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self-adjuvanting bacterial vectors expressing pre-erythrocytic antigens induce sterile protection against malaria.genetically inactivated, gram-negative bacteria that express malaria vaccine candidates represent a promising novel self-adjuvanting vaccine approach. antigens expressed on particulate bacterial carriers not only target directly to antigen-presenting cells but also provide a strong danger signal thus circumventing the requirement for potent extraneous adjuvants. e. coli expressing malarial antigens resulted in the induction of either th1 or th2 biased responses that were dependent on both antige ...201323847617
protein expression, crystallization and preliminary x-ray crystallographic analysis of the isolated shigella flexneri vapc toxin.upon release from the stable complex formed with its antitoxin vapb, the toxin vapc (mvpt) of the gram-negative pathogen shigella flexneri is capable of globally down-regulating translation by specifically cleaving initiator trna(fmet) in the anticodon region. recombinant shigella flexneri vapc(d7a) harbouring an active-site mutation was overexpressed in escherichia coli, purified to homogeneity and crystallized by the vapour-diffusion technique. a preliminary x-ray crystallographic analysis sho ...201323832203
human single-chain urokinase is activated by the omptins pgte of salmonella enterica and pla of yersinia pestis despite mutations of active site residues.fibrinolysis is important in cell migration and tightly regulated by specific inhibitors and activators; of the latter, urokinase (upa) associates with enhancement of cell migration. active upa is formed through cleavage of the single-chain upa (scupa). the salmonella enterica strain 14028r cleaved human scupa at the peptide bond lys158-ile159, the site cleaved also by the physiological activator human plasmin. the cleavage led to activation of scupa, while no cleavage or activation were detecte ...201323763588
providencia alcalifaciens causes barrier dysfunction and apoptosis in tissue cell culture: potent role of lipopolysaccharides on diarrheagenicity.providencia alcalifaciens is a member of the enterobacteriaceae family that occasionally causes diarrheagenic illness in humans via the intake of contaminated foods. despite the epidemiological importance of p. alcalifaciens, little is known about its pathobiology. here we report that p. alcalifaciens causes barrier dysfunction in caco-2 cell monolayers and induces apoptosis in calf pulmonary artery endothelial cells. p. alcalifaciens infection caused a 30% reduction in transepithelial resistanc ...201323710559
the shigella ospc3 effector inhibits caspase-4, antagonizes inflammatory cell death, and promotes epithelial infection.caspase-mediated inflammatory cell death acts as an intrinsic defense mechanism against infection. bacterial pathogens deploy countermeasures against inflammatory cell death, but the mechanisms by which they do this remain largely unclear. in a screen for shigella flexneri effectors that regulate cell death during infection, we discovered that shigella infection induced acute inflammatory, caspase-4-dependent epithelial cell death, which is counteracted by the bacterial ospc3 effector. ospc3 int ...201323684308
shigella antigen-specific b memory cells are associated with decreased disease severity in subjects challenged with wild-type shigella flexneri 2a.the role of shigella-specific b memory (bm) in protection has not been evaluated in human challenge studies. we utilized cryopreserved pre- and post-challenge peripheral blood mononuclear cells and sera from wild-type shigella flexneri 2a (wt-2457t) challenges. challenged volunteers were either naïve or subjects who had previously ingested wt-2457t or been immunized with hybrid escherichia coli-shigella live oral candidate vaccine (ecsf2a-2). bm and antibody titers were measured against lipopoly ...201323649043
recombinant heat shock protein 60 (hsp60/groel) of salmonella enterica serovar typhi elicits cross-protection against multiple bacterial pathogens in mice.heat shock proteins (hsps) or stress proteins are recognized as protective antigens against a wide range of bacterial diseases. conservation of hsps across different life forms also appears to contribute to the antigenicity of these proteins. due to their high sequence homology, there exists an immunological cross-recognition between different bacterial species. in the present study, we evaluated the efficacy of recombinant groel of salmonella enterica serovar typhi as a vaccine candidate agains ...201323474314
tmrna is essential in shigella flexneri.nonstop mrnas pose a challenge for bacteria, because translation cannot terminate efficiently without a stop codon. the trans-translation pathway resolves nonstop translation complexes by removing the nonstop mrna, the incomplete protein, and the stalled ribosome. p1 co-transduction experiments demonstrated that tmrna, a key component of the trans-translation pathway, is essential for viability in shigella flexneri. tmrna was previously shown to be dispensable in the closely related species esch ...201323451240
isolation and genomic characterization of sfi, a serotype-converting bacteriophage of shigella flexneri.all shigella flexneri serotypes except serotype 6 share a common o-antigen tetrasaccharide backbone and nearly all variations between serotypes are due to glucosyl and/or o-acetyl modifications of the common o unit mediated by glycosyltransferases encoded by serotype-converting bacteriophages. several s. flexneri serotype-converting phages including sfv, sfx, sf6 and sfii have been isolated and characterized. however, s. flexneri serotype-converting phage sfi which encodes a type i modification ...201323414301
analysis of soluble protein complexes in shigella flexneri reveals the influence of temperature on the amount of lipopolysaccharide.shigella flexneri, which is closely related to escherichia coli, is the most common cause of the endemic form of shigellosis. in this study, 53 homomultimeric protein complexes and nine heteromultimeric protein complexes from s. flexneri 2a strain 2457t were separated and identified. among these, three potential homomultimeric protein complexes had not been previously described. one complex, thought to be composed of 12 phon1 subunits, is a periplasmic protein with an unknown physiological role ...201323378524
antidiarrhoeal and antimicrobial activity of calpurnia aurea leaf extract.in ethiopia, calpurnia aurea is used for the treatment of syphilis, malaria, rabies, diabetes, hypertension, diarrhoea, leishmaniasis, trachoma, elephantiasis, fungal diseases and different swellings. however, despite its traditional usage as an antidiarrhoeal and antimicrobial agent, there is limited or no information regarding its effectiveness and mode of action in diarrhoea which may be caused by shigella flexneri, staphylococcus aureus, escherichia coli and salmonella typhi. hence, we evalu ...201323351272
one-step sensitive detection of salmonella typhimurium by coupling magnetic capture and fluorescence identification with functional nanospheres.sensitive, rapid, and reliable detection of bacteria has always been pursued due to the great threat of the bacteria to human health. in this study, a convenient one-step strategy for detecting salmonella typhimurium was developed. immunomagnetic nanospheres (imns) and immunofluorescent nanospheres (ifns) were used to specifically capture and recognize s. typhimurium simultaneously. after magnetic separation, the sandwich immune complexes (imns-bacteria-ifns) were detected under a fluorescence m ...201323256523
comparison of ims platforms for detecting and recovering escherichia coli o157 and shigella flexneri in foods.two automated platforms using immunomagnetic separation technology were compared for detecting and recovering escherichia coli o157 in ground beef and sprouts and shigella flexneri in green onions. the foods were inoculated with <20 cfu/25 g and tested at 5 and 24 h postincubation. immunomagnetic beads were mixed with food enrichments, processed through the pathatrix auto or kingfisher flex, and tested by real-time pcr (qpcr) and recovery on selective agars. at 5 h, the pathatrix auto detected e ...201323190790
production of microbial medium from defatted brebra (milletia ferruginea) seed flour to substitute commercial peptone agar.to investigate and optimize microbial media that substitute peptone agar using brebra seed defatted flour.201324075344
safety assessment and probiotic evaluation of enterococcus faecium yf5 isolated from sourdough.enterococcus faecium yf5, a strain previously isolated from sourdough, was assessed for safety and probiotic potential. its virulence and antibiotic resistant phenotypes (cytolysin and gelatinase production, antibiotic susceptibility) and genes (cyla, gele, ace, agg, esp, and vana) were surveyed. results indicated that the tested virulence determinants were nontoxic. in addition, e. faecium yf5 was sensitive to 3 antibiotics such as amoxicillin, vancomycin, and chloramphenicol. furthermore, resu ...201323488799
connexin 26 facilitates gastrointestinal bacterial infection in vitro.escherichia coli, including enteropathogenic e. coli (epec), represents the most common cause of diarrhoea worldwide and is therefore a serious public health burden. treatment for gastrointestinal pathogens is hindered by the emergence of multiple antibiotic resistance, leading to the requirement for the development of new therapies. a variety of mechanisms act in combination to mediate gastrointestinal-bacterial-associated diarrhoea development. for example, epec infection of enterocytes induce ...201323138568
evaluation of probiotic properties of lactobacillus plantarum strains isolated from chinese sauerkraut.lactobacillus plantarum strains isolated and identified from naturally-fermented chinese sauerkraut were examined in vitro for potential probiotic properties and in vivo for cholesterol-lowering effect in mice. among 7 isolated l. plantarum strains, strains s2-5 and s4-1 were found to possess desirable probiotic properties including ability to survive at ph 2.0 for 60 min, tolerate pancreatin and bile salts, adhere to caco-2 cells, produce high β-galactosidase activity and antimicrobial activity ...201323117677
synthesis of monodispersed silver nanoparticles using hibiscus cannabinus leaf extract and its antimicrobial activity.synthesis of silver nanoparticles using leaf extract of hibiscus cannabinus has been investigated. the influences of different concentration of h. cannabinus leaf extract, different metal ion concentration and different reaction time on the above cases on the synthesis of nanoparticles were evaluated. the synthesized nanoparticles were characterized using uv-vis spectroscopy, fourier transform infrared spectroscopy (ftir), x-ray diffraction (xrd) and transmission electron microscopy (tem). the p ...201323103459
quantification of viable but nonculturable bacterial pathogens in anaerobic digested sludge.enteric bacterial pathogens in sewage sludge easily become viable but nonculturable (vbnc) during anaerobic digestion, which escape detection by standard culture methods and pose a potential health risk. in this study, a method that is combining the standard culture method with the reverse transcription quantitative pcr (rt-qpcr) assay was developed for the quantification of bacterial pathogens in the vbnc state. the cycle threshold (ct) values from rt-qpcr assays were linear to the bacterial nu ...201322996281
cloning and purification of ipac antigen from shigella flexneri: proposal of a new methodology.shigella flexneri is a gram-negative bacillus that is responsible for a severe form of dysentery called shigellosis, which mainly affects children and the elderly in both underdeveloped and developed countries. pathogenic s. flexneri strains possess a large virulence plasmid that codes for effector proteins that are required for the entry and spread of the bacteria into colonocytes. among these proteins is the translocator ipac, which plays an important role in the invasion process; ipac is impl ...201322894716
the antimicrobial effect of lactobacillus casei culture supernatant against multiple drug resistant clinical isolates of shigella sonnei and shigella flexneri in vitro.shigellosis remains an important public health problem in developing countries with s. sonnei and s. flexneri in us, europe and in asian countries being of importance.201323682323
technological and probiotic potential of bgra43 a natural isolate of lactobacillus helveticus.lactobacillus helveticus bgra43 is a human intestinal isolate showing antimicrobial activity, amongst others, against yersinia enterocolitica, shigella sonnei, shigella flexneri, and streptococcus pneumoniae. bgra43 produces prth proteinase with proteolytic activity on both casein and β-lactoglobulin (blg). bgra43 is able to reduce the allergenicity of blg. bioactive peptides released in bgra43 fermented milk are potent modulators of innate immunity by modulating the production of proinflammator ...201323346083
molecular mechanisms of cell-cell spread of intracellular bacterial pathogens.several bacterial pathogens, including listeria monocytogenes, shigella flexneri and rickettsia spp., have evolved mechanisms to actively spread within human tissues. spreading is initiated by the pathogen-induced recruitment of host filamentous (f)-actin. f-actin forms a tail behind the microbe, propelling it through the cytoplasm. the motile pathogen then encounters the host plasma membrane, forming a bacterium-containing protrusion that is engulfed by an adjacent cell. over the past two decad ...201323864553
mait cells detect and efficiently lyse bacterially-infected epithelial cells.mucosal associated invariant t cells (mait) are innate t lymphocytes that detect a large variety of bacteria and yeasts. this recognition depends on the detection of microbial compounds presented by the evolutionarily conserved major-histocompatibility-complex (mhc) class i molecule, mr1. here we show that mait cells display cytotoxic activity towards mr1 overexpressing non-hematopoietic cells cocultured with bacteria. the nk receptor, cd161, highly expressed by mait cells, modulated the cytokin ...201324130485
proteolytic elimination of n-myristoyl modifications by the shigella virulence factor ipaj.protein n-myristoylation is a 14-carbon fatty-acid modification that is conserved across eukaryotic species and occurs on nearly 1% of the cellular proteome. the ability of the myristoyl group to facilitate dynamic protein-protein and protein-membrane interactions (known as the myristoyl switch) makes it an essential feature of many signal transduction systems. thus pathogenic strategies that facilitate protein demyristoylation would markedly alter the signalling landscape of infected host cells ...201323535599
shigella flexneri t3ss effector ipah4.5 modulates the host inflammatory response via interaction with nf-κb p65 protein.shigella species possess a type iii secretion system (t3ss), which is required for human infection and that delivers effector proteins into target host cells. here, we show that the effector, ipah4.5 dampens the pro-inflammatory cytokine response. in both the sereny test and a murine lung infection model, the shigella δipah4.5 mutant strain caused more severe inflammatory responses and significantly induced higher pro-inflammatory cytokine levels (mip-2 and tnf-α) in the lung homogenates of wild ...201323083102
protective immunity by oral immunization with heat-killed shigella strains in a guinea pig colitis model.the protective efficacy of and immune response to heat-killed cells of monovalent and hexavalent mixtures of six serogroups/serotypes of shigella strains (shigella dysenteriae 1, shigella flexneri 2a, s. flexneri 3a, s. flexneri 6, shigella boydii 4, and shigella sonnei) were examined in a guinea pig colitis model. a monovalent or hexavalent mixture containing 1 × 10(7) of each serogroup/serotype of heat-killed shigella cells was administered orally on days 0, 7, 14 and 21. on day 28, the immuni ...201324033533
characterization and complete genome sequence of the shigella bacteriophage psf-1.shigellosis is a global health problem, and shigella flexneri is the major cause of this disease. in this study, we isolated a virulent siphoviridae bacteriophage (phage), psf-1, that infects s. flexneri. this phage was isolated from the han river in korea and was found to infect s. flexneri, shigella boydii, and shigella sonnei. one-step growth analysis revealed that this phage has a short latent period (10 min) and a large burst size (86.86 pfu/cell), indicating that psf-1 has good host infect ...201324012542
multi-serotype outer membrane vesicles of shigellae confer passive protection to the neonatal mice against shigellosis.recently, we have demonstrated, immunization of adult female mice with outer membrane vesicles (omvs) of shigella boydii type 4 protected their offspring passively from shigellosis. in our present study, we have advanced our research by formulating multi-serotype outer membrane vesicles (momvs), mixing the omvs of shigella dysenteriae 1 δstx, shigella flexneri 2a, 3a and 6, s. boydii type 4 and shigella sonnei to achieve a broad spectrum protection against shigellosis. adult mice were immunized ...201323684822
phage inactivation of foodborne shigella on ready-to-eat spiced chicken.shigellosis, also called bacillary dysentery, is an infectious disease caused by shigella species, including shigella flexneri, shigella dysenteriae, shigella sonnei, and shigella boydii. infection with s. flexneri can result in epidemics, and shigella-contaminated food is often the source of infection, such as ready-to-eat spiced chicken and duck. therefore, we investigated the ability of shigella phages to inhibit pathogenic shigella spp. in ready-to-eat spiced chicken. food samples were inocu ...201323243250
a role for the ankyrin repeat containing protein ankrd17 in nod1- and nod2-mediated inflammatory responses.innate immune responses induced by the pattern-recognition receptors nod1 and nod2 play pivotal roles to combat infection and to instruct adaptive immunity. here we identify ankrd17 as a novel binding partner of nod2 and show that its n-terminal domain mediates nod2 binding. knock-down and overexpression analysis revealed that ankrd17 is functionally involved in nod2- and nod1-mediated responses in human myeloid and epithelial cells. in hela cells ankrd17 contributed to pro-inflammatory response ...201323711367
molecular cloning and biologically active production of ipad n-terminal region.shigella is known as pathogenic intestinal bacteria in high dispersion and pathogenic bacteria due to invasive plasmid antigen (ipa). so far, a number of ipa proteins have been studied to introduce a new candidate vaccine. here, for the first time, we examined whether the n-terminal region of ipad(72-162) could be a proper candidate for shigella vaccine. initially, the dna sequence coding n-terminal region was isolated by pcr from shigella dysenteriae type i and cloned into pet-28a expression ve ...201323731655
multiplexed immunoassay to assess shigella-specific antibody responses.infection with shigella spp. results in bacillary dysentery and a systemic and mucosal antibody response. the immune response is directed at multiple antigens, including lps and the invasin plasmid antigen (ipa) proteins, and is capable of conferring short-term, serotype-specific protection. both live-attenuated and several subunit vaccine approaches have focused on inducing a pronounced mucosal immune response directed to the same antigens recognized after natural infection. traditionally, shig ...201323583496
impact of dynasore an inhibitor of dynamin ii on shigella flexneri infection.shigella flexneri remains a significant human pathogen due to high morbidity among children < 5 years in developing countries. one of the key features of shigella infection is the ability of the bacterium to initiate actin tail polymerisation to disseminate into neighbouring cells. dynamin ii is associated with the old pole of the bacteria that is associated with f-actin tail formation. dynamin ii inhibition with dynasore as well as sirna knockdown significantly reduced shigella cell to cell spr ...201324367704
a shigella effector dampens inflammation by regulating epithelial release of danger signal atp through production of the lipid mediator ptdins5p.upon infection with shigella flexneri, epithelial cells release atp through connexin hemichannels. however, the pathophysiological consequence and the regulation of this process are unclear. here we showed that in intestinal epithelial cell atp release was an early alert response to infection with enteric pathogens that eventually promoted inflammation of the gut. shigella evolved to escape this inflammatory reaction by its type iii secretion effector ipgd, which blocked hemichannels via the pro ...201324332032
temperature-regulated expression of outer membrane proteins in shigella flexneri.bacteria exist widely in a diversity of natural environments. in order to survive adverse conditions such as nutrient depletion, biochemical and biological disturbances, and high temperature, bacteria have developed a wide variety of coping mechanisms. temperature is one of the most important factors that can enhance the expression of microbial proteins. this study was conducted to investigate how outer membrane proteins (omps) of the bacterium shigella flexneri respond to stress, especially dur ...201324330657
characterization of extended-spectrum beta-lactamase-producing clinical isolates of shigella flexneri. 201324288956
[o-antigen modification and serotype conversion of shigella flexneri]. 201324257184
n-terminus of ipab provides a potential anchor to the shigella type iii secretion system tip complex protein ipad.the type iii secretion system (t3ss) is an essential virulence factor for shigella flexneri , providing a conduit through which host-altering effectors are injected directly into a host cell to promote uptake. the type iii secretion apparatus (t3sa) is composed of a basal body, external needle, and regulatory tip complex. the nascent needle is a polymer of mxih capped by a pentamer of invasion plasmid antigen d (ipad). exposure to bile salts (e.g., deoxycholate) causes a conformational change in ...201324236510
intracellular shigella remodels its lps to dampen the innate immune recognition and evade inflammasome activation.lps is a potent bacterial effector triggering the activation of the innate immune system following binding with the complex cd14, myeloid differentiation protein 2, and toll-like receptor 4. the lps of the enteropathogen shigella flexneri is a hexa-acylated isoform possessing an optimal inflammatory activity. symptoms of shigellosis are produced by severe inflammation caused by the invasion process of shigella in colonic and rectal mucosa. here we addressed the question of the role played by the ...201324167293
epidemiological characteristics of imported shigellosis in korea, 2010-2011.shigellosis is a global disease as food poisoning by infection of shigella spp (s. dysenteriae, s. flexneri, s. boydii and s. sonnei). in korea, approximately 500 cases of shigellosis have reported every year since 2004, and imported shigellosis is increasing gradually from 2006 in particular. according to increase of numbers of overseas travelers, the numbers of patients diseased with imported shigellosis is also increasing. we need continuous surveillance studies network (ssn) for control of i ...201324159548
analysis of the proteome of intracellular shigella flexneri reveals pathways important for intracellular growth.global proteomic analysis was performed with shigella flexneri strain 2457t in association with three distinct growth environments: s. flexneri growing in broth (in vitro), s. flexneri growing within epithelial cell cytoplasm (intracellular), and s. flexneri that were cultured with, but did not invade, henle cells (extracellular). compared to in vitro and extracellular bacteria, intracellular bacteria had increased levels of proteins required for invasion and cell-to-cell spread, including ipa, ...201324101689
[ctx-m-type extended-spectrum β-lactamase in shigella flexneri isolates from pediatric patients with acute diarrhea]. 201324100837
isolation, characterization and comparative genomics of bacteriophage sfiv: a novel serotype converting phage from shigella flexneri.shigella flexneri is the major cause of shigellosis in the developing countries. the o-antigen component of the lipopolysaccharide is one of the key virulence determinants required for the pathogenesis of s. flexneri. the glucosyltransferase and/or acetyltransferase genes responsible for the modification of the o-antigen are encoded by temperate serotype converting bacteriophage present in the s. flexneri genome. several serotype converting phages have previously been isolated and characterized, ...201324090466
characterization of a novel fusion protein from ipab and ipad of shigella spp. and its potential as a pan-shigella vaccine.shigellosis is an important disease in the developing world, where about 90 million people become infected with shigella spp. each year. we previously demonstrated that the type three secretion apparatus (t3sa) proteins ipab and ipad are protective antigens in the mouse lethal pulmonary model. in order to simplify vaccine formulation and process development, we have evaluated a vaccine design that incorporates both of these previously tested shigella antigens into a single polypeptide chain. to ...201324060976
the zebrafish as a new model for the in vivo study of shigella flexneri interaction with phagocytes and bacterial autophagy.autophagy, an ancient and highly conserved intracellular degradation process, is viewed as a critical component of innate immunity because of its ability to deliver cytosolic bacteria to the lysosome. however, the role of bacterial autophagy in vivo remains poorly understood. the zebrafish (danio rerio) has emerged as a vertebrate model for the study of infections because it is optically accessible at the larval stages when the innate immune system is already functional. here, we have characteri ...201324039575
spontaneous mutation frequency and molecular mechanisms of shigella flexneri fluoroquinolone resistance under antibiotic selective stress.the incidence of fluoroquinolone-resistant shigella strains has risen rapidly, presumably in response to ciprofloxacin antibiotic stress. understanding the molecular mechanisms underlying this resistance phenotype is critical to developing novel and effective therapeutic strategies. in this study, the frequency of ciprofloxacin-induced mutation was measured in antibiotic resistance genes (gyra, gyrb, parc, pare, maror, and mara) of shigella flexneri. the s. flexneri 2a strain 301 was cultured on ...201323070800
towards a non-living vaccine against shigella flexneri: from the inactivation procedure to protection studies.shigellosis is one of the leading causes of diarrhea worldwide with more than 165 million cases annually. hence, a vaccine against this disease is a priority, but no licensed vaccine is still available. considering target population as well as intrinsic risks of live attenuated vaccines, non-living strategies appear as the most promising candidates. remarkably, the preservation of antigenic properties is a major concern since inactivation methods of bacteria affect these qualities. we previously ...201323046911
complete genome sequence of sfii, a serotype-converting bacteriophage of the highly prevalent shigella flexneri serotype 2a.sfii is a serotype-converting temperate bacteriophage of the highly prevalent shigella flexneri serotype 2a. we isolated the sfii phage from a wild-type strain of s. flexneri serotype 2a. here, we present the complete genome sequence of this phage.201324029753
identification of shigella flexneri icsa residues affecting interaction with n-wasp, and evidence for icsa-icsa co-operative interaction.the shigella flexneri icsa (virg) protein is a polarly distributed outer membrane protein that is a fundamental virulence factor which interacts with neural wiskott-aldrich syndrome protein (n-wasp). the activated n-wasp then activates the arp2/3 complex which initiates de novo actin nucleation and polymerisation to form f-actin comet tails and allows bacterial cell-to-cell spreading. in a previous study, icsa was found to have three n-wasp interacting regions (irs): ir i (aa 185-312), ir ii (aa ...201323405119
residues located inside the escherichia coli fepe protein oligomer are essential for lipopolysaccharide o-antigen modal chain length regulation.the escherichia coli o157 : h7 fepe protein regulates lipopolysaccharide (lps) o-antigen (oag) chain length to confer a very long modal chain length of >80 oag repeat units (rus). the mechanism by which fepe regulates oag modal chain length and the regions within it that are important for its function remain unclear. studies on the structure of fepe show that the protein oligomerizes. however, the exact size of the oligomer is in dispute, further hampering our understanding of its mechanism. gui ...201323393150
o-antigen structure of shigella flexneri serotype yv and effect of the lpt-o gene variation on phosphoethanolamine modification of s. flexneri o-antigens.shigella flexneri is the major human pathogen causing shigellosis. o-antigens of all s. flexneri serotypes (except for serotype 6) share the →2)-α-l-rhap(iii)-(1 → 2)-α-l-rhap(ii)-(1 → 3)-α-l-rhap(i)-(1 → 3)-β-d-glcpnac-(1→ basic o-unit, whereas differences between the serotypes are conferred by phage-encoded glucosylation and/or o-acetylation at various positions. recently, in serotype x and 4a variants called xv and 4av, respectively, o-antigen modification with phosphoethanolamine (petn) has ...201323283000
human plasma-derived polymeric iga and igm antibodies associate with secretory component to yield biologically active secretory-like antibodies.immunotherapy with monoclonal and polyclonal immunoglobulin is successfully applied to improve many clinical conditions, including infection, autoimmune diseases, or immunodeficiency. most immunoglobulin products, recombinant or plasma-derived, are based on igg antibodies, whereas to date, the use of iga for therapeutic application has remained anecdotal. in particular, purification or production of large quantities of secretory iga (siga) for potential mucosal application has not been achieved. ...201323250751
bruton's tyrosine kinase regulates shigella flexneri dissemination in ht-29 intestinal cells.shigella flexneri is a gram-negative intracellular pathogen that infects the intestinal epithelium and utilizes actin-based motility to spread from cell to cell. s. flexneri actin-based motility has been characterized in various cell lines, but studies in intestinal cells are limited. here we characterized s. flexneri actin-based motility in ht-29 intestinal cells. in agreement with studies conducted in various cell lines, we showed that s. flexneri relies on neural wiskott-aldrich syndrome prot ...201323230296
myosin-x facilitates shigella-induced membrane protrusions and cell-to-cell spread.the intracellular pathogen shigella flexneri forms membrane protrusions to spread from cell to cell. as protrusions form, myosin-x (myo10) localizes to shigella. electron micrographs of immunogold-labelled shigella-infected hela cells reveal that myo10 concentrates at the bases and along the sides of bacteria within membrane protrusions. time-lapse video microscopy shows that a full-length myo10 gfp-construct cycles along the sides of shigella within the membrane protrusions as these structures ...201323083060
structural insights into virb-dna complexes reveal mechanism of transcriptional activation of virulence genes.virb activates transcription of virulence genes in shigella flexneri by alleviating heat-stable nucleoid-structuring protein-mediated promoter repression. virb is unrelated to the conventional transcriptional regulators, but homologous to the plasmid partitioning proteins. we determined the crystal structures of virb hth domain bound by the cis-acting site containing the inverted repeat, revealing that the virb-dna complex is related to parb-pars-like complexes, presenting an example that a parb ...201323985969
lps unmasking of shigella flexneri reveals preferential localisation of tagged outer membrane protease icsp to septa and new poles.the shigella flexneri outer membrane (om) protease icsp (sopa) is a member of the enterobacterial omptin family of proteases which cleaves the polarly localised om protein icsa that is essential for shigella virulence. unlike icsa however, the specific localisation of icsp on the cell surface is unknown. to determine the distribution of icsp, a haemagglutinin (ha) epitope was inserted into the non-essential icsp om loop 5 using splicing by overlap extension (soe) pcr, and icsp(ha) was characteri ...201323936222
identification and characterization of a novel shigella flexneri serotype yv in china.shigella flexneri is the major cause of bacterial shigellosis in developing countries. s. flexneri is divided into at least 19 serotypes, the majority of which are modifications of the same basic o-antigen by glucosylation and/or o-acetylation of its sugar residues by phage encoded serotype-converting genes. recently, a plasmid encoded phosphoethanolamine (petn) modification of the o-antigen has been reported, which is responsible for the presence of the masf iv-1 determinant and results in conv ...201323936172
in situ structural analysis of the yersinia enterocolitica injectisome.injectisomes are multi-protein transmembrane machines allowing pathogenic bacteria to inject effector proteins into eukaryotic host cells, a process called type iii secretion. here we present the first three-dimensional structure of yersinia enterocolitica and shigella flexneri injectisomes in situ and the first structural analysis of the yersinia injectisome. unexpectedly, basal bodies of injectisomes inside the bacterial cells showed length variations of 20%. the in situ structures of the y. e ...201323908767
infrequent cross-transmission of shigella flexneri 2a strains among villages of a mountainous township in taiwan with endemic shigellosis.shigellosis is rare in taiwan, with an average annual incidence rate of 1.68 cases per 100,000 persons in 2000-2007. however, the incidence rate for a mountainous township in eastern taiwan, zhuoxi, is 60.2 times the average rate for the entire country. traveling between zhuoxi's 6 villages (v1-v6) is inconvenient. disease transmission among the villages/tribes with endemic shigellosis was investigated in this study.201323899288
virulent shigella flexneri affects secretion, expression, and glycosylation of gel-forming mucins in mucus-producing cells.mucin glycoproteins are secreted in large amounts by the intestinal epithelium and constitute an efficient component of innate immune defenses to promote homeostasis and protect against enteric pathogens. in this study, our objective was to investigate how the bacterial enteropathogen shigella flexneri, which causes bacillary dysentery, copes with the mucin defense barrier. we report that upon in vitro infection of mucin-producing polarized human intestinal epithelial cells, virulent s. flexneri ...201323876800
medicinal potential of morella serata (lam.) killick (myricaceae) root extracts: biological and pharmacological activities.morella serata is a south african medicinal plant used in the treatment of microbial infections and to enhance male sexual performance. there is dearth of information in scientific literature on its efficacy and safety.201323829770
systems-level overview of host protein phosphorylation during shigella flexneri infection revealed by phosphoproteomics.the enteroinvasive bacterium shigella flexneri invades the intestinal epithelium of humans. during infection, several injected effector proteins promote bacterial internalization, and interfere with multiple host cell responses. to obtain a systems-level overview of host signaling during infection, we analyzed the global dynamics of protein phosphorylation by liquid chromatography-tandem ms and identified several hundred of proteins undergoing a phosphorylation change during the first hours of i ...201323828894
antimicrobial resistance and genetic characteristics of integron-carrier shigellae isolated in hungary (1998-2008).antimicrobial susceptibility, integron carriage, genetic relationship and presence of some important virulence genes of the integron-carrier strains of shigella sonnei (n = 230) and shigella flexneri (n = 22) isolated from stool samples of patients in hungary between 1998 and 2008 were investigated. sixty-seven per cent (168/252) of the strains were resistant to sulfamethoxazole/trimethoprim (sxt) followed by streptomycin (s, 47%), ampicillin (a, 32%) and tetracycline (tc, 28%). thirty-six per c ...201323800597
outer membrane protein a (ompa) from shigella flexneri 2a: a promising subunit vaccine candidate.shigellosis is the leading cause of childhood mortality and morbidity. despite many years of extensive research a practical vaccine is not yet available against the disease. recent studies illustrate that bacterial outer membrane proteins are budding target as vaccine antigen. outer membrane proteins a (ompa) are among the most immunodominant antigens in the outer membrane of gram negative bacteria and possess many characteristics desired of a vaccine candidate. we observe that ompa of shigella ...201323764536
multidrug-resistant atypical variants of shigella flexneri in china.we identified 3 atypical shigella flexneri varieties in china, including 92 strains with multidrug resistance, distinct pulse types, and a novel sequence type. atypical varieties were prevalent mainly in developed regions, and 1 variant has become the dominant shigella spp. serotype in china. improved surveillance will help guide the prevention and control of shigellosis.201323763754
agglutinating secretory iga preserves intestinal epithelial cell integrity during apical infection by shigella flexneri.shigella flexneri, by invading intestinal epithelial cells (iecs) and inducing inflammatory responses of the colonic mucosa, causes bacillary dysentery. although m cells overlying peyer's patches are commonly considered the primary site of entry of s. flexneri, indirect evidence suggests that bacteria can also use iecs as a portal of entry to the lamina propria. passive delivery of secretory iga (siga), the major immunoglobulin secreted at mucosal surfaces, has been shown to protect rabbits from ...201323753631
nanoparticle-based vaccine for mucosal protection against shigella flexneri in mice.shigellosis is one of the leading causes of diarrhea worldwide with more than 130 million cases annually. hence, the research of an effective vaccine is still a priority. unfortunately, a safe and efficacious vaccine is not available yet. we have previously demonstrated the capacity of outer membrane vesicles (omvs) to protect mice against an experimental infection with shigella flexneri. now, we present results on the capacity of this antigenic complex to confer a longer-term protection by oral ...201323727423
[virulence genes and pathogenicity of shigella flexneri xv isolated in beijing].to understand the biochemical characteristics, virulence genes and pathogenicity of shigella flexneri xv isolated in beijing.201323648252
genetic characterization of antimicrobial resistance of shigella flexneri 1c isolates from patients in egypt and pakistan.shigella flexneri serotype 1c emerged as a critical isolate from children in egypt and pakistan. the pattern of antimicrobial susceptibility (ams) and resistance genes of this serotype have yet to be characterized.201323638855
structure of the o-antigen of a novel shigella flexneri serotype, 1d (i: 7,8).recently, strains of a novel shigella flexneri serotype called 1d have been isolated from diarrheal patients in china. they are distinguished by the presence of a hitherto unknown combination of type o-factor i and group o-factor 7,8, both associated with lateral α-d-glucosyl groups on the basal linear o-polysaccharide. a serologically identical strain, 036_1d, has been constructed in the laboratory by sequential infection of serotype y by serotype-converting bacteriophages sfx and sfi. in this ...201323603189
the common structural architecture of shigella flexneri and salmonella typhimurium type three secretion needles.the type three secretion system (t3ss), or injectisome, is a macromolecular infection machinery present in many pathogenic gram-negative bacteria. it consists of a basal body, anchored in both bacterial membranes, and a hollow needle through which effector proteins are delivered into the target host cell. two different architectures of the t3ss needle have been previously proposed. first, an atomic model of the salmonella typhimurium needle was generated from solid-state nmr data. the needle sub ...201323555258
prevalence and trends of aminoglycoside resistance in shigella worldwide, 1999-2010.shigellosis causes diarrheal disease in humans in both developed and developing countries, and multi-drug resistance in shigella is an emerging problem. understanding changing resistance patterns is important in determining appropriate antibiotic treatments. this meta-analysis systematically evaluated aminoglycoside resistance in shigella. a systematic review was constructed based on medline and embase databases. random-effect models or fixed-effect models were used based on p value considering ...201323554801
characterization of the ospz promoter in shigella flexneri and its regulation by virb and h-ns.ospz is an effector protein of the type iii secretion system in shigella spp. that downregulates the human inflammatory response during bacterial infection. the ospz gene is located on the large virulence plasmid of shigella. many genes on this plasmid are transcriptionally repressed by the nucleoid structuring protein h-ns and derepressed by virb, a dna-binding protein that displays homology to the plasmid partitioning proteins parb and sopb. in this study, we characterized the ospz promoter an ...201323543709
structural basis for the recognition of ubc13 by the shigella flexneri effector ospi.ubc13 is a ubiquitin-conjugating enzyme that plays a key role in the nuclear factor-κb signal transduction pathway in human diseases. the shigella flexneri effector ospi affects inflammatory responses by catalyzing the deamidation of a specific glutamine residue at position 100 in ubc13 during infection. this modification prevents the activation of the tnf (tumor necrosis factor) receptor-associated factor 6, leading to modulation of the diacylglycerol-cbm (card-bcl10-malt1) complex-tnf receptor ...201323542009
topological investigation of glucosyltransferase v in shigella flexneri using the substituted cysteine accessibility method.modification of the lipopolysaccharide o-antigen of shigella converts the serotype, which is significant as acquired immune responses are serotype specific. glucosyltransferases (gtrs) modify the o-antigen by the addition of glucosyl-groups; however the precise mechanism of o-antigen modification is not fully understood. this study aims to substantiate inferences made on the gtrv topological structure using the substituted cysteine accessibility method (scam). twenty-one amino acid residues were ...201323534399
cefotaximase and ampc-producing shigella flexneri in case of dysentery from southern india.diarrhoea and dysentery caused by shigella spp. are major public health concerns. emerging multidrug resistance (mdr) in this pathogen further complicates this disease. extended spectrum β-lactamases (esbls) have been described in this pathogen, which significantly compromises the treatment options for shigellosis. the usual esbls seen are sulfhydryl variable (shv)-type; cefotaximases (ctx-m) are very uncommonly detected. here, we report a ctx-m type and ampc-producing shigella flexneri from a t ...201323508436
use of population-based surveillance to define the high incidence of shigellosis in an urban slum in nairobi, kenya.worldwide, shigella causes an estimated 160 million infections and >1 million deaths annually. however, limited incidence data are available from african urban slums. we investigated the epidemiology of shigellosis and drug susceptibility patterns within a densely populated urban settlement in nairobi, kenya through population-based surveillance.201323505506
[sensitivity to antibiotics and genetic support to resistance of shigella flexneri strains isolated in dakar from 2001 to 2010].diarrheal diseases remain a leading cause of death with 14.7 million deaths in 2001 and 26% of global mortality worldwide according to who. shigella species are prevalent in tropical areas; they are present all the year, with epidemic outbreaks in rainy season. between 2001 and 2010 one hundred ninety (190) strains of shigella flexneri isolated from national senegalese enterobacteriaceae center located at the pasteur institute in dakar were studied. susceptibility was performed by antibiogram fo ...201323483461
drug resistant shigella flexneri in & around dibrugarh, north-east india.shigella flexneri is the most common species of shigella causing diarrhoea and dysentery in asia including india. multidrug resistance in shigella species has been reported worldwide and there is rising concern regarding development of fluoroquinolone resistance. this study was undertaken to find out the resistance pattern of sh. flexneri, the commonest shigella isolated in dibrugarh, north east india, including detection of fluoroquinolone resistance and extended spectrum beta lactamases.201323481070
oligomeric states of the shigella translocator protein ipab provide structural insights into formation of the type iii secretion translocon.the shigella flexneri type iii secretion system (t3ss) senses contact with human intestinal cells and injects effector proteins that promote pathogen entry as the first step in causing life threatening bacillary dysentery (shigellosis). the shigella type iii secretion apparatus (t3sa) consists of an anchoring basal body, an exposed needle, and a temporally assembled tip complex. exposure to environmental small molecules recruits ipab, the first hydrophobic translocator protein, to the maturing t ...201323456854
[bacteraemia due to shigella flexneri serotype 6 in two patients with aids].infections due to shigella usually remain localized to the digestive tract and are self-limited. bacteremia is a potentially lethal complication that can occur in immunocompromised patients. we describe two episodes of bacteremia caused by shigella in two adults with aids. in both patients, s. flexneri was recovered from stool and blood samples. the isolates belonged to serotype 6, were resistant only to trimethoprim-sulfamethoxazole and showed a similar band profile by pulsed-field gel electrop ...201323450419
shigella in brazilian children with acute diarrhoea: prevalence, antimicrobial resistance and virulence genes.diarrhoeal disease is still considered a major cause of morbidity and mortality among children. among diarrhoeagenic agents, shigella should be highlighted due to its prevalence and the severity of the associated disease. here, we assessed shigella prevalence, drug susceptibility and virulence factors. faeces from 157 children with diarrhoea who sought treatment at the children's hospital joão paulo ii, a reference children´s hospital in belo horizonte, state of minas gerais, brazil, were cultur ...201323440111
shigella impairs t lymphocyte dynamics in vivo.the gram-negative enteroinvasive bacterium shigella flexneri is responsible for the endemic form of bacillary dysentery, an acute rectocolitis in humans. s. flexneri uses a type iii secretion system to inject effector proteins into host cells, thus diverting cellular functions to its own benefit. protective immunity to reinfection requires several rounds of infection to be elicited and is short-lasting, suggesting that s. flexneri interferes with the priming of specific immunity. considering the ...201323417297
transmission and strain variation of shigella flexneri 4a after mass prophylaxis in a long-stay psychiatric centre.shigella flexneri 4a caused sustained outbreaks in a large long-stay psychiatric centre, taiwan, 2001-2006. trimethoprim-sulphamethoxazole (sxt) prophylaxis was administered in 2004. we recovered 108 s. flexneri 4a isolates from 83 symptomatic (including one caregiver) and 12 asymptomatic subjects (11 contacts, one caregiver). the isolates were classified into eight antibiogram types and 15 genotypes (six clusters) by using antimicrobial susceptibility testing and pulsed-field gel electrophoresi ...201322364591
outer membrane protein a (ompa) of shigella flexneri 2a links innate and adaptive immunity in a tlr2-dependent manner and involvement of il-12 and nitric oxide.we determine that ompa of shigella flexneri 2a is recognized by tlr2 and consequently mediates the release of proinflammatory cytokines and activates nf-κb in hek 293 cells transfected with tlr2. we also observe that in raw macrophages tlr2 is essential to instigate the early immune response to ompa via nf-κb activation and secretion of cytokines and no. consistent with these results, tlr2 knockdown using sirna abolishes the initiation of immune responses. processing and presentation of ompa dep ...201222343631
emergence of resistance to fluoroquinolones and third-generation cephalosporins in shigella flexneri subserotype 1c isolates from china.we report here on the first identification of shigella flexneri subserotype 1c in china. we also report the emergence of resistance to ciprofloxacin and third-generation cephalosporins in this subserotype 1c for the first time. isolates of seven strains circulating in china yielded three new sequence types and seven pulsed-field gel electrophoresis patterns, thus demonstrating the existence of high genetic diversity within the isolates. overall, the seven isolates showed reduced susceptibility t ...201222329572
the structures of coiled-coil domains from type iii secretion system translocators reveal homology to pore-forming toxins.many pathogenic gram-negative bacteria utilize type iii secretion systems (t3sss) to alter the normal functions of target cells. shigella flexneri uses its t3ss to invade human intestinal cells to cause bacillary dysentery (shigellosis) that is responsible for over one million deaths per year. the shigella type iii secretion apparatus is composed of a basal body spanning both bacterial membranes and an exposed oligomeric needle. host altering effectors are secreted through this energized unidire ...201222321794
characterization of sfpgda, a shigella flexneri peptidoglycan deacetylase required for bacterial persistence within polymorphonuclear neutrophils.peptidoglycan deacetylases protect the gram-positive bacteria cell wall from host lysozymes by deacetylating peptidoglycan. sequence analysis of the genome of shigella flexneri predicts a putative polysaccharide deacetylase encoded by the plasmidic gene orf185, renamed here sfpgda. we demonstrated a peptidoglycan deacetylase (pgd) activity with the purified sfpgda in vitro. to investigate the role sfpgda in virulence, we constructed a sfpgda mutant and studied its phenotype in vitro. the mutant ...201222307019
an expert panel report of a proposed scientific model demonstrating the effectiveness of antibacterial handwash products.in 2005, a us food and drug administration nonprescription drug advisory committee (ndac) review of consumer antiseptic handwash product studies concluded that the data regarding existing products failed to demonstrate any association between specific log reductions of bacteria achieved by antiseptic handwashing and reduction of infection. the ndac recommended that consumer antibacterial handwashing products should demonstrate a reduction in infection compared with non-antibacterial handwash pro ...201222300895
interaction of mxig with the cytosolic complex of the type iii secretion system controls shigella virulence.gram-negative bacteria use the type 3 secretion system (t3ss) to colonize host cells. t3sss are ring-shaped macromolecular complexes specific for the transport of effector molecules into host cells. it was recently suggested that a cytosolic ring-shaped protein complex delivers effector molecules to the t3ss. however, how transport of effector proteins is regulated is not known. here, we report the high-resolution x-ray crystal structure of the whole cytosolic domain of mxig (mxig(1-126)), a maj ...201222247334
decreased susceptibility to antimicrobials among shigella flexneri isolates in manipal, south india--a 5 year hospital based study.shigellosis is endemic in many developing countries and an important cause of bloody diarrhea worldwide. our study was undertaken as a continuation of our earlier study during 2001 - 2006.the aim of this study was to monitor changes in shigella serogroups and resistance patterns to antimicrobials among shigella isolates. two thousand one hundred fecal samples were obtained from patients with diarrhea during june 2006-june 2011. isolates were identified by standard microbiological techniques as s ...201223413708
shigellosis outbreak associated with contaminated well water in a rural elementary school: sichuan province, china, june 7-16, 2009.we investigated a shigellosis outbreak in an elementary school to identify the source of infection, mode of transmission and risk factors for illness.201223071767
multi-locus sequence typing (mlst) and repetitive extragenic palindromic polymerase chain reaction (rep-pcr), characterization of shigella spp. over two decades in tianjin china.to understand the change of the dominant serogroup of shigella spp., their antimicrobial resistance over more than two decades in tianjin, their phylogenetic similarity and to determine their evolutionary biology by using rep-pcr and mlst in order to study their epidemiological character. multi-locus sequence typing was performed to determine their lineage and phylogenetic similarity. rep-pcr typing was used to study the homology of their genomic dna. the isolated rate of group d shigella in 200 ...201223205184
chromosomal and plasmid-encoded factors of shigella flexneri induce secretogenic activity ex vivo.shigella flexneri is a gram-negative, facultative intracellular pathogen that causes millions of cases of watery or bloody diarrhea annually, resulting in significant global mortality. watery diarrhea is thought to arise in the jejunum, and subsequent bloody diarrhea occurs as a result of invasion of the colonic epithelium. previous literature has demonstrated that shigella encodes enterotoxins, both chromosomally and on the 220 kilobase virulence plasmid. the shigellaenterotoxins 1 and 2 (shet1 ...201223166804
[calpain activation by shigella flexneri regulates key steps in the life and death of bacterium's epithelial niche]. 201223290392
analysis of different prognostic indicators for malnutrition and shigella flexneri infection among the children in bangladesh.the present study investigates into some socio-economic, demographic, and nutritional features that can predispose bangladeshi children to malnutrition and shigella flexneri infection. significant prognostic indicators associated with malnutrition were mother's illiteracy (unadjusted odds ratio, or = 2.580; 95% confidence interval, ci = 1.134-5.867 and adjusted odds ratio, ora, 3.814; 95% ci = 1.124-12.943), low birth weight (or = 3.143; 95% ci = 1.2-8.232 and ora = 2.404; 95% ci = 0.870-6.644) ...201223997331
quinolone-resistant shigella flexneri isolated in a patient who travelled to india.we report a recent case in which ciprofloxacin-resistant shigella flexneri was isolated from a 23-yr-old female patient with a history of travel to india. prior to her admission to our internal medicine department, she experienced symptoms of high fever and generalized weakness from continuous watery diarrhea that developed midway during the trip. s. flexneri was isolated from the stool culture. despite initial treatment with ciprofloxacin, the stool cultures continued to show s. flexneri growth ...201222950074
absence of o antigen suppresses shigella flexneri icsa autochaperone region mutations.the shigella flexneri icsa (virg) protein is a polarly distributed autotransporter protein. icsa functions as a virulence factor by interacting with the host actin regulatory protein n-wasp, which in turn activates the arp2/3 complex, initiating actin polymerization. formation of f-actin comet tails allows bacterial cell-to-cell spreading. although various accessory proteins such as periplasmic chaperones and the β-barrel assembly machine (bam) complex have been shown to be involved in the expor ...201222936034
identification of a divergent o-acetyltransferase gene oac 1b from shigella flexneri serotype 1b strains.shigella flexneri is a leading cause of bacterial dysentery in developing countries. among the 15 known serotypes, four (1b, 3a, 3b and 4b) contain a group 6 epitope due to an acetyl group connected to the o-2 position of rhamnose iii on the tetrasaccharide structure of the lipopolysaccharide. o-acetyltransferase encoded by a bacteriophage, sf6, mediates the acetylation reaction. we found that the oac gene in serotype 1b strains was very different from that in serotypes 3a, 3b and 4b strains and ...201226038428
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