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a fluorescent reporter reveals on/off regulation of the shigella type iii secretion apparatus during entry and cell-to-cell spread.numerous pathogenic gram-negative bacteria use a type three secretion apparatus (t3sa) to translocate effector proteins into host cells. detecting and monitoring the t3sa of intracellular bacteria within intact host cells has been challenging. taking advantage of the tight coupling between t3s effector-gene transcription and t3sa activity in shigella flexneri, together with a fast-maturing green fluorescent protein, we developed reporters to monitor t3sa activity in real time. these reporters re ...201424528864
oral administration of live shigella vaccine candidates in rhesus monkeys show no evidence of competition for colonization and immunogenicity between different serotypes.live oral monovalent shigella flexneri 2a vaccine candidates as well as bivalent formulations with shigella sonnei were evaluated in a rhesus monkey model for colonization and immunogenicity. freshly harvested suspensions of s. flexneri 2a vaccine candidates wrsf2g12 and wrsf2g15 as well as s. sonnei vaccine candidate wrss3 were nasogastrically administered to groups of rhesus monkeys, macaca mulatta, either in a monovalent form or when combined with each other. the animals were monitored daily ...201424522159
shigellemia in a post renal transplant patient: a case report and literature review.shigellemia is a complication of shigellosis that occurs generally in malnourished children. in adults, shigellemia is usually seen in immunocompromised individuals. here we report the first case of shigellemia in a renal transplant patient from india. the patient had history of diarrhea, which was treated symptomatically. subsequently, the patient developed high-grade fever and blood culture was positive for shigella flexneri. recovery was uneventful after the initiation of antimicrobial therap ...201424518636
identification of an o-acyltransferase gene (oacb) that mediates 3- and 4-o-acetylation of rhamnose iii in shigella flexneri o antigens.o antigen (o polysaccharide) is an important and highly variable cell component present on the surface of cells which defines the serospecificity of gram-negative bacteria. most o antigens of shigella flexneri, a cause of shigellosis, share a backbone composed of →2)-α-l-rhap(iii)-(1→2)-α-l-rhap(ii)-(1→3)-α-l-rhap(i)-(1→3)-β-d-glcpnac-(1→ repeats, which can be modified by adding various substituents, giving rise to 19 serotypes. the known modifications include glucosylation on various sugar resi ...201424509314
case of shigella flexneri infection with treatment failure due to azithromycin resistance in an hiv-positive patient. 201424488332
the vps/vacj abc transporter is required for intercellular spread of shigella flexneri.the vps/vacj abc transporter system is proposed to function in maintaining the lipid asymmetry of the outer membrane. mutations in vps or vacj in shigella flexneri resulted in increased sensitivity to lysis by the detergent sodium dodecyl sulfate (sds), and the vpsc mutant showed minor differences in its phospholipid profile compared to the wild type. vpsc mutants were unable to form plaques in cultured epithelial cells, but this was not due to a failure to invade, to replicate intracellularly, ...201424478081
a substrate-fusion protein is trapped inside the type iii secretion system channel in shigella flexneri.the type iii secretion system (t3ss) is a macromolecular complex used by gram-negative bacteria to secrete effector proteins from the cytoplasm across the bacterial envelope in a single step. for many pathogens, the t3ss is an essential virulence factor that enables the bacteria to interact with and manipulate their respective host. a characteristic structural feature of the t3ss is the needle complex (nc). the nc resembles a syringe with a basal body spanning both bacterial membranes and a long ...201424453973
genomic portrait of the evolution and epidemic spread of a recently emerged multidrug-resistant shigella flexneri clone in china.shigella flexneri is the major cause of shigellosis in developing countries. a new s. flexneri serotype, xv, appeared in 2000 and replaced serotype 2a as the most prevalent serotype in china. serotype xv is a variant of serotype x, with phosphoethanolamine modification of its o antigen mediated by a plasmid that contained the opt gene. serotype xv isolates belong to sequence type 91 (st91). in this study, whole-genome sequencing of 59 s. flexneri isolates of 14 serotypes (serotypes 1 to 4, y, yv ...201424452172
plasmid-mediated sulfamethoxazole resistance encoded by the sul2 gene in the multidrug-resistant shigella flexneri 2a isolated from patients with acute diarrhea in dhaka, bangladesh.in this study, mechanisms of plasmid-mediated sulfamethoxazole resistances in the clinical strains of multi-drug resistant (mdr) shigella flexneri 2a were elucidated for the first time in bangladesh. from 2006 to 2011, a total of 200 s. flexneri 2a strains were randomly selected from the stock of the enteric and food microbiology laboratory of icddr,b. antimicrobial susceptibility of the strains showed 73%, 98%, 93%, 58%, 98%, 64% and 4% resistance to trimethoprim-sulfamethoxazole, nalidixic aci ...201424416393
effect of wild-type shigella species and attenuated shigella vaccine candidates on small intestinal barrier function, antigen trafficking, and cytokine release.bacterial dysentery due to shigella species is a major cause of morbidity and mortality worldwide. the pathogenesis of shigella is based on the bacteria's ability to invade and replicate within the colonic epithelium, resulting in severe intestinal inflammatory response and epithelial destruction. although the mechanisms of pathogenesis of shigella in the colon have been extensively studied, little is known on the effect of wild-type shigella on the small intestine and the role of the host respo ...201424416363
development and preclinical evaluation of a trivalent, formalin-inactivated shigella whole-cell vaccine.studies were undertaken to manufacture a multivalent shigella inactivated whole-cell vaccine that is safe, effective, and inexpensive. by using several formalin concentrations, temperatures, and incubation periods, an optimized set of inactivation conditions was established for shigella flexneri 2a, s. sonnei, and s. flexneri 3a to produce inactivated whole cells expressing a full repertoire of ipa proteins and lipopolysaccharide (lps). the inactivation conditions selected were treatment with 0. ...201424403527
dissemination and serotype modification potential of psfxv_2, an o-antigen petn modification plasmid in shigella flexneri.the o-antigens of all shigella flexneri serotypes, except serotype 6, share a linear tetrasaccharide repeat composed of one n-acetylglucosamine and three l-rhamnose residues, and differences between the serotypes are due to modification of various monosaccharide residues with glucosyl and/or o-acetyl and/or phosphoethanolamine (petn) groups. plasmid-borne opt (formerly lpt-o) gene encoding a petn transferase which modifies the o-antigens of s. flexneri serotype x, 4a and y strains and converts t ...201424379081
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
enhanced type iii secretion system expression of atypical shigella flexneri ii:(3)4,7(8).we aimed at evaluating the virulence of atypical shigella flexneri ii:(3)4,7(8) by dna microarray and invasion assay.201224159518
spa13 of shigella flexneri has a dual role: chaperone escort and export gate-activator switch of the type iii secretion system.the type iii secretion apparatus (t3sa) is used by numerous gram-negative pathogens to inject virulence factors into eukaryotic cells. the shigella flexneri t3sa spans the bacterial envelope and its assembly requires the products of ~20 mxi and spa genes. despite progress made in understanding how the t3sa is assembled, the role of several predicted soluble components, such as spa13, remains elusive. here, we show that the secretion defect of the spa13 mutant is associated with lack of t3sa asse ...201424126350
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
shigella flexneri enteritis in risk-taking hiv-infected msm. 201424055803
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
hypoxic stress, hepatocytes and caco-2 viability and susceptibility to shigella flexneri invasion.inflammation due to shigella flexneri can cause damage to the colonic mucosa and cell death by necrosis and apoptosis. this bacteria can reach the bloodstream in this way, and the liver through portal veins. hypoxia is a condition present in many human diseases, and it may induce bacterial translocation from intestinal lumen. we studied the ability of s. flexneri to invade rat hepatocytes and caco-2 cells both in normoxic and hypoxic microenvironments, as well as morphological and physiological ...201524037289
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
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
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
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
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
[calpain activation by shigella flexneri regulates key steps in the life and death of bacterium's epithelial niche]. 201223290392
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
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
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
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
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
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
shigella flexneri bacteremia in adult. 201222923931
molecular profiling of antimicrobial resistance and integron association of multidrug-resistant clinical isolates of shigella species from faisalabad, pakistan.bacillary dysentery, common in developing countries, is usually caused by shigella species. a major problem in shigellosis is the rapid emergence of multidrug-resistant strains. this is the first detailed molecular study on drug resistance of shigella isolates from the faisalabad region of pakistan. ninety-five shigella isolates obtained after screening of 2500 stool samples were evaluated for in vitro resistance to commonly used antimicrobial agents; the presence or absence of 20 of the most re ...201222906205
bacterial secretion and the role of diffusive and subdiffusive first passage processes.by funneling protein effectors through needle complexes located on the cellular membrane, bacteria are able to infect host cells during type iii secretion events. the spatio-temporal mechanisms through which these events occur are however not fully understood, due in part to the inherent challenges in tracking single molecules moving within an intracellular medium. as a result, theoretical predictions of secretion times are still lacking. here we provide a model that quantifies, depending on the ...201222879888
emergence of a novel shigella flexneri serotype 1d in china.we report on the isolation of 5 shigella flexneri strains displaying a novel serotype, 1d, that shares serologic features from both s. flexneri serotypes 1a and x. the 1d strains contained serotype-converting bacteriophages sfi and sfx in tandem on the chromosome. these strains were likely originated from serotype x strains through sfi infection.201222858548
characterization of lipid a profiles from shigella flexneri variant x lipopolysaccharide.in developing countries, shigella flexneri (sf) is the major causative agent of the endemic shigellosis (bacillary dysentery) responsible annually for one million fatalities mostly among infants. lipopolysaccharides (lpss) are characteristic components of the outer membrane of the overwhelming majority of gram-negative bacteria. since lipid a is essential for the viability of the gram-negative bacteria, it is subject to extensive chemical studies with new analytical techniques.201222847700
virb-mediated positive feedback control of the virulence gene regulatory cascade of shigella flexneri.shigella flexneri is a facultative intracellular pathogen that relies on a type iii secretion system and its associated effector proteins to cause bacillary dysentery in humans. the genes that encode this virulence system are located on a 230-kbp plasmid and are transcribed in response to thermal, osmotic, and ph signals that are characteristic of the human lower gut. the virulence genes are organized within a regulatory cascade, and the nucleoid-associated protein h-ns represses each of the key ...201222821978
[analysis of etiological surveillance results of shigella spp between 2009 and 2010 in henan province].to explore the etiologic characteristics of bacillary dysentery found in henan province, between year 2009 and 2010.201222800632
[multilocus variable-number tandem-repeat analysis for molecular subtypes of shigella isolates in beijing].selecting variable-number tandem-repeat (vntr) loci for different serogroups of shigella spp to explore and establish multilocus variable-number tandem-repeat analysis (mlva) method, in order to study the molecular characteristic of the isolated strains.201222800631
identification of critical residues of the serotype modifying o-acetyltransferase of shigella flexneri.thirteen serotypes of shigella flexneri (s. flexneri) have been recognised, all of which are capable of causing bacillary dysentery or shigellosis. with the emergence of the newer s. flexneri serotypes, the development of an effective vaccine has only become more challenging. one of the factors responsible for the generation of serotype diversity is an lps o-antigen modifying, integral membrane protein known as o-acetyltransferase or oac. oac functions by adding an acetyl group to a specific o-a ...201222793174
molecular dynamics simulations of carbohydrate-mimetic haptens in complex with a complementary anti-carbohydrate antibody.the monoclonal antibody sya/j6 is specific for the o-polysaccharide of the shigella flexneri y bacterium. two haptens, a pentasaccharide and a mimetic octapeptide, bind to sya/j6 with moderate binding affinities. in a previous attempt to obtain improved binding affinity to sya/j6, two glycopeptide chimeras (α-glycopeptide and β-glycopeptide) were designed based on the structures of the pentasaccharide and the octapeptide, as well as a molecular docking study. despite the overall fit of the ligan ...201222789717
shigella flexneri bacteremia in two immune-competent adult travelers.shigella bacteremias are uncommon in immune-competent adults. we report two cases of shigella flexneri bacteremia that occurred in healthy young travelers, who recovered. self-medication with loperamide and ibuprofen without antibiotics (case 1) and concomitant falciparum malaria (case 2) were the only co-morbidities found in our two patients.201222776390
[construction of prokaryotic expression vectors for tandem affinity purification].to construct prokaryotic expression vectors suitable for tandem affinity purification to study protein-protein interactions in bacteria.201222712409
the normal chain length distribution of the o antigen is required for the interaction of shigella flexneri 2a with polarized caco-2 cells.shigella flexneri causes bacillary dysentery in humans. essential to the establishment of the disease is the invasion of the colonic epithelial cells. here we investigated the role of the lipopolysaccharide (lps) o antigen in the ability of s. flexneri to adhere to and invade polarized caco-2 cells. the s. flexneri 2a o antigen has two preferred chain lengths: a short o antigen (s-oag) regulated by the wzzb protein and a very long o antigen (vl-oag) regulated by wzz phs2. mutants with defined de ...201222688980
nlrp10 enhances shigella-induced pro-inflammatory responses.members of the nlr family evolved as intracellular sensors for bacterial and viral infection. however, our knowledge on the implication of most of the human nlr proteins in innate immune responses still remains fragmentary. here we characterized the role of human nlrp10 in bacterial infection. our data revealed that nlrp10 is a cytoplasmic localized protein that positively contributes to innate immune responses induced by the invasive bacterial pathogen shigella flexneri. sirna-mediated knock-do ...201222672233
two live attenuated shigella flexneri 2a strains wrsf2g12 and wrsf2g15: a new combination of gene deletions for 2nd generation live attenuated vaccine candidates.shigella infections are a major cause of inflammatory diarrhea and dysentery worldwide. first-generation virg-based live attenuated shigella strains have been successfully tested in phase i and ii clinical trials and are a leading approach for shigella vaccine development. additional gene deletions in sena, senb and msbb2 have been engineered into second-generation virg-based shigella flexneri 2a strains producing wrsf2g12 and wrsf2g15. both strains harbor a unique combination of gene deletions ...201222658966
roles of h2 uptake hydrogenases in shigella flexneri acid tolerance.hydrogenases play many roles in bacterial physiology, and use of h(2) by the uptake-type enzymes of animal pathogens is of particular interest. hydrogenases have never been studied in the pathogen shigella, so targeted mutant strains were individually generated in the two shigella flexneri h(2)-uptake enzymes (hya and hyb) and in the h(2)-evolving enzyme (hyc) to address their roles. under anaerobic fermentative conditions, a hya mutant strain (hya) was unable to oxidize h(2), while a hyb mutant ...201222628482
[development of a singleplex pcr assay targeting o-antigen modification genes for molecular serotyping of shigella flexneri].to develop a singleplex pcr assay targeting o-antigen modification genes for molecular serotyping of shigella (s.) flexneri.201222613389
antimicrobial susceptibility patterns of shigella isolates in foodborne diseases active surveillance network (foodnet) sites, 2000-2010.treatment of shigellosis with appropriate antimicrobial agents shortens duration of illness and bacterial shedding, but resistance to commonly used agents is increasing.201222572670
genome sequence of shigella flexneri serotype 5a strain m90t sm.bacteria of the genus shigella are a major cause of death worldwide (l. von seidlein et al., plos med. 3:e353, 2006). we sequenced the genome of shigella flexneri strain m90t sm (serotype 5a) and compared it to the published genome sequence of s. flexneri strain 8401 (serotype 5b).201222582379
shigella flexneri effectors ospe1 and ospe2 mediate induced adherence to the colonic epithelium following bile salts exposure.shigella flexneri is a gram-negative pathogen that invades the colonic epithelium. while invasion has been thoroughly investigated, it is unknown how shigella first attaches to the epithelium. previous literature suggests that shigella utilizes adhesins that are induced by environmental signals, including bile salts, encountered in the small intestine prior to invasion. we hypothesized that bile would induce adherence factors to facilitate attachment to colonic epithelial cells. to test our hypo ...201222571618
prevalence of plasmid-mediated quinolone resistance determinants in association with β-lactamases, 16s rrna methylase genes and integrons amongst clinical isolates of shigella flexneri. 201222556328
hierarchies of host factor dynamics at the entry site of shigella flexneri during host cell invasion.shigella flexneri, the causative agent of bacillary dysentery, induces massive cytoskeletal rearrangement, resulting in its entry into nonphagocytic epithelial cells. the bacterium-engulfing membrane ruffles are formed by polymerizing actin, a process activated through injected bacterial effectors that target host small gtpases and tyrosine kinases. once inside the host cell, s. flexneri escapes from the endocytic vacuole within minutes to move intra- and intercellularly. we quantified the fluor ...201222526677
self-association of the shigella flexneri icsa autotransporter protein.the icsa autotransporter protein is a major virulence factor of the human intracellular pathogen shigella flexneri. icsa is distributed at the poles in the outer membrane (om) of s. flexneri and interacts with components of the host actin-polymerization machinery to facilitate intracellular actin-based motility and subsequent cell-to-cell spreading of the bacterium. we sought to characterize the biochemical properties of icsa in the bacterial om. chemical cross-linking data suggested that icsa e ...201222516224
standardization and international multicenter validation of a pulsenet pulsed-field gel electrophoresis protocol for subtyping shigella flexneri isolates.shigella flexneri is one of the agents most frequently linked to diarrheal illness in developing countries and often causes outbreaks in settings with poor hygiene or sanitary conditions. travel is one of the means by which s. flexneri can be imported into developed countries, where this pathogen is not commonly seen. a robust and discriminatory subtyping method is needed for the surveillance of s. flexneri locally and regionally, and to aid in the detection and investigation of outbreaks. the p ...201222506731
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