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o-antigen modifications providing antigenic diversity of shigella flexneri and underlying genetic mechanisms.o-antigens (o-specific polysaccharides) of shigella flexneri, a primary cause of shigellosis, are distinguished by a wide diversity of chemical modifications following the oligosaccharide o-unit assembly. the present review is devoted to structural, serological, and genetic aspects of these modifications, including o-acetylation and phosphorylation with phosphoethanolamine that have been identified recently. the modifications confer the host with specific immunodeterminants (o-factors or o-antig ...201526542003
the multivalent adhesion molecule sso1327 plays a key role in shigella sonnei pathogenesis.shigella sonnei is a bacterial pathogen and causative agent of bacillary dysentery. it deploys a type iii secretion system to inject effector proteins into host epithelial cells and macrophages, an essential step for tissue invasion and immune evasion. although the arsenal of bacterial effectors and their cellular targets have been studied extensively, little is known about the prerequisites for deployment of type iii secreted proteins during infection. here, we describe a novel s. sonnei adhesi ...201626481305
invasive shigellosis in msm.shigella flexneri is an emerging pathogen in men who have sex with men (msm); recent outbreaks related to sexual practices have been noted in this population in the uk and other developed countries. while the majority of cases of shigellosis present with gastroenteritis, some vulnerable patients with underlying immunosuppression can develop complications like bacteraemia and may present atypically as an acute surgical emergency. this case report highlights such a case of s. flexneri bacteraemia ...201626429891
comparative proteomics of shigella flexneri 2a strain 301 using a rabbit ileal loop model reveals key proteins for bacterial adaptation in host niches.many studies focusing on changes in the host following shigella spp invasion have been reported in recent years. however, the key factors required for the adaptation of these pathogens to host niches have usually been neglected.201526417879
identification of shigella flexneri isolates carrying the shiga toxin 1-producing gene in quebec, canada, linked to travel to haiti. 201526401981
vasodilator-stimulated phosphoprotein restricts cell-to-cell spread of shigella flexneri at the cell periphery.shigella spp. are intracellular bacterial pathogens that cause diarrhoeal disease in humans. shigella utilize the host actin cytoskeleton to enter cells, move through the cytoplasm of cells and pass into adjacent cells. ena/vasp family proteins are highly conserved proteins that participate in actin-dependent dynamic cellular processes. we tested whether ena/vasp family members vasp (vasodilator-stimulated phosphoprotein), mena (mammalian-enabled) or evl (ena-vasp-like) contribute to shigella fl ...201526358985
shigellosis outbreak in al batinah south governorate, oman: case-control study.an outbreak of acute gastroenteritis due to shigella flexneri occurred in august 2012 in the catchment area of the wadi sahtan health center in rustaq, al batinah south governorate, oman. the aim of this study was to discover possible causes of this outbreak in the villages of fassa, rogh and amk and to measure the risk of exposure among cases and controls.201526357558
mechanism of action and initial, in vitro sar of an inhibitor of the shigella flexneri virulence regulator virf.shigella spp. are among the main causative agents of acute diarrheal illness and claim more than 1 million lives per year worldwide. there are multiple bacterial genes that control the pathogenesis of shigella, but the virf gene may be the most important. this gene, located on the primary pathogenicity island of shigella, encodes virf, an arac-family transcriptional activator that is responsible for initiating the pathogenesis cycle in shigella. we have previously shown that it is possible to at ...201526352269
investigation on the synthesis of shigella flexneri specific oligosaccharides using disaccharides as potential transglucosylase acceptor substrates.chemo-enzymatic strategies hold great potential for the development of stereo- and regioselective syntheses of structurally defined bioactive oligosaccharides. herein, we illustrate the potential of the appropriate combination of a planned chemo-enzymatic pathway and an engineered biocatalyst for the multistep synthesis of an important decasaccharide for vaccine development. we report the stepwise investigation, which led to an efficient chemical conversion of allyl α-d-glucopyranosyl-(1→4)-α-l- ...201526340432
a small conserved motif supports polarity augmentation of shigella flexneri icsa.the rod-shaped enteric intracellular pathogen shigella flexneri and other shigella species are the causative agents of bacillary dysentery. s. flexneri are able to spread within the epithelial lining of the gut, resulting in lesion formation, cramps and bloody stools. the outer membrane protein icsa is essential for this spreading process. icsa is the initiator of an actin-based form of motility whereby it allows the formation of a filamentous actin 'tail' at the bacterial pole. importantly, ics ...201526315462
determinants of proteolysis and cell-binding for the shigella flexneri cytotoxin, siga.shigella flexneri secretes an enterotoxic, spate family autotransporter (at), siga, which has cytopathic activity towards cultured epithelial cells. its cytopathic activity is due to its ability to degrade the cytoskeletal protein, α-fodrin. the mechanisms by which at toxins target cells and tissues differ and the details of how siga acts are not known. in the current study, the determinants of proteolysis and cell-targeting for siga were determined. we demonstrate that the siga passenger or α-d ...201526297175
detection of wzy/wzz interaction in shigella flexneri.the o antigen (oag) component of shigella flexneri lipopolysaccharide (lps) is important for virulence and a protective antigen. it is synthesized by the wzy-dependent mechanism. s. flexneri wzy has 12 transmembrane segments and two large periplasmic loops. the modal chain length of the oag is determined by wzz. experimental evidence supports multi-protein interactions in the wzy-dependent pathway. however, evidence for direct interaction of wzy with the other proteins of the wzy-dependent pathw ...201526296569
quantification of cytosolic vs. vacuolar salmonella in primary macrophages by differential permeabilization.intracellular bacterial pathogens can replicate in the cytosol or in specialized pathogen-containing vacuoles (pcvs). to reach the cytosol, bacteria like shigella flexneri and francisella novicida need to induce the rupture of the phagosome. in contrast, salmonella typhimurium replicates in a vacuolar compartment, known as salmonella-containing vacuole (scv). however certain mutants of salmonella fail to maintain scv integrity and are thus released into the cytosol. the percentage of cytosolic v ...201526274778
sting signaling the energic way.the effector proteins ipaj and vira, from the bacterium shigella flexneri, block the general secretory pathway (gsp) at different stages. in this issue of cell host & microbe, dobbs et al. (2015) use these proteins as a tool to pinpoint sting trafficking and signaling to the er-golgi intermediate compartment (ergic).201526269948
mutations in gyra & parc genes of shigella flexneri 2a determining the fluoroquinolone resistance. 201526205028
bacterial internalization, localization, and effectors shape the epithelial immune response during shigella flexneri infection.intracellular pathogens are differentially sensed by the compartmentalized host immune system. nevertheless, gene expression studies of infected cells commonly average the immune responses, neglecting the precise pathogen localization. to overcome this limitation, we dissected the transcriptional immune response to shigella flexneri across different infection stages in bulk and single cells. this identified six distinct transcriptional profiles characterizing the dynamic, multilayered host respo ...201526123804
hfq regulates acid tolerance and virulence by responding to acid stress in shigella flexneri.shigella flexneri is an important etiological agent of bacillary dysentery in developing countries. the hfq protein is thought to play a major regulatory role in various cellular processes in this organism. however, the roles of hfq in stress tolerance and virulence in s. flexneri in response to environmental stress have not been fully studied. in this study, hfq was highly expressed when s. flexneri was exposed to low ph. growth retardation was observed in the hfq deletion mutant at ph values r ...201526117597
clonal dissemination of a single shigella sonnei strain among iranian children during fall 2012 in tehran, i.r. iran.shigella species are a common cause of bacterial diarrhea worldwide and the disease is characterized by seasonality. shigella has been encountered by widespread resistance to commonly used antibiotics which is a serious concern. the aim of this study was to analyze the epidemiological relatedness of shigella strains isolated from children during one year period by pfge method and to investigate antimicrobial resistance determinants and cassettes among shigella species. the occurrence of shigella ...201526117443
bioimage analysis of shigella infection reveals targeting of colonic crypts.few studies within the pathogenic field have used advanced imaging and analytical tools to quantitatively measure pathogenicity in vivo. in this work, we present a novel approach for the investigation of host-pathogen processes based on medium-throughput 3d fluorescence imaging. the guinea pig model for shigella flexneri invasion of the colonic mucosa was used to monitor the infectious process over time with gfp-expressing s. flexneri. a precise quantitative imaging protocol was devised to follo ...201526056271
draft genomes of shigella strains used by the stopenterics consortium.despite a significant global burden of disease, there is still no vaccine against shigellosis widely available. one aim of the european union funded stopenterics consortium is to develop vaccine candidates against shigella. given the importance of translational vaccine coverage, here we aimed to characterise the shigella strains being used by the consortium by whole genome sequencing, and report on the stability of strains cultured in different laboratories or through serial passage.201526042182
antimicrobial resistance of shigella flexneri serotype 1b isolates in china.shigella flexneri serotype 1b is among the most prominent serotypes in developing countries, followed by serotype 2a. however, only limited data is available on the global phenotypic and genotypic characteristics of s. flexneri 1b. in the present study, 40 s. flexneri 1b isolates from different regions of china were confirmed by serotyping and biochemical characterization. antimicrobial susceptibility testing showed that 85% of these isolates were multidrug-resistant strains and antibiotic susce ...201526039698
shigella flexneri cell-to-cell spread, and growth and inflammation in mice, is limited by the outer membrane protease icsp.the shigella flexneri autotransporter protein icsa is essential for intra- and intercellular spread, and icsa mutants are attenuated in several models. however, the pathogenic significance of the outer membrane protease icsp, which orchestrates the polar distribution of icsa on the bacterial surface, remains unclear. to further examine this point, we constructed icsp mutants in the two most commonly studied s. flexneri strains and evaluated their in vitro and in vivo performance relative to wild ...201526025071
draft genome sequence of 24570, the type strain of shigella flexneri.shigella flexneri is a diarrheal pathogen that causes a large disease burden worldwide. we sequenced the genome of the publicly available type strain (s. flexneri 2a strain 24570) of this bacterial species to increase its utility as a reference. we present genome assembly results and comparisons with other reference strains.201526021915
escape of actively secreting shigella flexneri from atg8/lc3-positive vacuoles formed during cell-to-cell spread is facilitated by icsb and vira.the enteropathogenic bacterium shigella flexneri uses a type 3 secretion apparatus (t3sa) to transfer proteins dubbed translocators and effectors inside host cells, inducing bacterial uptake and subsequent lysis of the entry vacuole. once in the cytoplasm, the outer membrane protein icsa induces actin polymerization, enabling cytoplasmic movement and cell-to-cell spread of bacteria. during this infectious process, s. flexneri is targeted by atg8/lc3. the effector icsb was proposed to inhibit lc3 ...201526015503
prevalence and antimicrobial resistance of shigella flexneri serotype 2 variant in china.shigella flexneri serotype 2 variant (ii:3,4,7,8) was isolated in 2008 and first reported in china in 2013. in the present study, epidemiological surveillance from 2003 to 2013 in china suggested that this serotype first appeared in guangxi in 2003; it then emerged in shanghai and xinjiang in 2004 and in henan in 2008. of the 1813 s. flexneri isolates, 58 s. flexneri serotype 2 variant strains were identified. serotype 2 variant has emerged as a prominent serotype in recent years, with 2a (32.6% ...201525999941
effect of combination therapy between thyme oil and ciprofloxacin on ulcer-forming shigella flexneri.shigella flexneri is a gram-negative bacteria that has the ability to invade the epithelium of the colon and cause colon ulcers.201525989168
shigella flexneri: a cause of significant morbidity and associated with sexually transmitted infections in men who have sex with men. 201525970314
intensified shigellosis epidemic associated with sexual transmission in men who have sex with men--shigella flexneri and s. sonnei in england, 2004 to end of february 2015.surveillance data suggest an intensification of the shigellosis epidemic associated with sexual transmissionin men who have sex with men (msm) in england with separate introductions into the population. in 2014, sexual transmission between msm might have accounted for 97%, 89%, and 43% of non-travel associated shigella flexneri 3a and s. flexneri 2a, ands. sonnei diagnoses. clinicians should sensitively ascertain sexual history for men with enteric infections to facilitate prompt diagnosis and a ...201525953129
intercontinental dissemination of azithromycin-resistant shigellosis through sexual transmission: a cross-sectional study.shigellosis is an acute, severe bacterial colitis that, in high-income countries, is typically associated with travel to high-risk regions (africa, asia, and latin america). since the 1970s, shigellosis has also been reported as a sexually transmitted infection in men who have sex with men (msm), in whom transmission is an important component of shigellosis epidemiology in high-income nations. we aimed to use sophisticated subtyping and international sampling to determine factors driving shigell ...201525936611
shigella flexneri serotype 3a: the rise of a superbug. 201525936610
sex, drugs and smart phone applications: findings from semistructured interviews with men who have sex with men diagnosed with shigella flexneri 3a in england and wales.to inform control strategies undertaken as part of an outbreak of shigella flexneri 3a among men who have sex with men (msm).201525921020
clinical and microbiological profiles of shigellosis in children.shigellosis presents with varied clinical features are dictated by the species involved, virulence factors of the strain, and the host immune status. we studied the species, virulence genes, and antibiotic susceptibility pattern of the shigella strains isolated from 33 children aged less than 12 years, with clinical features of shigellosis. identification and antibiotic sensitivity of shigella species were done using disc diffusion and e-test. multiplex pcr was done for the detection of virulenc ...201425895190
the passenger-associated transport repeat promotes virulence factor secretion efficiency and delineates a distinct autotransporter subtype.autotransporters are a superfamily of virulence factors secreted by gram negative bacteria. they are comprised of an n-terminal passenger domain that is translocated across the outer membrane and a c-terminal domain that inserts into the outer membrane forming a β-barrel anchor. it is still poorly understood how the passenger is efficiently translocated in the absence of external energy inputs. several mechanisms have been proposed in solution of this problem, yet due to the vast diversity of si ...201525869731
enhanced resistance to fluoroquinolones in laboratory-grown mutants & clinical isolates of shigella due to synergism between efflux pump expression & mutations in quinolone resistance determining region.there is a worldwide emergence of fluoroquinolone resistance in shigella species. to understand the molecular mechanisms associated with fluoroquinolone resistance, naturally occurring fluoroquinolone-resistant strains and laboratory-induced spontaneous mutants of shigella spp. were used and the relative contributions of acrab-tolc efflux pumps, gyrase and topoisomerase target gene mutations towards fluoroquinolone resistance were determined.201525857499
myosin-x and disease.myosin-x (myo10) is a motor protein best known for its role in filopodia formation. new research implicates myo10 in a number of disease states including cancer metastasis and pathogen infection. this review focuses on these developments with emphasis on the emerging roles of myo10 in formation of cancer cell protrusions and metastasis. a number of aggressive cancers show high levels of myo10 expression and knockdown of myo10 has been shown to dramatically limit cancer cell motility in 2d and 3d ...201525819274
key residues of s. flexneri ompa mediate infection by bacteriophage sf6.many viruses, including bacteriophage, have the inherent ability to utilize several types of proteinaceous receptors as an attachment mechanism to infect cells, yet the molecular mechanisms that drive receptor binding have not been elucidated. using bacteriophage sf6 and its host, shigella flexneri, we investigated how sf6 utilizes outer membrane protein a (ompa) for infection. specifically, we identified that surface loops of ompa mediate shigella infection. we further characterized which resid ...201525816773
shigella flexneri: a three-year antimicrobial resistance monitoring of isolates in a children hospital, ahvaz, iran.shigellosis is an acute gastroenteritis that is one of the most common causes of morbidity and mortality in children with diarrhea in developing countries. the purpose of this study was to describe the distribution of shigella serogroups and serotypes and their antibacterial drug resistance profiles.201425802704
myristoylome profiling reveals a concerted mechanism of arf gtpase deacylation by the bacterial protease ipaj.n-myristoylation is an essential fatty acid modification that governs the localization and activity of cell signaling enzymes, architectural proteins, and immune regulatory factors. despite its importance in health and disease, there are currently no methods for reversing protein myristoylation in vivo. recently, the shigella flexneri protease ipaj was found to cleave myristoylated glycine of eukaryotic proteins, yet the discriminatory mechanisms of substrate selection required for targeted demy ...201525773595
shigella flexneri regulation of arf6 activation during bacterial entry via an ipgd-mediated positive feedback loop.entry into cells is critical for virulence of the human bacterial pathogens shigella spp. shigella spp. induce membrane ruffle formation and macropinocytic uptake, but the events instigating this process are incompletely understood. the host small gtpase adp-ribosylation factor 6 (arf6) functions in membrane trafficking at the plasma membrane and activates membrane ruffle formation. we demonstrate that arf6 is required for efficient shigella flexneri entry, is activated by s. flexneri dependent ...201525736891
aa479 antiserum: new reagent for the serotype characterization of atypical variants of shigella flexneri.shigella flexneri is divided into 13 serotypes based on the combination of antigenic determinants present in the o-antigen. a new o-antigen modification with phosphoethanolamine has been identified. the presence of this antigenic determinant (called e1037) is recognized by monoclonal antibody masf iv-1. given the increasing incidence of these new variants and the difficulty in supplying the monoclonal antibody to our country, we produced a polyclonal antiserum (aa479) through immunization with a ...201525735215
shift in serotype distribution of shigella species in china, 2003-2013.we identified 2912 shigella isolates from diarrhoeal patients in china during 2003-2013. the most common species was shigella flexneri (55.3%), followed by shigella sonnei (44.1%); however, s. sonnei is becoming increasingly prevalent. among the s. flexneri isolates, serotypes 2a and x variant (-:7,8, e1037) were the two most prevalent serotypes, and serologically atypical isolates were also commonly identified. overall, s. sonnei, s. flexneri 2a and s. flexneri x variant (-:7,8, e1037) accounte ...201525658535
shigella flexneri serotype 1 infections in men who have sex with men in vancouver, canada.outbreaks of shigellosis have been documented in men who have sex with men (msm), associated with interpersonal transmission and underlying hiv infection. we observed a rise in shigella flexneri isolates identified in a downtown tertiary-care hospital laboratory located within the city centre community health area (cha-1) of vancouver, canada. the objectives of this study were to evaluate clinical outcomes of shigellosis cases among msm admitted to hospital and to evaluate trends in shigella cas ...201525656740
a large outbreak of shigellosis commencing in an internally displaced population, papua new guinea, 2013.the objective of this study was to investigate a large outbreak of shigellosis in papua new guinea that began in a camp for internally displaced persons before spreading throughout the general community.201425648967
mutational analysis of the major periplasmic loops of shigella flexneri wzy: identification of the residues affecting o antigen modal chain length control, and wzz-dependent polymerization activity.the o antigen (oag) component of lps is a major shigella flexneri virulence determinant. oag is polymerized by wzysf, and its modal chain length is determined by wzzsf and wzzphs2. site-directed mutagenesis was performed on wzysf in pwaldo-wzysf-tev-gfp to alter arg residues in wzysf's two large periplasmic loops (pls) (pl3 and pl5). analysis of the lps profiles conferred by mutated wzysf proteins in the wzysf deficient (δwzy) strain identified residues that affect wzysf activity. the importance ...201525627441
specific 13c labeling of leucine, valine and isoleucine methyl groups for unambiguous detection of long-range restraints in protein solid-state nmr studies.here we present an isotopic labeling strategy to easily obtain unambiguous long-range distance restraints in protein solid-state nmr studies. the method is based on the inclusion of two biosynthetic precursors in the bacterial growth medium, α-ketoisovalerate and α-ketobutyrate, leading to the production of leucine, valine and isoleucine residues that are exclusively (13)c labeled on methyl groups. the resulting spectral simplification facilitates the collection of distance restraints, the verif ...201525625825
genetic characterization of shigella flexneri isolates in guizhou province, china.shigella flexneri is one of the major etiologic causes of shigellosis in guizhou province, china. however, the genetic characteristics of circulating isolates are unknown. phenotypic and molecular profiles of 60 s. flexneri isolates recovered in guizhou between 1972 to 1982 and 2008 to 2010 were determined. nine serotypes (1a, 2a, 3a, 1b, 2b, x, y, 4av and yv) were identified. multi-locus sequence typing differentiated the isolates into 20 sequence types (sts); 18 were novel. four sts, st 129, s ...201525617838
overexpression, purification, crystallization and preliminary x-ray crystallographic analysis of sf173 from shigella flexneri.shigella flexneri is a gram-negative, anaerobic bacterium in the genus shigella that can cause diarrhoea in humans. sf173, a hypothetical protein from s. flexneri 5a strain m90t, has been cloned, overexpressed, purified and crystallized as a part of laboratory-scale structural genomics project. the sf173 protein was crystallized using the sitting-drop vapour-diffusion method in the presence of 0.8 m succinic acid ph 7.0 at 293 k. preliminary x-ray diffraction analysis revealed that the crystal d ...201525615969
tom1 is a pi5p effector involved in the regulation of endosomal maturation.phosphoinositides represent a major class of lipids specifically involved in the organization of signaling cascades, maintenance of the identity of organelles and regulation of multiple intracellular trafficking steps. we previously reported that phosphatidylinositol 5-monophosphate (pi5p), produced by the shigella flexneri phosphatase ipgd, is implicated in the endosomal sorting of the epidermal growth factor receptor (egfr). here, we show that the adaptor protein tom1 is a new direct binding p ...201525588840
comparison of resistance to third-generation cephalosporins in shigella between europe-america and asia-africa from 1998 to 2012.we conducted a systematic review to compare resistance to third-generation cephalosporins (tgcs) in shigella strains between europe-america and asia-africa from 1998 to 2012 based on a literature search of computerized databases. in asia-africa, the prevalence of resistance of total and different subtypes to ceftriaxone, cefotaxime and ceftazidime increased markedly, with a total prevalence of resistance up to 14·2% [95% confidence interval (ci) 3·9-29·4], 22·6% (95% ci 4·8-48·6) and 6·2% (95% c ...201525553947
targeting of chromatin readers: a novel strategy used by the shigella flexneri virulence effector ospf to reprogram transcription.shigella flexneri, a gram-negative bacterium responsible of bacillary dysentery, uses multiple strategies to overcome host immune defense. we have decrypted how this bacterium manipulates host-cell chromatin binders to take control of immune gene expression. we found that ospf, an injected virulence factor previously identified as a repressor of immune gene expression, targets the chromatin reader hp1γ. heterochromatin protein 1 family members specifically recognize and bind histone h3 methylate ...201428357260
outbreak of locally acquired azithromycin-resistant shigella flexneri infection in men who have sex with men. 201525474524
structural characterization of a flexible two-domain protein in solution using small angle x-ray scattering and nmr data.multidomain proteins in which individual domains are connected by linkers often possess inherent interdomain flexibility that significantly complicates their structural characterization in solution using either nuclear magnetic resonance (nmr) spectroscopy or small-angle x-ray scattering (saxs) alone. here, we report a protocol for joint refinement of flexible multidomain protein structures against nmr distance and angular restraints, residual dipolar couplings, and saxs data. the protocol is ba ...201425456817
comparative proteomic analysis of outer membrane vesicles from shigella flexneri under different culture conditions.the production of outer membrane vesicles (omvs) is a common and regulated process of gram-negative bacteria. nonetheless, the processes of shigella flexneri omv production still remain unclear. s. flexneri is the causative agent of endemic shigellosis in developing countries. the congo red binding of strains is associated with increased infectivity of s. flexneri. therefore, understanding the modulation pattern of omv protein expression induced by congo red will help to elucidate the bacterial ...201425445584
the extant world war 1 dysentery bacillus nctc1: a genomic analysis.shigellosis (previously bacillary dysentery) was the primary diarrhoeal disease of world war 1, but outbreaks still occur in military operations, and shigellosis causes hundreds of thousands of deaths per year in developing nations. we aimed to generate a high-quality reference genome of the historical shigella flexneri isolate nctc1 and to examine the isolate for resistance to antimicrobials.201425441199
the shigella flexneri ospb effector: an early immunomodulator.through the action of the type three secretion system (t3ss) shigella flexneri delivers several effectors into host cells to promote cellular invasion, multiplication and to exploit host-cell signaling pathways to modulate the host innate immune response. although much progress has been made in the understanding of many type iii effectors, the molecular and cellular mechanism of the ospb effector is still poorly characterized. in this study we present new evidence that better elucidates the role ...201525434600
the shigella flexneri type 3 secretion system is required for tyrosine kinase-dependent protrusion resolution, and vacuole escape during bacterial dissemination.shigella flexneri is a human pathogen that triggers its own entry into intestinal cells and escapes primary vacuoles to gain access to the cytosolic compartment. as cytosolic and motile bacteria encounter the cell cortex, they spread from cell to cell through formation of membrane protrusions that resolve into secondary vacuoles in adjacent cells. here, we examined the roles of the type 3 secretion system (t3ss) in s. flexneri dissemination in ht-29 intestinal cells infected with the serotype 2a ...201425405985
update on molecular epidemiology of shigella infection.shigella spp. are important etiologic agents of diarrhea worldwide. this review summarizes the recent findings on the epidemiology, diagnosis, virulence genes, and pathobiology of shigella infection.201525394237
time-resolved assembly of a nucleoprotein complex between shigella flexneri virf promoter and its transcriptional repressor h-ns.the virf gene of shigella, responsible for triggering the virulence cascade in this pathogenic bacterium, is transcriptionally repressed by the nucleoid-associated protein h-ns. the primary binding sites of h-ns within the promoter region of virf have been detected here by footprinting experiments in the presence of h-ns or its monomeric dna-binding domain (h-nsctd), which displays the same specificity as intact h-ns. of the 14 short dna fragments identified, 10 overlap sequences similar to the ...201425389261
genome assembly of shigella flexneri atcc 12022, a quality control reference strain.shigella flexneri causes shigellosis, severe and potentially life-threatening diarrhea, and accounts for 18% of shigellosis cases in the united states. here, we present the 4.51-mbp genome assembly of s. flexneri atcc 12022, a quality control and reference strain, in 10 scaffolds.201425359907
genetic and structural identification of an o-acyltransferase gene (oacc) responsible for the 3/4-o-acetylation on rhamnose iii in shigella flexneri serotype 6.o-antigen (o-polysaccharide) of the lipopolysaccharide is a highly variable cell component of the outer membrane in shigella flexneri. it defines the serospecificity and plays an important role in the pathogenesis of shigellosis. there are two distinct o-antigen forms for the 19 serotypes of s. flexneri: one for serotypes 1-5, x, y, 7 (and their subtypes), and the other for serotype 6. although having different basal o-polysaccharide structures, the two forms share a common disaccharide fragment ...201425327486
transcriptional adaptation of shigella flexneri during adherence to epithelial cells.shigella adhesion to host cells is a transitional stage from an extracellular to an intracellular environment. however, the dynamic adaptations of shigella during adhesion are poorly understood. to address this, we performed the first transcriptome analysis of shigella flexneri 2457t during adhesion. a total of 1,757 genes were differentially regulated (>twofold). the majority of plasmid-borne ipa-mxi-spa locus genes were downregulated, indicating these virulence genes were strictly regulated af ...201525291620
outer membrane protein a (ompa) of shigella flexneri 2a induces tlr2-mediated activation of b cells: involvement of protein tyrosine kinase, erk and nf-κb.b cells are critically important in combating bacterial infections and their differentiation into plasma cells and memory cells aids bacterial clearance and long-lasting immunity conferred by essentially all vaccines. outer membrane protein a (ompa) of shigella flexneri 2a has been demonstrated to induce the production of igg and iga in vivo following immunization of mice through intranasal route, but the direct involvement of b cells in ompa-mediated immune regulation was not determined. conseq ...201425286253
high-resolution structure of the shigella type-iii secretion needle by solid-state nmr and cryo-electron microscopy.we introduce a general hybrid approach for determining the structures of supramolecular assemblies. cryo-electron microscopy (cryo-em) data define the overall envelope of the assembly and rigid-body orientation of the subunits while solid-state nuclear magnetic resonance (ssnmr) chemical shifts and distance constraints define the local secondary structure, protein fold and inter-subunit interactions. finally, rosetta structure calculations provide a general framework to integrate the different s ...201425264107
[shigella flexneri bacteremia, one adult case and review of the literature]. 201425229381
use of shigella flexneri to study autophagy-cytoskeleton interactions.shigella flexneri is an intracellular pathogen that can escape from phagosomes to reach the cytosol, and polymerize the host actin cytoskeleton to promote its motility and dissemination. new work has shown that proteins involved in actin-based motility are also linked to autophagy, an intracellular degradation process crucial for cell autonomous immunity. strikingly, host cells may prevent actin-based motility of s. flexneri by compartmentalizing bacteria inside 'septin cages' and targeting them ...201425226510
an optofluidic imaging system to measure the biophysical signature of single waterborne bacteria.in this paper, for the first time, an on-chip optofluidic imaging system is innovated to measure the biophysical signatures of single waterborne bacteria, including both their refractive indices and morphologies (size and shape), based on immersion refractometry. the key features of the proposed optofluidic imaging platform include (1) multiple sites for single-bacterium trapping, which enable parallel measurements to achieve higher throughput, and (2) a chaotic micromixer, which enables efficie ...201425205636
detection and analysis of crisprs of shigella.the recently discovered crisprs (clustered regularly interspaced short palindromic repeats) and cas (crispr-associated) proteins are a novel genetic barrier that limits horizontal gene transfer in prokaryotes and the crispr loci provide a historical view of the exposure of prokaryotes to a variety of foreign genetic elements. the aim of study was to investigate the occurrence and distribution of the crisprs in shigella. a collection of 61 strains of shigella were screened for the existence of cr ...201525199561
shigella flexneri infection in caenorhabditis elegans: cytopathological examination and identification of host responses.the gram-negative bacterium shigella flexneri is the causative agent of shigellosis, a diarrhoeal disease also known as bacillary dysentery. s. flexneri infects the colonic and rectal epithelia of its primate host and induces a cascade of inflammatory responses that culminates in the destruction of the host intestinal lining. molecular characterization of host-pathogen interactions in this infection has been challenging due to the host specificity of s. flexneri strains, as it strictly infects h ...201425187942
effect of sodium chloride on the survival of shigella flexneri in acidified laboratory media and cucumber puree.this study investigated the effects of sodium chloride (nacl) and various acids, alone or in combination, on shigella flexneri growth in laboratory medium and cucumber puree.201425178712
serotype-conversion in shigella flexneri: identification of a novel bacteriophage, sf101, from a serotype 7a strain.shigella flexneri is the major cause of bacillary dysentery in the developing countries. the lipopolysaccharide (lps) o-antigen of s. flexneri plays an important role in its pathogenesis and also divides s. flexneri into 19 serotypes. all the serotypes with an exception for serotype 6 share a common o-antigen backbone comprising of n-acetylglucosamine and three rhamnose residues. different serotypes result from modification of the basic backbone conferred by phage-encoded glucosyltransferase and ...201425174528
linear synthesis of the branched pentasaccharide repeats of o-antigens from shigella flexneri 1a and 1b demonstrating the major steric hindrance associated with type-specific glucosylation.shigella flexneri serotypes 1b and 1a are gram-negative enteroinvasive bacteria causing shigellosis in humans. the o-antigen from s. flexneri 1b is a { → 2)-[3ac/4ac]-α-l-rhap-(1 → 2)-α-l-rhap-(1 → 3)-[2ac]-α-l-rhap-(1 → 3)-[α-d-glcp-(1 → 4)]-β-d-glcpnac-(1 → }n branched polysaccharide ({(ac)ab(ac)c(e)d}n). it is identical to that from s. flexneri 1a, except for the 2c-acetate. a concise synthesis of the disaccharide ed, trisaccharides (ac)c(e)d and c(e)d, tetrasaccharides b(ac)c(e)d and bc(e)d, ...201425141906
multidrug resistant shigella flexneri : a rare case of septicemia in an infant.shigellosis is still an important public health problem in developing and under-developed countries. it may lead to rare but potentially fatal various extra intestinal complications like septicemia, involvement of cns, urinary tract and liver especially in young malnourished children. the disease is difficult to prevent as only few bacteria are required for causing infection and there is increasing infection with multi drug resistant strains. a 6-month-old infant developed septicemia caused by m ...201425120984
the serine/threonine kinase stk11 promotes shigella flexneri dissemination through establishment of cell-cell contacts competent for tyrosine kinase signaling.shigella flexneri is an intracellular pathogen that disseminates in the intestinal epithelium by displaying actin-based motility. we found that although s. flexneri displayed comparable actin-based motilities in the cytosols of hela229 and ht-29 epithelial cell lines, the overall dissemination process was much more efficient in ht-29 cells. time-lapse microscopy demonstrated that as motile bacteria reached the cell cortex in ht-29 cells, they formed membrane protrusions that resolved into vacuol ...201425114112
influence of oligomerization state on the structural properties of invasion plasmid antigen b from shigella flexneri in the presence and absence of phospholipid membranes.shigella flexneri causes bacillary dysentery, an important cause of mortality among children in the developing world. shigella secretes effector proteins via its type iii secretion system (t3ss) to promote bacterial uptake into human colonic epithelial cells. the t3ss basal body spans the bacterial cell envelope anchoring a surface-exposed needle. a pentamer of invasion plasmid antigen d lies at the nascent needle tip and invasion plasmid antigen b (ipab) is recruited into the needle tip complex ...201425103195
sumoylation controls host anti-bacterial response to the gut invasive pathogen shigella flexneri.shigella flexneri, the etiological agent of bacillary dysentery, invades the human colonic epithelium and causes its massive inflammatory destruction. little is known about the post-translational modifications implicated in regulating the host defense pathway against shigella. here, we show that sumo-2 impairs shigella invasion of epithelial cells in vitro. using mice haploinsufficient for the sumo e2 enzyme, we found that sumoylation regulates intestinal permeability and is required to restrict ...201425097252
bid-dependent release of mitochondrial smac dampens xiap-mediated immunity against shigella.the x-linked inhibitor of apoptosis protein (xiap) is a potent caspase inhibitor, best known for its anti-apoptotic function in cancer. during apoptosis, xiap is antagonized by smac, which is released from the mitochondria upon caspase-mediated activation of bid. recent studies suggest that xiap is involved in immune signaling. here, we explore xiap as an important mediator of an immune response against the enteroinvasive bacterium shigella flexneri, both in vitro and in vivo. our data demonstra ...201425056906
draft genome sequence of a new shigella flexneri subserotype, 4s bj10610.shigella flexneri is of great concern in the prevalence of shigellosis and resistance to many antibiotics in developing countries. here, we report the draft genome sequence of a new s. flexneri subserotype, 4s bj10610, isolated from the stool specimens of a patient in beijing, china.201425035336
fluoroquinolone resistance mechanisms of shigella flexneri isolated in bangladesh.to investigate the prevalence and mechanisms of fluoroquinolone resistance in shigella species isolated in bangladesh and to compare with similar strains isolated in china.201425028972
middle-down mass spectrometry enables characterization of branched ubiquitin chains.protein ubiquitylation, one of the most prevalent post-translational modifications in eukaryotes, is involved in regulating nearly every cellular signaling pathway. the vast functional range of ubiquitylation has largely been attributed to the formation of a diverse array of polymeric ubiquitin (polyub) chains. methods that enable the characterization of these diverse chains are necessary to fully understand how differences in structure relate to function. here, we describe a method for the dete ...201425023374
transfer patterns of integron-associated and antibiotic resistance genes in s. flexneri during different time intervals in tianjin, china.shigella is one of the common genera of pathogens responsible for bacterial diarrhoea in humans. according to world health organisation (who), 800,000-1,700,000 patients in china were infected with shigella spp. in 2000, and shigella flexneri is the most common serotype (86%).201425008817
structural basis for lipopolysaccharide insertion in the bacterial outer membrane.one of the fundamental properties of biological membranes is the asymmetric distribution of membrane lipids. in gram-negative bacteria, the outer leaflet of the outer membrane is composed predominantly of lipopolysaccharides (lps). the export of lps requires seven essential lipopolysaccharide transport (lpt) proteins to move lps from the inner membrane, through the periplasm to the surface. of the seven lpt proteins, the lptd-lpte complex is responsible for inserting lps into the external leafle ...201424990751
myosin iia is essential for shigella flexneri cell-to-cell spread.a key feature of shigella pathogenesis is the ability to spread from cell-to-cell post-invasion. this is dependent on the bacteria's ability to initiate de novo f-actin tail polymerisation, followed by protrusion formation, uptake of bacteria-containing protrusion and finally, lysis of the double membrane vacuole in the adjacent cell. in epithelial cells, cytoskeletal tension is maintained by the actin-myosin ii networks. in this study, the role of myosin ii and its specific kinase, myosin light ...201424989342
shigella reroutes host cell central metabolism to obtain high-flux nutrient supply for vigorous intracellular growth.shigella flexneri proliferate in infected human epithelial cells at exceptionally high rates. this vigorous growth has important consequences for rapid progression to life-threatening bloody diarrhea, but the underlying metabolic mechanisms remain poorly understood. here, we used metabolomics, proteomics, and genetic experiments to determine host and shigella metabolism during infection in a cell culture model. the data suggest that infected host cells maintain largely normal fluxes through glyc ...201424958876
reconstituted human polyclonal plasma-derived secretory-like igm and iga maintain the barrier function of epithelial cells infected with an enteropathogen.intravenous administration of polyclonal and monoclonal antibodies has proven to be a clinically valid approach in the treatment, or at least relief, of many acute and chronic pathologies, such as infection, immunodeficiency, and a broad range of autoimmune conditions. plasma-derived igg or recombinant igg are most frequently used for intravenous or subcutaneous administration, whereas a few igm-based products are available as well. we have established recently that secretory-like iga and igm ca ...201424951593
atypical haemolytic uraemic syndrome associated with a cd46 mutation triggered by shigella flexneri.we present a case of haemolytic uraemic syndrome (hus) triggered by shigella flexneri. of the shigella species, only s. dysenteriae type 1 is said to produce shiga toxin and consequently cause hus. investigation of the complement system in this patient revealed a cd46 mutation. in individuals with mutations in complement genes incomplete penetrance of atypical hus (ahus) is seen, suggesting that a trigger, such as infection, is required for disease to manifest. in an era of complement modulatory ...201424944786
elongation factor p and modifying enzyme poxa are necessary for virulence of shigella flexneri.elongation factor p (ef-p) is a universally conserved bacterial translation factor. in many bacteria, ef-p is posttranslationally modified by poxa, which covalently attaches a β-lysine to a conserved lysine residue of ef-p. here we show that both ef-p and poxa are necessary for virulence of the human diarrheal pathogen shigella flexneri. loss of either ef-p or poxa leads to an impaired ability of s. flexneri to invade epithelial cells and form plaques in an epithelial cell monolayer. proteomic a ...201424935977
travel-related shigellosis in quebec, canada: an analysis of risk factors.travel-related shigellosis is not well documented in canada although it is frequently acquired abroad and can cause severe disease.201524889090
shigella flexneri inhibits intestinal inflammation by modulation of host sphingosine-1-phosphate in mice.infection with invasive shigella species results in intestinal inflammation in humans but no symptoms in adult mice. to investigate why adult mice are resistant to invasive shigellae, 6~8-week-old mice were infected orally with s. flexneri 5a. shigellae successfully colonized the small and large intestines. mild cell death was seen but no inflammation. the infected bacteria were cleared 24 hours later. microarray analysis of infected intestinal tissue showed that several genes that are involved ...201424851099
non-stoichiometric o-acetylation of shigella flexneri 2a o-specific polysaccharide: synthesis and antigenicity.synthetic functional mimics of the o-antigen from shigella flexneri 2a are seen as promising vaccine components against endemic shigellosis. herein, the influence of the polysaccharide non-stoichiometric di-o-acetylation on antigenicity is addressed for the first time. three decasaccharides, representing relevant internal mono- and di-o-acetylation profiles of the o-antigen, were synthesized from a pivotal protected decasaccharide designed to tailor late stage site-selective o-acetylation. the l ...201424836582
genetic characterization of shigella spp. isolated from diarrhoeal and asymptomatic children.phenotypic and genetic characteristics of shigella spp. isolated from diarrhoeal and asymptomatic children aged up to 5 years were analysed in this study. in total, 91 and 17 isolates were identified from diarrhoeal (case) and asymptomatic (control) children, respectively. all the isolates were tested for antimicrobial resistance, the presence of integrons, plasmid-mediated quinolone resistance (pmqr), virulence-associated genes and shigella pathogenicity island (sh-pai). the majority of the shi ...201424790083
dynamin-related protein drp1 and mitochondria are important for shigella flexneri infection.shigella infection in epithelial cells induces cell death which is accompanied by mitochondrial dysfunction. in this study the role of the mitochondrial fission protein, drp1 during shigella infection in hela cells was examined. significant lactate dehydrogenase (ldh) release was detected in the culture supernatant when hela cells were infected with shigella at a high multiplicity of infection. drp1 inhibition with mdivi-1 and sirna knockdown significantly reduced ldh release. hela cell death wa ...201424755420
role of intracellular carbon metabolism pathways in shigella flexneri virulence.shigella flexneri, which replicates in the cytoplasm of intestinal epithelial cells, can use the embden-meyerhof-parnas, entner-doudoroff, or pentose phosphate pathway for glycolytic carbon metabolism. to determine which of these pathways is used by intracellular s. flexneri, mutants were constructed and tested in a plaque assay for the ability to invade, replicate intracellularly, and spread to adjacent epithelial cells. mutants blocked in the embden-meyerhof-parnas pathway (pfkab and pykaf mut ...201424733092
icsa is a shigella flexneri adhesin regulated by the type iii secretion system and required for pathogenesis.following contact with the epithelium, the enteric intracellular bacterial pathogen shigella flexneri invades epithelial cells and escapes intracellular phagosomal destruction using its type iii secretion system (t3ss). the bacterium replicates within the host cell cytosol and spreads between cells using actin-based motility, which is mediated by the virulence factor icsa (virg). whereas s. flexneri invasion is well characterized, adhesion mechanisms of the bacterium remain elusive. we found tha ...201424721572
draft genome sequences of the type strains of shigella flexneri held at public health england: comparison of classical phenotypic and novel molecular assays with whole genome sequence.public health england (phe) holds a collection of shigella flexneri type strains isolated between 1949 and 1972 representing 15 established serotypes and one provisional type, e1037. in this study, the genomes of all 16 phe type strains were sequenced using the illumina hiseq platform. the relationship between core genome phylogeny and serotype was examined.201424684748
ompa and ompc are critical host factors for bacteriophage sf6 entry in shigella.despite being essential for successful infection, the molecular cues involved in host recognition and genome transfer of viruses are not completely understood. bacterial outer membrane proteins a and c co-purify in lipid vesicles with bacteriophage sf6, implicating both outer membrane proteins as potential host receptors. we determined that outer membrane proteins a and c mediate sf6 infection by dramatically increasing its rate and efficiency. we performed a combination of in vivo studies with ...201424673644
serological identification and prevalence of a novel o-antigen epitope linked to 3- and 4-o-acetylated rhamnose iii of lipopolysaccharide in shigella flexneri.shigella flexneri is the major cause of shigellosis in developing countries. all serotypes except for serotype 6 share an o-antigen backbone composed of a → 2)-α-l-rhap(iii)-(1 → 2)-α-l-rhap(ii)-(1 → 3)-α-l-rhap(i)-(1 → 3)-β-d-glcpnac-(1 → tetrasaccharide repeat. it can be modified by the addition of a glucosyl group to one or more sugar residues and/or an o-acetyl group to rha(i) and/or a phosphoethanolamine to rha(ii) and/or rha(iii). these modifications give rise to type i-, ic-, ii-, iv-, an ...201424671799
tyrosine kinases, drugs, and shigella flexneri dissemination.shigella flexneri is an enteropathogenic bacterium responsible for approximately 100 million cases of severe dysentery each year. s. flexneri colonization of the human colonic epithelium is supported by direct spread from cell to cell, which relies on actin-based motility. we have recently uncovered that, in intestinal epithelial cells, s. flexneri actin-based motility is regulated by the bruton's tyrosine kinase (btk). consequently, treatment with ibrutinib, a specific btk inhibitor currently u ...201724637806
new insights into the crosstalk between shigella and t lymphocytes.subversion of host immune responses is the key infection strategy employed by most, if not all, human pathogens. modulation of the host innate response by pathogens has been vastly documented. yet, especially for bacterial infections, it was only recently that cells of the adaptive immune response were recognized as targets of bacterial weapons such as the type iii secretion system (t3ss) and its effector proteins. in this review, we focus on the recent advances made in the understanding of how ...201424613405
conformational diversity of o-antigen polysaccharides of the gram-negative bacterium shigella flexneri serotype y.o-antigen polysaccharides constitute the outer protective layer of most gram-negative bacteria, important for the bacterium's survival and adaption within its host. although important for many functions, the three-dimensional structure of the dense polysaccharide coat remains to be elucidated. in this study, we present a systematic numerical investigation of o-antigen polysaccharide chains of shigella flexneri serotype y composed of one up to four tetrasaccharide repeat units. to bridge the gap ...201424559142
potential novel antibiotics from hts targeting the virulence-regulating transcription factor, virf, from shigella flexneri.virf is an arac-type transcriptional regulator responsible for activating the transcription of virulence genes required for the intracellular invasion and cell-to-cell spread of shigella flexneri. gene disruption studies have validated virf as a potential target for an anti-virulence therapy to treat shigellosis by determining that virf is necessary for virulence, but not required for bacterial viability. using a bacteria-based, β-galactosidase reporter assay we completed a high-throughput scree ...201424549153
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