunity to the enteric pathogen shigella flexneri is mediated by secretory iga (s-iga) antibodies directed against the o-antigen (o-ag) side chain of lipopolysaccharide. while secretory antibodies against the o-ag are known to prevent bacterial invasion of the intestinal epithelium, the mechanisms by which this occurs are not fully understood. in this study, we report that the binding of a murine monoclonal iga (igac5) to the o-ag of s. flexneri serotype 5a suppresses activity ...201121610121
dynamic aspects of antibody:oligosaccharide complexes characterized by molecular dynamics simulations and std-nmr.carbohydrates are likely to maintain significant conformational flexibility in antibody:carbohydrate complexes. as demonstrated herein for the protective monoclonal antibody f22-4 recognizing the shigella flexneri 2a o-antigen and numerous synthetic oligosaccharide fragments thereof, the combination of molecular dynamics simulations and nmr saturation transfer difference experiments, supported by physicochemical analysis, allows to determine the binding epitope and its various contributions to a ...201121610193
identification of small-molecule inhibitors of yersinia pestis type iii secretion system yscn atpase.yersinia pestis is a gram negative zoonotic pathogen responsible for causing bubonic and pneumonic plague in humans. the pathogen uses a type iii secretion system (t3ss) to deliver virulence factors directly from bacterium into host mammalian cells. the system contains a single atpase, yscn, necessary for delivery of virulence factors. in this work, we show that deletion of the catalytic domain of the yscn gene in y. pestis co92 attenuated the strain over three million-fold in the swiss-webster ...201121611119
a novel compound from the marine bacterium bacillus pumilus s6-15 inhibits biofilm formation in gram-positive and gram-negative species.biofilm formation is a critical problem in nosocomial infections and in the aquaculture industries and biofilms show high resistance to antibiotics. the aim of the present study was to reveal a novel anti-biofilm compound from marine bacteria against antibiotic resistant gram-positive and gram-negative biofilms. the bacterial extract (50 μg ml(-1)) of s6-01 (bacillus indicus = mtcc 5559) showed 80-90% biofilm inhibition against escherichia coli, shigella flexneri, proteus mirabilis and s6-15 (ba ...201121614700
complete (1)h and (13)c nmr chemical shift assignments of mono-, di-, and trisaccharides as basis for nmr chemical shift predictions of polysaccharides using the computer program casper.the computer program casper uses (1)h and (13)c nmr chemical shift data of mono- to trisaccharides for the prediction of chemical shifts of oligo- and polysaccharides. in order to improve the quality of these predictions the (1)h and (13)c, as well as (31)p when applicable, nmr chemical shifts of 30 mono-, di-, and trisaccharides were assigned. the reducing sugars gave two distinct sets of nmr resonances due to the α- and β-anomeric forms. in total 35 (1)h and (13)c nmr chemical shift data sets ...201121621752
synthesis, characterization and biological properties of thienyl derived triazole schiff bases and their oxovanadium(iv) complexes.a new series of biologically active thienyl derived triazole schiff bases and their oxovanadium(iv) complexes have been synthesized and characterized on the basis of physical (m.p., magnetic susceptibility and conductivity), spectral (ir, (1)h and (13)c nmr, electronic and mass spectrometry) and microanalytical data. all the schiff base ligands and their oxovanadium(iv) complexes have been subjected to in vitro antibacterial activity against four gram-negative (escherichia coli, shigella flexner ...201121635212
structure-guided investigation of lipopolysaccharide o-antigen chain length regulators reveals regions critical for modal length control.the o-antigen component of the lipopolysaccharide (lps) represents a population of polysaccharide molecules with a non-random (modal) chain length distribution. the number of the repeat o-units in each individual o-antigen polymer depends on the wzz chain-length regulator, an inner membrane protein belonging to the polysaccharide co-polymerase (pcps) family. different wzz proteins confer vastly different ranges of modal lengths (4 to >100 repeat units) despite having remarkably conserved structu ...201121642455
production of bioactive sheep β-defensin-1 in pichia pastoris.previous research has shown that sheep β-defensin-1 (sbd-1), a small cationic peptide with a broad range of antimicrobial activities, could inhibit the growth of both gram-positive and gram-negative bacteria as well as that of fungi. in order to increase the yield of current ovine defensin purification methods, mature sbd-1 (msbd-1) was added with a 6-his tag on the c-terminus (msbd-1-t) and expressed in pichia pastoris in the presented work. the msbd-1 and msbd-1-t were expressed in the pichia ...201121643707
p62 and ndp52 target intracytosolic shigella and listeria to different autophagy pathways.autophagy is an important mechanism of innate immune defense. we have recently shown that autophagy components are recruited with septins, a new and increasingly characterized cytoskeleton component, to intracytosolic shigella that have started to polymerize actin. on the other hand, intracytosolic listeria avoids autophagy recognition by expressing acta, a bacterial effector required for actin polymerization. here we exploit shigella and listeria as intracytosolic tools to characterize differen ...201121646350
gisul2, a genomic island carrying the sul2 sulphonamide resistance gene and the small mobile element cr2 found in the enterobacter cloacae subspecies cloacae type strain atcc 13047 from 1890, shigella flexneri atcc 700930 from 1954 and acinetobacter baumannii atcc 17978 from 1951. 201121653606
modulation of connexin signaling by bacterial pathogens and their toxins.inherent to their pivotal tasks in the maintenance of cellular homeostasis, gap junctions, connexin hemichannels, and pannexin hemichannels are frequently involved in the dysregulation of this critical balance. the present paper specifically focuses on their roles in bacterial infection and disease. in particular, the reported biological outcome of clinically important bacteria including escherichia coli, shigella flexneri, yersinia enterocolitica, helicobacter pylori, bordetella pertussis, aggr ...201121656255
genetic characteristics and changing antimicrobial resistance among shigella spp isolated from hospitalized diarrhoeal patients in kolkata, india.to study the prevalence pattern and trends in the phenotypic and genetic characteristics of shigellae, we tested 212 isolates isolated from diarrhoeal patients admitted at the infectious diseases hospital, kolkata, india from november 2007 to october 2009. prevalence of shigella spp was more in more than 5 years age group (69%) than the children >5 years age group (31%). serotypes 2a, 3a and untypable isolates of the subtype s. flexneri were frequently detected. increase in the isolation of s. s ...201121659504
the future is cold: cryo-preparation methods for transmission electron microscopy of cells.our knowledge of the organization of the cell is linked, to a great extent, to light and electron microscopy. choosing either photons or electrons for imaging has many consequences on the image obtained, as well as on the experiment required in order to generate the image. one apparent effect on the experimental side is in the sample preparation, which can be quite elaborate for electron microscopy. in recent years, rapid freezing, cryo-preparation and cryo-electron microscopy have been more wid ...201121812762
the vibrio cholerae vctpdgc system transports catechol siderophores and a siderophore-free iron ligand.vibrio cholerae, the causative agent of cholera, has an absolute requirement for iron. it transports the catechol siderophores vibriobactin, which it synthesizes and secretes, and enterobactin. these siderophores are transported across the inner membrane by one of two periplasmic binding protein-dependent abc transporters, vctpdgc or viupdgc. we show here that one of these inner membrane transport systems, vctpdgc, also promotes iron acquisition in the absence of siderophores. plasmids carrying ...201121790806
safety, and immunogenicity of an intranasal shigella flexneri 2a invaplex 50 vaccine.background: shigella flexneri 2a invaplex 50 is a nasally delivered subunit vaccine consisting of a macromolecular complex composed of lps, ipab, ipac and ipad. the current study examined vaccine safety and immunogenicity across a dose range and the clinical performance of a new intranasal delivery device. methods: volunteers (n=36) were randomized to receive vaccine via the dolphin™ (valois of america, congers, new york) intranasal spray device at one of three doses (240, 480, and 690µg) on day ...201121787825
serine protease autotransporters from shigella flexneri and pathogenic escherichia coli target a broad range of leukocyte glycoproteins.the serine protease autotransporters of enterobacteriaceae (spates) are secreted by pathogenic gram-negative bacteria through the autotransporter pathway. we previously classified spate proteins into two classes: cytotoxic (class 1) and noncytotoxic (class 2). here, we show that pic, a class 2 spate protein produced by shigella flexneri 2a, uropathogenic and enteroaggregative escherichia coli strains, targets a broad range of human leukocyte adhesion proteins. substrate specificity was restricte ...201121768350
lipopolysaccharide core structures and their correlation with genetic groupings of shigella strains; a novel core variant in shigella boydii type 16.bacteria shigella, the cause of shigellosis, evolved from intestinal bacteria escherichia coli. based on structurally diverse o-specific polysaccharide chains of the lipopolysaccharides (o-antigens), three from four shigella species are subdivided into multiple serotypes. the central oligosaccharide of the lipopolysaccharide called core is usually conserved within genus but five core types called r1-r4 and k-12 have been recognized in e. coli. structural data on the shigella core are limited to ...201121752864
outer membrane protein a (ompa) of shigella flexneri 2a, induces protective immune response in a mouse model.in our earlier studies 34 kda outer membrane protein (omp) of shigella flexneri 2a has been identified as an efficient immunostimulant.201121818362
studies on the activity of cyperus rotundus linn. tubers against infectious diarrhea.to study the antidiarrheal activity of the decoction of cyperus rotundus linn. tubers using representative assays of diarrheal pathogenesis and understand its mechanism of action.antibacterial, antigiardial and antirotaviral activities were studied. effect on adherence of enteropathogenic escherichia coli (epec) and invasion of enteroinvasive e. coli (eiec) and shigella flexneri to hep-2 cells was evaluated as a measure of effect on colonization. effect on enterotoxins such as enterotoxigenic e. ...201121713044
recovery and characterization of environmental variants of shigella flexneri from surface water in bangladesh.little is known about the distribution, survival, and transmission of shigella in environmental surface waters. to gain more insight into the environmental biology of shigella we isolated five bacterial strains serotyped as shigella flexneri 2b from a freshwater lake in bangladesh using a modified nutrient broth supplemented with nucleic acid bases. the biochemical properties of the isolates, including inability to ferment lactose and a negative lysine decarboxylase test, indicated common physio ...201121826486
structural and functional studies on the n-terminal domain of the shigella type iii secretion protein mxig.mxig is a single-pass membrane protein that oligomerizes within the inner membrane ring of the shigella flexneri type iii secretion system (t3ss). the mxig n-terminal domain (mxig-n) is the predominant cytoplasmic structure; however, its role in t3ss assembly and secretion is largely uncharacterized. we have determined the solution structure of mxig-n residues 6-112 (mxig-n(6-112)), representing the first published structure of this t3ss domain. the structure shows strong structural homology to ...201121733840
a multifactor regulatory circuit involving h-ns, virf and an antisense rna modulates transcription of the virulence gene icsa of shigella flexneri.the icsa gene of shigella encodes a structural protein involved in colonization of the intestinal mucosa by bacteria. this gene is expressed upon invasion of the host and is controlled by a complex regulatory circuit involving the nucleoid protein h-ns, the arac-like transcriptional activator virf, and a 450ôçënt antisense rna (rnag) acting as transcriptional attenuator. we investigated on the interplay of these factors at the molecular level. dnase i footprints reveal that both h-ns and virf bi ...201121724612
antibacterial dimeric copper(ii) complexes with chromone-derived compounds.a new series of six chromone-derived compounds and their cu(ii) complexes have been synthesized and characterized by their physical, spectral and analytical data. the ligands and their cu(ii) complexes were screened for their in vitro antibacterial activity against four gram-negative (escherichia coli, pseudomonas aeruginosa, salmonella typhi, shigella flexneri) and two gram-positive (bacillus subtilis, staphylococcus aureus) bacterial strains by agar-well diffusion method. the ligands were foun ...201121699463
espg of enteropathogenic and enterohemorrhagic e. coli binds the golgi matrix protein gm130 and disrupts the golgi structure and function.the enteric pathogens enteropathogenic escherichia coli (epec), enterohaemorrhagic e. coli (ehec) and shigella flexneri all translocate at least one effector protein of the espg protein family into host cells via a type iii secretion system (t3ss). the espg family comprises espg, espg2 and vira. from a y2h screen, we identified the golgi matrix protein gm130 as a potential binding partner of espg. we confirmed espg:gm130 protein interaction by affinity co-purification. in co-immunoprecipitation ...201121740499
atomic structure of bacteriophage sf6 tail needle knob.podoviridae are double-stranded dna bacteriophages that use short, non-contractile tails to adsorb to the host cell surface. within the tail apparatus of p22-like phages, a dedicated fiber known as the "tail needle" likely functions as a cell envelope-penetrating device to promote ejection of viral dna inside the host. in sf6, a p22-like phage that infects shigella flexneri, the tail needle presents a c-terminal globular knob. this knob, absent in phage p22 but shared in other members of the p22 ...201121705802
volatile compounds and antimicrobial and antioxidant activities of the essential oils of the needles of pinus densiflora and pinus thunbergii.to investigate the volatile compounds and the antibacterial and antioxidant effects of the essential oils of pinus densiflora needles (epdn) and pinus thunbergii needles (eptn), the volatile compounds of steam-distilled essential oils were analysed by gas chromatography-mass spectrometry. antibacterial activities were analysed by performing disc-agar diffusion assay and determining the minimum inhibitory concentrations (mics) of the essential oils. antioxidant activities were analysed via radica ...201121213230
shigella enterotoxin-2 is a type iii effector that participates in shigella-induced interleukin 8 secretion by epithelial cells.we have previously described a protein termed shigella enterotoxin 2 (shet-2), which induces rises in short-circuit current in rabbit ileum mounted in the ussing chamber. published reports have postulated that shet-2 may be secreted by the shigella type iii secretion system (t3ss). in this study, we show that shet-2 secretion into the extracellular space requires the t3ss in shigella flexneri 2a strain 2457t and a shet-2-tem fusion was translocated into epithelial cells in a t3ss-dependent manne ...201121219446
two promoters and two translation start sites control the expression of the shigella flexneri outer membrane protease icsp.the shigella flexneri outer membrane protease icsp proteolytically cleaves the actin-based motility protein icsa from the bacterial surface. the icsp gene is monocistronic and lies downstream of an unusually large intergenic region on the shigella virulence plasmid. in silico analysis of this region predicts a second transcription start site 84 bp upstream of the first. primer extension analyses and beta-galactosidase assays demonstrate that both transcription start sites are used. both promoter ...201121225241
analysis of shigella flexneri-mediated infections in model organism caenorhabditis elegans.shigella flexneri is the causative agent of bacillary dysentery and generates a significant global disease burden. the aim of this study was to analyze the pathogenesis and host immune response, at both the physiological and molecular level, using the model organism caenorhabditis elegans, in response to s. flexneri. c. elegans is a nematode that responds to infection with a simple innate immune system, key aspects of which have been shown to be conserved.201121254954
enteric glial cells: new players in mucosal defence against bacteria? 201121282131
synthesis, spectral analysis and in vitro microbiological evaluation of novel ethyl 4-(naphthalen-2-yl)-2-oxo-6-arylcyclohex-3-enecarboxylates and 4,5-dihydro-6-(napthalen-2-yl)-4-aryl-2h-indazol-3-ols.a series of ethyl 4-(naphthalen-2-yl)-2-oxo-6-arylcyclohex-3-enecarboxylates 8-14 and 4,5-dihydro-6-(naphthalen-2-yl)-4-aryl-2h-indazol-3-ols 15-21 were synthesised and characterised by their spectroscopic data. in vitro microbiological evaluations were carried out for all the newly synthesised compounds 8-21 against clinically isolated bacterial and fungal strains. compounds 9, 12 and 20 against staphylococcus aureus, 10, 12, 20 against ß-haemolytic streptococcus, 11, 17 against bacillus subtil ...201121299432
monitoring shigella flexneri vacuolar escape by flow cytometry.invasive bacterial pathogens such as shigella flexneri force their uptake into non-phagocytic host cells. upon internalization, they rupture the endocytic vacuole and escape into the host cell cytoplasm. recent studies applying fluorescence resonance energy transfer (fret) based methods to track host-pathogen interactions have provided insights into the process of bacterial infection at the single cell level. we have previously reported that the vacuolar escape of invasive bacteria into the host ...201121317555
crystal structure of the autochaperone region from the shigella flexneri autotransporter icsa.the icsa (intracellular spread gene a) autotransporter from shigella flexneri is a key virulence factor. we identified a stable fragment comprising residues 591 to 758, which corresponds to the autochaperone region of the icsa passenger domain. we showed that thermal unfolding of the autochaperone region is reversible and determined its crystal structure at 2.0-å resolution.201121335457
changing species distribution and antimicrobial susceptibility pattern of shigella over a 29-year period (1980-2008).we studied changes in species distribution and antimicrobial resistance patterns of shigella during 1980-2008, using the diarrhoeal diseases surveillance system of dhaka hospital of icddr,b. in hospitalized patients shigella prevalence decreased steadily from 8-12% in the 1980s to 3% in 2008. endemic s. flexneri was the most commonly isolated species (54%). epidemic s. dysenteriae type 1 had two peaks in 1984 and 1993, but was not found after 2000, except for one case in 2004. the therapeutic op ...201120478088
pseudoatrophy of the brain with valproic acid monotherapy.a patient is described who, while on valproic acid monotherapy, developed reversible shrinkage of the brain, documented by computerized tomography with associated cognitive deficit. although pseudoatrophy has been reported with steroid therapy, this is the first implication of an anticonvulsant drug in the etiology of that condition.20113117347
treating erythema chronicum migrans of lyme disease.the efficacy of antibiotic treatment of 117 patients with erythema chronicum migrans of lyme disease was evaluated in terms of the necessity for retreatment and the prevention of the late manifestations of lyme disease. fifty-six patients with a minor form of the illness did not require retreatment and did not develop late manifestations following antibiotic treatment. three pregnant patients were included in this group. fourteen of sixty-one patients with a major form of the illness required re ...20113093544
antisense inhibition of gene expression and growth in gram-negative bacteria by cell-penetrating peptide conjugates of peptide nucleic acids targeted to rpod gene.gram-negative bacteria (gnb) cause common and severe hospital- and community-acquired infections with a high incidence of multidrug resistance (mdr) and mortality. the emergence and spread of mdr-gnb strains limit therapeutic options and highlight the need to develop new therapeutic strategies. in this study, the peptide (rxr)(4)xb- and (kff)(3)k-conjugated peptide nucleic acids (ppnas) were developed to target rpod, which encodes an rna polymerase primary σ(70) that is thought to be essential f ...201122000398
Genesis of a novel Shigella flexneri serotype by sequential infection of serotype-converting bacteriophages SfX and SfI.ABSTRACT: BACKGROUND: Shigella flexneri is the major pathogen causing bacillary dysentery. Fifteen serotypes have been recognized up to now. The genesis of new S. flexneri serotypes is commonly mediated by serotype-converting bacteriophages. Untypeable or novel serotypes from natural infections had been reported worldwide but have not been generated in laboratory. RESULTS: A new S. flexneri serotype-serotype 1 d was generated when a S. flexneri serotype Y strain (native LPS) was sequentially in ...201122208551
Mucosal immunization with Shigella flexneri outer membrane vesicles induced protection in mice.Vaccination appears to be the only rational prophylactic approach to control shigellosis. Unfortunately, there is still no safe and efficacious vaccine available. We investigated the protection conferred by a new vaccine containing outer membrane vesicles (OMVs) from Shigella flexneri with an adjuvant based on nanoparticles in an experimental model of shigellosis in mice. OMVs were encapsulated in poly(anhydride) nanoparticles prepared by a solvent displacement method with the copolymer PMV/MA. ...201121911022
a broadly protective shigella vaccine based on type iii secretion apparatus proteins.shigella ssp. are food and water-borne pathogens that cause severe diarrheal and dysenteric disease associated with high morbidity and mortality. individuals most often affected are children under 5 years of age in the developing world. the existence of multiple shigella serotypes and the heterogenic distribution of pathogenic strains as well as emerging antibiotic resistance require the development of a broadly protective vaccine. all shigella ssp. utilize a type iii secretion system (ttss) to ...201122202122
up-regulation of muc2 and il-1β expression in human colonic epithelial cells by shigella and its interaction with mucins.the entire gastrointestinal tract is protected by a mucous layer, which contains complex glycoproteins called mucins. muc2 is one such mucin that protects the colonic mucosa from invading microbes. the initial interaction between microbes and mucins is an important step for microbial pathogenesis. hence, it was of interest to investigate the relationship between host (mucin) and pathogen interaction, including shigella induced expression of muc2 and il-1β during shigellosis.201122073249
topological characterisation and identification of critical domains within glucosyltransferase iv (gtriv) of shigella flexneri.abstract:201122188643
reflectron maldi tof and maldi tof/tof mass spectrometry reveal novel structural details of native lipooligosaccharides.lipooligosaccharides (los) are powerful gram-negative glycolipids that evade the immune system and invade host animal and vegetal cells. the structural elucidation of los is pivotal to understanding the mechanisms of infection at the molecular level. the amphiphilic nature of los has been the main obstacle for structural analysis by matrix-assisted laser desorption/ionization (maldi) mass spectrometry (ms). our approach has resolved this important issue and has permitted us to obtain reflectron ...201122124985
rational design of an artificial genetic switch: co-option of the h-ns-repressed prou operon by the virb virulence master regulator.the h-ns protein represses the transcription of hundreds of genes in gram-negative bacteria. derepression is achieved by a multitude of mechanisms, many of which involve the binding of a protein to dna at the repressed promoter in a manner that compromises the maintenance of the h-ns-dna nucleoprotein repression complex. the principal virulence gene promoters in shigella flexneri, the cause of bacillary dysentery, are repressed by h-ns. virb, a protein that closely resembles members of the parb ...201121873493
Crystal Structure of the VapBC Toxin-Antitoxin Complex from Shigella flexneri Reveals a Hetero-Octameric DNA-Binding Assembly.Toxin-antitoxin (TA) loci are common in archaea and prokaryotes and allow cells to rapidly adapt to changing environmental conditions through release of active regulators of metabolism. Many toxins are endonucleases that target cellular mRNA and tRNAs, while the antitoxins tightly wrap around the toxins to inhibit them under normal circumstances. The antitoxins also bind to operators in the promoter regions of the cognate TA operon and thereby regulate transcription. For enteric vapBC TA loci, t ...201122037005
synthesis and biological evaluation of some thiazolidinones as antimicrobial agents.a novel series of thiazolidinone derivatives namely 4-(4-dimethylamino-6-{4-[5-(4-ethylpiperazin-1-ylmethyl)-4-oxo-2-phenylthiazolidin-3-yl]-phenylamino}-[1,3,5]triazin-2-yloxy)-1-methyl-1h-quinolin-2-one have been synthesized from the key intermediate 4-[4-(4-aminophenylamino)-6-dimethylamino-[1,3,5]triazin-2-yloxy]-1-methyl-1h-quinolin-2-one (7). condensation reaction of compound 7 with different aldehyde derivatives were performed to obtain schiff base derivatives, which after cyclization gav ...201122182927
antimicrobial and toxicological activities of five medicinal plant species from cameroon traditional medicine.infectious diseases caused by multiresistant microbial strains are on the increase. fighting these diseases with natural products may be more efficacious. the aim of this study was to investigate the in vitro antimicrobial activity of methanolic, ethylacetate (etoac) and hexanic fractions of five cameroonian medicinal plants (piptadeniastum africana, cissus aralioides, hileria latifolia, phyllanthus muellerianus and gladiolus gregasius) against 10 pathogenic microorganisms of the urogenital and ...201121867554
the effect of the potential phoq histidine kinase inhibitors on shigella flexneri virulence.phoq/phop is an important two-component system that regulates shigella virulence. we explored whether the phoq/phop system is a promising target for new antibiotics against s. flexneri infection. by using a high-throughput screen and enzymatic activity coupled assay, four compounds were found as potential phoq inhibitors. these compounds not only inhibited the activity of sf-phoqc autophosphorylation but also displayed high binding affinities to the sf-phoqc protein in the surface plasmon resona ...201121853073
neurological manifestations of shigellosis in children in southwestern iran. 201122115119
waterlogsy nmr experiments in conjunction with molecular-dynamics simulations identify immobilized water molecules that bridge peptide mimic mdwnmhaa to anticarbohydrate antibody sya/j6.x-ray crystallographic data of the carbohydrate mimic mdwnmhaa when bound to an anti-shigella flexneri y mab sya/j6 indicate the immobilization of water molecules, that is, the presence of "bound" waters, in the active site. water ligand observed via gradient spectroscopy (waterlogsy) was used in conjunction with saturation transfer difference (std)-nmr spectroscopy to probe the existence of immobilized water molecules in the complex of mdwnmhaa 1 bound to mab sya/j6. molecular dynamics simulati ...201121887835
analysis of synonymous codon usage in shigella flexneri 2a strain 301 and other shigella and escherichia coli strains.in this study, we analysed synonymous codon usage in shigella flexneri 2a strain 301 (sf301) and performed a comparative analysis of synonymous codon usage patterns in sf301 and other strains of shigella and escherichia coli. although there was a significant variety in codon usage bias among different sf301 genes, there was a slight but observable codon usage bias that could primarily be attributable to mutational pressure and translational selection. in addition, the relative abundance of dinuc ...201122112197
the role of oxyr and soxrs in oxidative stress survival in shigella flexneri.shigella flexneri, a facultative intracellular pathogen, is exposed to a variety of environments inside and outside of the human host. some of these environments may contain significant oxidative stress. s. flexneri mutants were generated with deletions in the major oxidative stress regulators oxyr and/or soxrs to test their importance in shigella biology. strains that contained a deletion of oxyr had reduced growth and survival during aerobic growth, but not microaerobic growth. the mutants wer ...201122015257
shigella flexneri infection generates the lipid pi5p to alter endocytosis and prevent termination of egfr signaling.the phosphoinositide metabolic pathway, which regulates cellular processes implicated in survival, motility, and trafficking, is often subverted by bacterial pathogens. shigella flexneri, a bacterium that causes dysentery, injects ipgd, a phosphoinositide phosphatase that generates the lipid phosphatidylinositol 5-phosphate (pi5p), into host cells, thereby activating the phosphoinositide 3-kinase-akt survival pathway. we show that epidermal growth factor receptor (egfr) is required for pi5p-depe ...201121934107
interaction of concanavalin a with bacterial lipopolysaccharides in agarose gel.binding of fluorescein isothiocyanate-labeled concanavalin a to a series of molecular species of lipopolysaccharide (lps), purified from pathogenic bacteria, was studied via agarose gel precipitation experiments and the results were compared with available structural data.the lps species could be divided into cona-reactive and non-reactive ones. reactivity resided in the o-specific chain of lps, and binding to the lipid a or core moieties of lps could not be demonstrated by the present methods. ...201121983321
[Etiological aspects of acute gastroenteritis--a ten-year review (1.01. 2001-31.12.2010)].Acute gastroentritis is one of the most common diseases in humans, and continues to be a significant cause of morbidity worldwide.201122046776
Morning Glory Resin Glycosides as Modulators of Antibiotic Activity in Multidrug-Resistant Gram-Negative Bacteria.Twenty-six microbiologically inactive (MIC >?512?µg/mL) convolvulaceous resin glycosides ( 1- 26) were tested for resistance modulatory activity IN VITRO against ESCHERICHIA COLI Rosetta-gami and two nosocomial pathogens, SALMONELLA TYPHI and SHIGELLA FLEXNERI. These compounds exerted a potentiation effect of the clinically useful antibiotics tetracycline, kanamycin, and chloramphenicol against the tested gram-negative bacteria by increasing antibiotic susceptibility up to 32-fold at concent ...201122002849
Development of a multiplex PCR assay targeting O-antigen modification genes for molecular serotyping of Shigella flexneri.Shigella flexneri is the major Shigella species that causes diarrheal disease in developing countries. It is further subdivided into 15 serotypes based on O-antigen structure. Serotyping of S. flexneri is important for epidemiological purposes. In this study, we developed a multiplex PCR assay targeting the O-antigen synthesis gene wzx and the O-antigen modification genes gtrI, gtrIC, gtrII, oac, gtrIV, gtrV, and gtrX for molecular serotyping of S. flexneri. The multiplex PCR assay contained eig ...201121880974
The iron-responsive Fur/RyhB regulatory cascade modulates the Shigella outer membrane protease IcsP.Actin-based motility is central to the pathogenicity of the intracellular bacterial pathogen Shigella. Two Shigella outer membrane proteins, IcsA and IcsP, are required for efficient actin-based motility in the host cell cytoplasm, and the genes encoding both proteins are carried on the large virulence plasmid. IcsA triggers actin polymerization on the surface of the bacterium, leading to the formation of an actin tail that allows both intra- and intercellular spread. IcsP, an outer membrane pro ...201121859852
a 35 kda antigenic protein from shigella flexneri: in silico structural and functional studies.shigella flexneri serotype 2a is a major public health concern in the developing and under-developed countries which contributes to shigellosis endemic and mortality. thus, there is an urgent need for a rapid diagnostic test for effective therapy and disease management. previous study showed that a ∼35 kda antigenic protein from s. flexneri is a potential biomarker. we therefore modelled the three-dimensional structure of the antigen to probe its functionality which could aid in the development ...201121982766
emergence of ceftriaxone resistant shigella.shigellosis is endemic in many resource-poor countries due to feco-oral transmission, resulting in considerable morbidity and mortality. there is rapid emergence of multi-drug resistant (mdr) shigella spp. resulting in poor reliability of first line antibiotics like quinolones, co-trimoxazole and ampicillin. ceftriaxone has been used as a reserved antibiotic for treatment of mdr shigella spp. the authors report a case of ceftriaxone resistant shigella flexneri successfully managed with meropenem ...201122205379
Investigation of the binding of a carbohydrate-mimetic peptide to its complementary anticarbohydrate antibody by STD-NMR spectroscopy and molecular-dynamics simulations.Saturation transfer difference (STD)-NMR spectroscopy was used to probe experimentally the bioactive solution conformation of the carbohydrate mimic MDWNMHAA 1 of the O-polysaccharide of Shigella flexneri Y when bound to its complementary antibody, mAb SYA/J6. Molecular dynamics simulations using the ZymeCAD™ Molecular Dynamics platform were also undertaken to give a more accurate picture of the conformational flexibility and the possibilities for bound ligand conformations. The ligand topology, ...201121953925
a proteogenomic analysis of shigella flexneri using 2d lc-maldi tof/tof.new strategies for high-throughput sequencing are constantly appearing, leading to a great increase in the number of completely sequenced genomes. unfortunately, computational genome annotation is out of step with this progress. thus, the accurate annotation of these genomes has become a bottleneck of knowledge acquisition.201122032405
contribution of the lipopolysaccharide to resistance of shigella flexneri 2a to extreme acidity.shigella flexneri is endemic in most underdeveloped countries, causing diarrheal disease and dysentery among young children. in order to reach its target site, the colon, shigella must overcome the acid environment of the stomach. shigella is able to persist in this stressful environment and, because of this ability it can initiate infection following the ingestion of very small inocula. thus, acid resistance is considered an important virulence trait of this bacterium. it has been reported that ...201121984920
bacterial aetiology of diarrhoeal diseases and antimicrobial resistance in dhaka, bangladesh, 2005-2008.summaryinfectious diarrhoea caused by bacterial pathogens contributes to the high level of mortality in developing countries like bangladesh. following standard bacteriological procedures, a total of 14 428 bacterial pathogens were isolated from 56 132 stool samples and rectal swabs collected from diarrhoeal patients between 2005 and 2008. the rate of isolation and antimicrobial susceptibility data were retrospectively analysed for these isolates and among them vibrio spp. (42·9%) were the most ...201122040529
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