Publications

TitleAbstractYear
Filter
PMID
Filter
shigellosis in nepal: 13 years review of nationwide surveillance.shigella is a major cause of gastroenteritis especially in children. in developing countries, the incidence is frequent and results are often life threatening. changing epidemiology and emerging antibiotic resistance warrants continuous monitoring of susceptibility. the present study highlights the changing epidemiology and drug resistance patterns of shigella isolated at different hospitals of nepal over a period of 13 years (jan. 2003-dec. 2015).201627814742
a review on sero diversity and antimicrobial resistance patterns of shigella species in africa, asia and south america, 2001-2014.shigella, gram negative bacterium, is responsible for shigellosis/bacillary dysentery. it is a global concern although it predominates in developing countries. these are shigella dysenteriae, shigella flexneri, shigella boydii and shigella sonnei. drug resistance by shigella species is another headache of the world. therefore; this study aimed to review distribution of shigella serogroups and their antimicrobial patterns carried out in africa, asia and south america.201627576729
molecular characterisation of quinolone-resistant shigella strains isolated in tehran, iran.over the past few years, the number of shigella strains resistant to nalidixic acid has increased and has made the selection of effective antimicrobial therapy more difficult. the purpose of this study was to investigate the molecular mechanism of quinolone resistance in shigella strains. shigella strains isolated from 1100 diarrhoeal patients in tehran, iran, were assessed for their susceptibility to nalidixic acid prior to pcr-rflp and sequence analysis of their quinolone resistance genes. amo ...201627436462
intracellular and membrane-damaging activities of methyl gallate isolated from terminalia chebula against multidrug-resistant shigella spp.shigella spp. (shigella dysenteriae, shigella flexneri, shigella boydii and shigella sonnei) cause bacillary dysentery (shigellosis), which is characterized by bloody mucous diarrhoea. although a variety of antibiotics have been effective for treatment of shigellosis, options are becoming limited due to globally emerging drug resistance. in the present study, in vitro antibacterial activity of methyl gallate (mg) isolated from terminalia chebula was determined by performing mic, minimal bacteric ...201526272388
shigella outer membrane protein pssp-1 is broadly protective against shigella infection.in developing countries, shigella is a primary cause of diarrhea in infants and young children. although antibiotic therapy is an effective treatment for shigellosis, therapeutic options are narrowing due to the emergence of antibiotic resistance. thus, preventive vaccination could become the most efficacious approach for controlling shigellosis. we have identified several conserved protein antigens that are shared by multiple shigella serotypes and species. among these, one antigen induced cros ...201525651919
molecular characterization of serologically atypical provisional serovars of shigella isolates from kolkata, india.during 2000-2004, 13 shigella strains that were untypable by commercially available antisera were isolated from children <5 years of age with acute diarrhoea in kolkata. these strains were subsequently identified as shigella dysenteriae provisional serovar 204/96 (n = 3), shigella dysenteriae provisional serovar e23507 (n = 1), shigella dysenteriae provisional serovar i9809-73 (n = 1), shigella dysenteriae provisional serovar 93-119 (n = 1), shigella flexneri provisional serovar 88-893 (n = 6) a ...201425261061
isolation and development of bioluminescent reporter phages for bacterial dysentery.shigellosis is a significant cause of morbidity and mortality worldwide, most notably amongst children. moreover, there is a global increase in the occurrence of multidrug-resistant isolates, including the epidemic and pandemic shigella dysenteriae type 1 strain. we developed a bioluminescent reporter phage assay to facilitate detection and simultaneously determine antibiotic susceptibility. a shigella flexneri phage (shfl25875) was isolated from environmental wastewater and characterized by dna ...201525252629
protective immunity by oral immunization with heat-killed shigella strains in a guinea pig colitis model.the protective efficacy of and immune response to heat-killed cells of monovalent and hexavalent mixtures of six serogroups/serotypes of shigella strains (shigella dysenteriae 1, shigella flexneri 2a, s. flexneri 3a, s. flexneri 6, shigella boydii 4, and shigella sonnei) were examined in a guinea pig colitis model. a monovalent or hexavalent mixture containing 1 × 10(7) of each serogroup/serotype of heat-killed shigella cells was administered orally on days 0, 7, 14 and 21. on day 28, the immuni ...201324033533
characterization and complete genome sequence of the shigella bacteriophage psf-1.shigellosis is a global health problem, and shigella flexneri is the major cause of this disease. in this study, we isolated a virulent siphoviridae bacteriophage (phage), psf-1, that infects s. flexneri. this phage was isolated from the han river in korea and was found to infect s. flexneri, shigella boydii, and shigella sonnei. one-step growth analysis revealed that this phage has a short latent period (10 min) and a large burst size (86.86 pfu/cell), indicating that psf-1 has good host infect ...201324012542
multi-serotype outer membrane vesicles of shigellae confer passive protection to the neonatal mice against shigellosis.recently, we have demonstrated, immunization of adult female mice with outer membrane vesicles (omvs) of shigella boydii type 4 protected their offspring passively from shigellosis. in our present study, we have advanced our research by formulating multi-serotype outer membrane vesicles (momvs), mixing the omvs of shigella dysenteriae 1 δstx, shigella flexneri 2a, 3a and 6, s. boydii type 4 and shigella sonnei to achieve a broad spectrum protection against shigellosis. adult mice were immunized ...201323684822
phage inactivation of foodborne shigella on ready-to-eat spiced chicken.shigellosis, also called bacillary dysentery, is an infectious disease caused by shigella species, including shigella flexneri, shigella dysenteriae, shigella sonnei, and shigella boydii. infection with s. flexneri can result in epidemics, and shigella-contaminated food is often the source of infection, such as ready-to-eat spiced chicken and duck. therefore, we investigated the ability of shigella phages to inhibit pathogenic shigella spp. in ready-to-eat spiced chicken. food samples were inocu ...201323243250
studies on shigella boydii infection in caenorhabditis elegans and bioinformatics analysis of immune regulatory protein interactions.shigella boydii causes bacillary dysentery or shigellosis and generates a significant burden in the developing nations. s. boydii-mediated infection assays were performed at both physiological and molecular levels using caenorhabditis elegans as a host. continuous exposure of worms to s. boydii showed a reduced life span indicating the pathogenicity of shigella. quantitative real-time pcr analysis was performed to analyze the expression and regulation of host specific candidate-antimicrobial gen ...201222841995
outer membrane vesicles of shigella boydii type 4 induce passive immunity in neonatal mice.like most other gram-negative bacteria, shigella releases outer membrane vesicles (omvs) into the surrounding environment during growth. in this study, we have exploited omvs of shigella as a protective immunogen in a mice model against shigellosis. distinctive vesicle secretion was noticed from different shigella strains. among them, shigella boydii type 4 (bch612) was secreting relatively higher amounts. we immunized female adult mice orally with 32 μg of purified shigella boydii type 4 (bch61 ...201222762732
effect of bovine lactoferrin on the minimum inhibitory concentrations of ampicillin and trimethoprim-sulfamethoxazole for clinical shigella spp. strains.here, we determined the effect of bovine lactoferrin (blf) on the minimum inhibitory concentration (mic) of ampicillin and trimethoprim-sulfamethoxazole in shigella . using a microdilution method, the mic was determined in the presence or absence of bovine lactoferrin (10 mg/ml) on 88 shigella strains (56 shigella flexneri , 15 shigella boydii , 13 shigella sonnei , and 4 shigella dysenteriae ) previously isolated from peruvian children <2 years old. a fold change of 2 or more in mic values was ...201222397495
antimicrobial-resistant shigella infections from iran: an overlooked problem?in this study, we wanted to assess the level of antimicrobial resistance, the presence of genes encoding resistance to cephalosporins and plasmid-mediated quinolone resistance (pmqr), and genetic relatedness among shigella isolates obtained from iranian patients.201222345385
[point-of-care tests for the rapid diagnosis of shigellosis].worldwide, it is estimated that 140 million people suffer from shigellosis annually. the traditional identification of shigella spp. by culture lacks sensitivity. rapid diagnosis of shigellosis is important because it allows to engage appropriate antimicrobial treatment that shortens the duration and severity of the illness and reduces microbial carriage, thus the spread of infection in the community. onestep immunochromatographic dipstick tests have been successfully developed at institut paste ...201728116567
molecular characterization of multidrug-resistant shigella spp. of food origin.shigella spp. are the causative agents of food-borne shigellosis, an acute enteric infection. the emergence of multidrug-resistant clinical isolates of shigella presents an increasing challenge for clinicians in the treatment of shigellosis. several studies worldwide have characterized the molecular basis of antibiotic resistance in clinical shigella isolates of human origin, however, to date, no such characterization has been reported for shigella spp. of food origin. in this study, we characte ...201525485847
shigella: a highly virulent and elusive pathogen.despite a significant decrease in shigella-related mortality, shigellosis continues to carry a significant burden of disease worldwide, particularly in asia and africa. shigella is a highly virulent pathogen comprised of four major species with numerous subtypes. shigella dysenteriae and shigella flexneri infections are predominant in resource-limited settings. clinical presentations range from mild watery diarrhea to severe dysentery with systemic complications such as electrolyte imbalance, se ...201425110633
molecular cloning and biologically active production of ipad n-terminal region.shigella is known as pathogenic intestinal bacteria in high dispersion and pathogenic bacteria due to invasive plasmid antigen (ipa). so far, a number of ipa proteins have been studied to introduce a new candidate vaccine. here, for the first time, we examined whether the n-terminal region of ipad(72-162) could be a proper candidate for shigella vaccine. initially, the dna sequence coding n-terminal region was isolated by pcr from shigella dysenteriae type i and cloned into pet-28a expression ve ...201323731655
multiplexed immunoassay to assess shigella-specific antibody responses.infection with shigella spp. results in bacillary dysentery and a systemic and mucosal antibody response. the immune response is directed at multiple antigens, including lps and the invasin plasmid antigen (ipa) proteins, and is capable of conferring short-term, serotype-specific protection. both live-attenuated and several subunit vaccine approaches have focused on inducing a pronounced mucosal immune response directed to the same antigens recognized after natural infection. traditionally, shig ...201323583496
cephalosporin-resistant shigella flexneri over 9 years (2001-09) in india.to determine the pattern and antimicrobial resistance genes of cephalosporin resistance in shigella flexneri and shigella dysenteriae over 9 years.201222410619
antimicrobial effects of psidium guajava extract as one mechanism of its antidiarrhoeal action.a morphine-like spasmolytic action (not naloxone reversible; involving the inhibition of acetylcholine release) and also effects on the transmural transport of electrolytes (na(+) and k(+)) and water have been reported as possible modes of the antidiarrhoeal action of polar fractions of psidium guajava leaf extractives. the objective for this study was to verify if the reported modes of the antidiarrhoeal action should be broadened to include direct antimicrobial actions on some of the more comm ...199922589684
[stability of changed properties of streptomycin-resistant strain of shigella flexneri after prolonged preservation]. 201424544446
analysis of shigella flexneri resistance, biofilm formation, and transcriptional profile in response to bile salts.the shigella species cause millions of cases of watery or bloody diarrhea each year, mostly in children in developing countries. while many aspects of shigella colonic cell invasion are known, crucial gaps in knowledge remain regarding how the bacteria survive, transit, and regulate gene expression prior to infection. in this study, we define mechanisms of bile salts resistance and build on previous research highlighting induced virulence in s. flexneri strain 2457t following bile salts exposure ...201728348056
double-stranded rna induces cathelicidin expression in the intestinal epithelial cells through phosphatidylinositol 3-kinase-protein kinase cζ-sp1 pathway and ameliorates shigellosis in mice.cathelicidin antimicrobial peptide is a key component of the host innate immune system. it is constitutively expressed by the intestinal epithelial cells, but induced at further higher levels by different host-derived and microbial stimuli, including the ligands for toll-like receptors (tlrs). while the underlying mechanisms of cathelicidin expression remain incompletely understood, altered expression may be associated with gastro-intestinal infections and inflammatory diseases. we demonstrate h ...201728343946
shigellosis caused by ctx-m type esbl producing shigella flexneri in two siblings of rural nepal: first case report from the country.shigellosis is an acute infectious disease characterized as severe bloody diarrhea (dysentery) and is accountable for a significant burden of morbidity and mortality especially in children under the age of 5 years. antimicrobial therapy is required in the cases of severe dysentery associated with shigella. however, emergence of multidrug resistant (mdr) strains of shigella spp. over the last two decades has restricted the use of common therapeutic antimicrobials. in mdr strains, the third-genera ...201728321350
structural insights into the architecture of the shigella flexneri virulence factor icsa/virg and motifs involved in polar distribution and secretion.icsa/virg is a key virulence factor of the human pathogen shigella flexneri, acting as both an adhesin and actin-polymerizing factor during infection. we identified a soluble expression construct of the icsa/virg α-domain using the esprit library screening system and determined its structure to 1.9å resolution. in addition to the previously characterized autochaperone domain, our structure reveals a new domain, which shares a common fold with the autochaperone domains of various autotransporters ...201728268178
quantitative analysis of shigella flexneri protein expression under acid stress.as an important foodborne pathogen, shigella flexneri can cause widespread enteric infection with bacteria as few as hundreds. this is, at least in part, attributed to its robust anti-acid strategies because passage through the highly acidic human digestive tract is a prerequisite for successful bacterial infection. nevertheless, our understanding of these mechanisms and the impact of acid stress on shigella protein expression still remains largely incomplete. herein we conducted a proteomic sur ...201728221718
an outbreak of shigellosis in a children welfare institute caused by a multiple-antibiotic-resistant strain of shigella flexneri 2a.from september 1 to october 27, 2015, an outbreak of bacillary dysentery occurred in the shenzhen children welfare institute (scwi). the shigellosis was uncommon in shenzhen and no related outbreak was reported during the last 5 years. an epidemiological investigation was conducted and the children and nursing workers in scwi were surveyed for gastrointestinal symptoms; 28 of children reported having a diarrheal illness. rectal swabs or fecal specimens from 14 case patients and 24 nursing worker ...201728189512
multi-locus sequence type analysis of shigellas pp. isolates from tehran, iran.strains of shigella spp. can cause shigellosis, or bacillary dysentery. that is a public health problem worldwide. the aim of this study was to describe the population structure and genetic relatedness of multidrug resistant s. sonnei and s. flexneri isolated during a one year period from children with diarrhea in tehran, iran.201628149488
azithromycin-nonsusceptible shigella flexneri 3a in men who have sex with men, taiwan, 2015-2016.we report an outbreak of azithromycin-nonsusceptible shigella flexneri 3a infection in taiwan associated with men who have sex with men. the bacterial strains belonged to the sublineage a of a recently reported outbreak lineage associated with men who have sex with men, characterized by reduced azithromycin susceptibility and circulation in shigellosis low-risk regions.201628098533
[epidemiology and etiology of bacillary dysentery in xinjiang uigur autonomous region, 2004-2014].objective: to understand the epidemiological and etiological characteristics of bacillary dysentery in xinjiang uigur autonomous region (xinjiang) during 2004-2014, and provide evidence for the prevention and control of bacillary dysentery. methods: descriptive epidemiological analysis was conducted by using the incidence data of bacillary dysentery in xinjiang during 2004-2014 and the serotyping and the antibiotic susceptibility test of the pathogens isolated were performed. results: a total of ...201628072950
iridoids from canthium subcordatum iso-butanol fraction with potent biological activities.the continuous emergence of multi-drug-resistant bacteria drastically reduces the efficacy of antibiotic armory and, consequently, increases the frequency of therapeutic failure. the discovery of new antibacterial drugs is an urgent need. the present study reports the antibacterial and antioxidant activities of the methanol extract, fractions and iridoids from canthium subcordatum, a plant traditionally used as antidiabetic, anti-inflammatory, and antimicrobial.201728056944
[guillain-barré syndrome complicating shigella flexneri infection]. 201728024833
host cell nuclear localization of shigella flexneri effector ospf is facilitated by sumoylation.when shigella infect host cells, various effecter molecules are delivered into the cytoplasm of the host cell through the type iii secretion system (ttss) to facilitate their invasion process and control the host immune responses. among these effectors, the s. flexneri effector ospf dephosphorylates mitogen-activated protein kinases and translocates itself to the nucleus, thus preventing histone h3 modification to regulate expression of proinflammatory cytokines. despite the critical role of osp ...201727994213
functional and antigen-specific serum antibody levels as correlates of protection against shigellosis in a controlled human challenge study.shigella is an important cause of diarrheal disease in young children living in developing countries. no approved vaccines are available, and the development of vaccine candidates has been hindered by the lack of firm immunological correlates of protection, among other reasons. to address this gap in knowledge, we established quantitative assays to measure shigella-specific serum bactericidal antibody (sba) and opsonophagocytic killing antibody (opka) activities and investigated their potential ...201727927680
finding potential therapeutic targets against shigella flexneri through proteome exploration.background:shigella flexneri is a gram negative bacteria that causes the infectious disease "shigellosis." s. flexneri is responsible for developing diarrhea, fever, and stomach cramps in human. antibiotics are mostly given to patients infected with shigella. resistance to antibiotics can hinder its treatment significantly. upon identification of essential therapeutic targets, vaccine and drug could be effective therapy for the treatment of shigellosis. methods: the study was designed for the id ...201627920755
anticancer and antibacterial secondary metabolites from the endophytic fungus penicillium sp. cam64 against multi-drug resistant gram-negative bacteria.the emergence of multiple-drug resistance bacteria has become a major threat and thus calls for an urgent need to search for new effective and safe anti-bacterial agents.201627917206
injections of predatory bacteria work alongside host immune cells to treat shigella infection in zebrafish larvae.bdellovibrio bacteriovorus are predatory bacteria that invade and kill a range of gram-negative bacterial pathogens in natural environments and in vitro [1, 2]. in this study, we investigated bdellovibrio as an injected, antibacterial treatment in vivo, using zebrafish (danio rerio) larvae infected with an antibiotic-resistant strain of the human pathogen shigella flexneri. when injected alone, bdellovibrio can persist for more than 24 hr in vivo yet exert no pathogenic effects on zebrafish larv ...201627889262
the shigella virulence factor icsa relieves n-wasp autoinhibition by displacing the verprolin homology/cofilin/acidic (vca) domain.shigella flexneri is a bacterial pathogen that invades cells of the gastrointestinal tract, causing severe dysentery. shigella mediates intracellular motility and spreading via actin comet tail formation. this process is dependent on the surface-exposed, membrane-embedded virulence factor icsa, which recruits the host actin regulator n-wasp. although it is clear that shigella requires n-wasp for this process, the molecular details of this interaction and the mechanism of n-wasp activation remain ...201727881679
shigella flexneri modulates stress granule composition and inhibits stress granule aggregation. 201627870195
the changing epidemiology of bacillary dysentery and characteristics of antimicrobial resistance of shigella isolated in china from 2004-2014.bacillary dysentery caused by bacteria of the genus shigella is a significant public health problem in developing countries such as china. the objective of this study was to analyze the epidemiological pattern of bacillary dysentery, the diversity of the causative agent, and the antimicrobial resistance patterns of shigella spp. for the purpose of determining the most effective allocation of resources and prioritization of interventions.201627863468
antibacterial and cytotoxic cytochalasins from the endophytic fungus phomopsis sp. harbored in garcinia kola (heckel) nut.the continuous emergence of multidrug-resistant (mdr) bacteria drastically reduced the efficacy of our antibiotic armory and consequently, increased the frequency of therapeutic failure. the search for bioactive constituents from endophytic fungi against mdr bacteria became a necessity for alternative and promising strategies, and for the development of novel therapeutic solutions. we report here the isolation and structure elucidation of antibacterial and cytotoxic compounds from phomopsis sp., ...201627842536
decreased susceptibility to azithromycin among clinical shigella isolates from china.the aim of this study was to detect the decreased susceptibility to azithromycin (dsa) and associated mechanisms in shigella from china. three hundred and ninety-two shigella isolates, including 134 shigella flexneri and 258 shigella sonnei isolates, were examined for minimum inhibitory concentrations (mics) and zone sizes to azithromycin by broth microdilution and disk diffusion methods, respectively. the mics were compared with corresponding zone diameters to find whether there was uniformity ...201627841958
intrinsic jnk-mapk pathway involvement requires daf-16-mediated immune response during shigella flexneri infection in c. elegans.the c-jun n-terminal kinase-mitogen-activated protein kinase (jnk-mapk) pathway assists in modulating signals for growth, survival, and metabolism, thereby coordinating many cellular events during normal and stress conditions. to understand the role of the jnk-mapk pathway during bacterial infection, an in vivo model organism caenorhabditis elegans was used. in order to check the involvement of the jnk-mapk pathway, the survival rate of c. elegans wild type (wt), and jnk-mapk pathway mutant worm ...201627838822
of men not mice: bactericidal/permeability-increasing protein expressed in human macrophages acts as a phagocytic receptor and modulates entry and replication of gram-negative bacteria.macrophages as immune cells prevent the spreading of pathogens by means of active phagocytosis and killing. we report here the presence of an antimicrobial protein, bactericidal/permeability-increasing protein (bpi) in human macrophages, which actively participates in engulfment and killing of gram-negative pathogens. our studies revealed increased expression of bpi in human macrophages during bacterial infection and upon stimulation with various pathogen-associated molecular patterns, viz., lps ...201627822215
deletion of toxin-antitoxin systems in the evolution of shigella sonnei as a host-adapted pathogen.pathogenic shigella spp. are the leading cause of bacterial dysentery, with shigella flexneri and shigella sonnei accounting for around 90% of cases worldwide. although s. flexneri causes most disease in low-income countries (following ingestion of contaminated food and/or water), s. sonnei predominates in wealthy countries and is mainly spread from person to person. although both species contain a large virulence plasmid, pinv, that is essential for the organism to cause disease, little is know ...201627819667
social buffering and contact transmission: network connections have beneficial and detrimental effects on shigella infection risk among captive rhesus macaques.in social animals, group living may impact the risk of infectious disease acquisition in two ways. on the one hand, social connectedness puts individuals at greater risk or susceptibility for acquiring enteric pathogens via contact-mediated transmission. yet conversely, in strongly bonded societies like humans and some nonhuman primates, having close connections and strong social ties of support can also socially buffer individuals against susceptibility or transmissibility of infectious agents. ...201627812426
the synthesis of ospd3 (shet2) in shigella flexneri is independent of ospc1.shigella flexneri is a gram-negative pathogen that invades the colonic epithelium and causes millions of cases of watery diarrhea or bacillary dysentery predominately in children under the age of 5 years in developing countries. the effector shigella enterotoxin 2 (shet2), or ospd3, is encoded by the sen or ospd3 gene on the virulence plasmid. previous literature has suggested that ospd3 is in an operon downstream of the ospc1 gene, and expression of both genes is controlled by a promoter upstre ...201627657187
diverted recycling-shigella subversion of rabs.small gtpases of the rab protein family control intracellular vesicular trafficking to allow their communication and maintenance. it is a common strategy for intracellular bacteria to exploit these pathways to shape their respective niches for survival. the subversion of rabs for the generation of an intracellular environment favoring the pathogen has been described almost exclusively for intracellular bacteria that reside within bacterial containing vacuoles (bcvs). however, less is known about ...201627763815
nmr assignments for the insertion domain of bacteriophage sf6 coat protein.the p22 bacteriophage group is a subgroup of the λ phage supercluster, comprised of the three major sequence types sf6, p22, and cus-3, based on their capsid proteins. our goal is to investigate the extent to which structure-function relationships are conserved for the viral coat proteins and i-domains in this subgroup. sf6 is a phage that infects the human pathogen shigella flexneri. the coat protein of sf6 assembles into a procapsid, which further undergoes maturation during dna packaging into ...201727798771
shigella vaccine development: finding the path of least resistance.shigella spp. represent the second most common etiologic pathogen causing childhood diarrhea in developing countries. there are no licensed shigella vaccines, and progress for such vaccines has been limited. in this issue of clinical and vaccine immunology, riddle and colleagues (m. s. riddle, r. w. kaminski, c. di paolo, c. k. porter, r. l. gutierrez, et al., clin vaccine immunol 23:908-917, 2016, http://dx.doi.org/10.1128/cvi.00224-16) report results from a phase i study of a parenterally admi ...201627707764
evaluation of antimicrobial resistance among salmonella and shigella isolates in the university hospital "st. george," plovdiv, bulgaria.the aim of this work is to study the epidemiology and antimicrobial resistance to the most commonly used antibiotics for the treatment of acute gastroenteritis caused by salmonella and shigella at the largest bulgarian hospital-university hospital "st. george," plovdiv-for the period 2009-2013. two hundred ninety strains were in vitro tested for resistance to 15 antimicrobial agents. the presence of extended-spectrum beta-lactamases (esbls) was demonstrated by a variety of specialized tests. for ...201727761725
the architecture of the cytoplasmic region of type iii secretion systems.type iii secretion systems (t3sss) are essential devices in the virulence of many gram-negative bacterial pathogens. they mediate injection of protein effectors of virulence from bacteria into eukaryotic host cells to manipulate them during infection. t3sss involved in virulence (vt3sss) are evolutionarily related to bacterial flagellar protein export apparatuses (ft3sss), which are essential for flagellar assembly and cell motility. the structure of the external and transmembrane parts of both ...201627686865
proteomic analysis of shigella virulence effectors secreted under different conditions.there are a series of novel effector molecules secreted by the type three secretion system (t3ss) of shigella spp. reported in recent years. in this study, a proteomic approach is applied to study t3ss effectors systematically. first, proteins secreted by the s. flexneri wild-type strain after congo red (cr) induction are separated and identified using two-dimensional electrophoresis (2-de) to display the relative abundance of all kinds of early effectors for the first time. then, a gene deletio ...201627666981
shigellosis murine model established by intraperitoneal and intranasal route of administration: a comparative comprehension overview.shigellosis, a major cause of mortality and morbidity, requires development of effective intervention strategy for which animal model mimicking human pathology is essential. among various animal models for shigellosis, mice being more convenient have been used wherein intraperitoneal and intranasal routes are preferred. with the aim to comprehend the comparative pathophysiological indicators, we have examined relatively high and low dose of shigella flexneri administered through intraperitoneal ...201727664045
mitochondria promote septin assembly into cages that entrap shigella for autophagy.septins are cytoskeletal proteins implicated in cytokinesis and host-pathogen interactions. during macroautophagy/autophagy of shigella flexneri, septins assemble into cage-like structures to entrap actin-polymerizing bacteria and restrict their dissemination. how septins assemble to entrap bacteria is not fully known. we discovered that mitochondria support septin cage assembly to promote autophagy of shigella. consistent with roles for the cytoskeleton in mitochondrial dynamics, we showed that ...201627629779
novel mutations in quinolone resistance-determining regions of gyra, gyrb, parc and pare in shigella flexneri clinical isolates from eastern chinese populations between 2001 and 2011.the aim of this study was to evaluate the prevalence of fluoroquinolone resistance and mechanisms of selected fluoroquinolone resistance in shigella flexneri isolates. a total of 624 s. flexneri strains isolated between 2001 and 2011 in jiangsu province of china were analysed for their fluoroquinolone susceptibility. the quinolone resistance-determining region of gyra, gyrb, parc and pare were amplified and sequenced. in general, 90.5 % of s. flexneri exhibited resistance to nalidixic acid. the ...201627620866
shigella flexneri suppresses nf-κb activation by inhibiting linear ubiquitin chain ligation.the linear ubiquitin chain assembly complex (lubac) is a multimeric e3 ligase that catalyses m1 or linear ubiquitination of activated immune receptor signalling complexes (rscs). mutations that disrupt linear ubiquitin assembly lead to complex disease pathologies including immunodeficiency and autoinflammation in both humans and mice, but microbial toxins that target lubac function have not yet been discovered. here, we report the identification of two homologous shigella flexneri type iii secre ...201627572974
extended spectrum β-lactamase producing shigella flexneri serotype-2 causing bacteremia in a patient with uncontrolled diabetes mellitus.we report a case of shigella flexneri serotype-2 causing bacteremia in an elderly gentleman with uncontrolled diabetes mellitus, who had no other apparent risk factors. antibiotic susceptibility testing revealed that the organism was a multidrug resistant extended spectrum beta-lactamase producing straian, which was confirmed by molecular characterization. this rare case alerts both the clinician and microbiologist to a previously unaddressed risk factor of shigella spp. causing bacteremia, as w ...201727510696
identification of novel bacterial dna gyrase inhibitors: an in silico study.owing to essential role in bacterial survival, dna gyrase has been exploited as a validated drug target. however, rapidly emerging resistance to gyrase-targeted drugs such as widely utilized fluoroquinolones reveals the necessity to develop novel compounds with new mechanism of actions against this enzyme. here, an attempt has been made to identify new drug-like molecules for shigella flexneri dna gyrase inhibition through in silico approaches. the structural similarity search was carried out us ...201727499795
evolved populations of shigella flexneri phage sf6 acquire large deletions, altered genomic architecture, and faster life cycles.genomic architecture is the framework within which genes and regulatory elements evolve and where specific constructs may constrain or potentiate particular adaptations. one such construct is evident in phages that use a headful packaging strategy that results in progeny phage heads packaged with dna until full rather than encapsidating a simple unit-length genome. here, we investigate the evolution of the headful packaging phage sf6 in response to barriers that impede efficient phage adsorption ...201627497318
molecular diagnosis and anti-microbial resistance patterns among shigella spp. isolated from patients with diarrhea.this study aims to determine the serogroup distribution and molecular diagnosis, as well as antimicrobial resistance profiles among shigella spp. isolated from patients with diarrhea in kerman, southeast of iran.201627458513
complex secondary metabolites from ludwigia leptocarpa with potent antibacterial and antioxidant activities.diarrhea continues to be one of the most common causes of morbidity and mortality among infants and children in developing countries. the aim of the present study was to evaluate the antibacterial and antioxidant activities of extracts and compounds from ludwigia leptocarpa, a plant traditionally used for its vermifugal, anti-dysenteric, and antimicrobial properties. a methanol extract was prepared by maceration of the dried plant and this was successively extracted with ethyl acetate to obtain ...201727431270
anoxia and glucose supplementation preserve neutrophil viability and function.functional studies of human neutrophils and their transfusion for clinical purposes have been hampered by their short life span after isolation. here, we demonstrate that neutrophil viability is maintained for 20 hours in culture media at 37°c under anoxic conditions with 3 mm glucose and 32 μg/ml dimethyloxalylglycine supplementation, as evidenced by stabilization of mcl-1, proliferating cell nuclear antigen (pcna), and pro-caspase-3. notably, neutrophil morphology (nucleus shape and cell-surfa ...201627402974
efficient iterative synthesis of o-acetylated tri- to pentadecasaccharides related to the lipopolysaccharide of shigella flexneri type 3 a through di- and trisaccharide glycosyl donors.protection against bacterial infections, including shigellosis, can be achieved by antibodies against the bacterial surface polysaccharide. in line with our efforts to develop vaccine candidates for shigellosis, we report herein the synthesis of penta-, deca-, and pentadecasaccharides as well as tri-, octa-, and tridecasaccharides as the endchain and intrachain fragments, respectively, of the surface polysaccharide of shigella flexneri 3 a, a prevalent serotype. the syntheses relied on the effic ...201727385615
unprecedented abundance of protein tyrosine phosphorylation modulates shigella flexneri virulence.evidence is accumulating that protein tyrosine phosphorylation plays a crucial role in the ability of important human bacterial pathogens to cause disease. while most works have concentrated on its role in the regulation of a major bacterial virulence factor, the polysaccharide capsule, recent studies have suggested a much broader role for this post-translational modification. this prompted us to investigate protein tyrosine phosphorylation in the human pathogen shigella flexneri. we first compl ...201627380737
detailed investigation of the immunodominant role of o-antigen stoichiometric o-acetylation as revealed by chemical synthesis, immunochemistry, solution conformation and std-nmr spectroscopy for shigella flexneri 3a.shigella flexneri 3a causes bacillary dysentery. its o-antigen has the {2)-[α-d-glcp-(1→3)]-α-l-rhap-(1→2)-α-l-rhap-(1→3)-[ac→2]-α-l-rhap-(1→3)-[ac→6]≈40 % -β-d-glcpnac-(1→} ([(e)abac cac d]) repeating unit, and the non-o-acetylated equivalent defines s. flexneri x. propyl hepta-, octa-, and decasaccharides sharing the (e')a'bac cd(e)a sequence, and their non-o-acetylated analogues were synthesized from a fully protected bac cd(e)a allyl glycoside. the stepwise introduction of orthogonally prote ...201627376496
molecular characterization and analysis of high-level multidrug-resistance of shigella flexneri serotype 4s strains from china.to conduct the first comprehensive analysis of shigella flexneri serotype 4s, a novel serotype found in 2010, we identified 24 serotype 4s isolates from 1973 shigellosis cases in china (2002-2014). the isolates were characterized by single nucleotide polymorphism (snp) phylogenetic analysis, pulsed-field gel electrophoresis (pfge) and multilocus sequence typing (mlst) to determine their genetic relatedness, and analysed further for their antimicrobial susceptibilities and antimicrobial resistanc ...201627374009
carbbuilder: software for building molecular models of complex oligo- and polysaccharide structures.carbbuilder is a portable software tool for producing three-dimensional molecular models of carbohydrates from the simple text specification of a primary structure. carbbuilder can generate a wide variety of carbohydrate structures, ranging from monosaccharides to large, branched polysaccharides. version 2.0 of the software, described in this article, supports monosaccharides of both mammalian and bacterial origin and a range of substituents for derivatization of individual sugar residues. this ...201627317625
shigella flexneri modulates stress granule composition and inhibits stress granule aggregation.invasion and multiplication of the facultative, cytosolic, enteropathogen shigella flexneri within the colonic epithelial lining leads to an acute inflammatory response, fever and diarrhea. during the inflammatory process, infected cells are subjected to numerous stresses including heat, oxidative stress and genotoxic stress. the evolutionarily conserved pathway of cellular stress management is the formation of stress granules that store translationally inactive cellular mrnas and interfere with ...201627282465
monoclonal antibodies to shigella lipopolysaccharide are useful for vaccine production.there is a significant need for an effective multivalent shigella vaccine that targets the most prevalent serotypes. most shigella vaccines under development utilize serotype-specific lipopolysaccharides (lpss) as a major component based on protection and epidemiological data. as vaccine formulations advance from monovalent to multivalent, assays and reagents need to be developed to accurately and reproducibly quantitate the amount of lpss from multiple serotypes in the final product. to facilit ...201627280622
mitochondria mediate septin cage assembly to promote autophagy of shigella.septins, cytoskeletal proteins with well-characterised roles in cytokinesis, form cage-like structures around cytosolic shigella flexneri and promote their targeting to autophagosomes. however, the processes underlying septin cage assembly, and whether they influence s. flexneri proliferation, remain to be established. using single-cell analysis, we show that the septin cages inhibit s. flexneri proliferation. to study mechanisms of septin cage assembly, we used proteomics and found mitochondria ...201627259462
prevalence, resistance patterns, and characterization of integrons of shigella flexneri isolated from jiangsu province in china, 2001-2011.to provide the epidemiology, resistance pattern, and characterization of integrons in shigella flexneri isolated between 2001 and 2011 in jiangsu province.201627220330
macropinosomes are key players in early shigella invasion and vacuolar escape in epithelial cells.intracellular pathogens include all viruses, many bacteria and parasites capable of invading and surviving within host cells. key to survival is the subversion of host cell pathways by the pathogen for the purpose of propagation and evading the immune system. the intracellular bacterium shigella flexneri, the causative agent of bacillary dysentery, invades host cells in a vacuole that is subsequently ruptured to allow growth of the pathogen within the host cytoplasm. s. flexneri invasion has bee ...201627182929
resistant shigella strains in refugees, august-october 2015, greece.shigellosis is endemic in most developing countries and thus a known risk in refugees and internally displaced persons. in 2015, a massive influx of refugees into greece, due to the political crisis in the middle east, led to the development of appropriate conditions for outbreaks of communicable diseases as shigellosis. we present a cluster of 16 shigellosis cases in refugees, detected by the implementation of a syndromic notification system in one transit centre in athens, between 20 august an ...201627180973
mxia, mxic and ipad regulate substrate selection and secretion mode in the t3ss of shigella flexneri.type iii secretion systems (t3sss) are central virulence devices for many gram-negative bacterial pathogens of humans, animals & plants. upon physical contact with eukaryotic host cells, they translocate virulence-mediating proteins, known as effectors, into them during infection. t3sss are gated from the outside by host-cell contact and from the inside via two cytoplasmic negative regulators, mxic and ipad in shigella flexneri, which together control the effector secretion hierarchy. their abse ...201627171191
mice with streptozotocin-induced hyperglycemia are susceptible to invasive enteric bacterial infection.diabetes mellitus and diarrhea are becoming increasingly burdensome worldwide, particularly in developing countries such as india. diabetic patients are susceptible to infection with pathogenic bacteria, particularly those causing invasive enteric infections. in this study, we observed changes in the pathophysiological features of mice with streptozotocin-induced hyperglycemia. in our experiments, both hyperglycemic and control mice were infected with pathogenic enteric bacteria-non-typhoidal sa ...201727169940
characterization of a multicomponent live, attenuated shigella flexneri vaccine.shigella flexneri is a leading cause of diarrheal disease in children under five in developing countries. there is currently no licensed vaccine and broad spectrum protection requires coverage of multiple serotypes. the live attenuated vaccines cvd 1213 and cvd 1215 were derived from two prominent s. flexneri serotypes: s. flexneri 3a and s. flexneri 6. to provide broad-spectrum immunity, they could be combined with cvd 1208s, a s. flexneri 2a strain that demonstrated promising results in phase ...201627106253
an approach to identify and characterize a subunit candidate shigella vaccine antigen.shigellosis remains a serious issue throughout the developing countries, particularly in children under the age of 5. numerous strategies have been tested to develop vaccines targeting shigellosis; unfortunately despite several years of extensive research, no safe, effective, and inexpensive vaccine against shigellosis is available so far. here, we illustrate in detail an approach to identify and establish immunogenic outer membrane proteins from shigella flexneri 2a as subunit vaccine candidate ...201627076146
macrophage apoptosis triggered by ipad from shigella flexneri.shigellosis, a potentially severe bacillary dysentery, is an infectious gastrointestinal disease caused by shigella spp. shigella invades the human colonic epithelium and avoids clearance by promoting apoptosis of resident immune cells in the gut. this process is dependent on the shigella type iii secretion system (t3ss), which injects effector proteins into target cells to alter their normal cellular functions. invasion plasmid antigen d (ipad) is a structural component that forms a complex at ...201627068089
crystal structure of the substrate-recognition domain of the shigella e3 ligase ipah9.8.infectious diseases caused by bacteria have significant impacts on global public health. during infection, pathogenic bacteria deliver a variety of virulence factors, called effectors, into host cells. the shigella effector ipah9.8 functions as an ubiquitin ligase, ubiquitinating the nf-κb essential modulator (nemo)/ikk-γ to inhibit host inflammatory responses. ipah9.8 contains leucine-rich repeats (lrrs) involved in substrate recognition and an e3 ligase domain. to elucidate the structural basi ...201627050259
bacteriophage tailspikes and bacterial o-antigens as a model system to study weak-affinity protein-polysaccharide interactions.understanding interactions of bacterial surface polysaccharides with receptor protein scaffolds is important for the development of antibiotic therapies. the corresponding protein recognition domains frequently form low-affinity complexes with polysaccharides that are difficult to address with experimental techniques due to the conformational flexibility of the polysaccharide. in this work, we studied the tailspike protein (tsp) of the bacteriophage sf6. sf6tsp binds and hydrolyzes the high-rham ...201627045683
linear synthesis of the hexasaccharide related to the repeating unit of the o-antigen from shigella flexneri serotype 1d (i: 7,8).total synthesis of the hexasaccharide repeating unit of the o-antigen from shigella flexneri serotype 1d (i: 7,8), α-d-glcp-(1→3)-α-l-rhap-(1→2)-α-l-rhap-(1→3)-α-l-rhap-(1→3)-[α-d-glcp-(1→4)]-β-d-glcpnac, is reported by following a linear strategy. the target hexasaccharide was synthesized by sequential glycosylations of suitably protected monosaccharide derivatives prepared from commercially available monosaccharides through rational protecting group manipulations. stereoselective glycosylation ...201627043468
molecular and cellular mechanisms of shigella flexneri dissemination.the intracellular pathogen shigella flexneri is the causative agent of bacillary dysentery in humans. the disease is characterized by bacterial invasion of intestinal cells, dissemination within the colonic epithelium through direct spread from cell to cell, and massive inflammation of the intestinal mucosa. here, we review the mechanisms supporting s. flexneri dissemination. the dissemination process primarily relies on actin assembly at the bacterial pole, which propels the pathogen throughout ...201627014639
a novel small rna regulates tolerance and virulence in shigella flexneri by responding to acidic environmental changes.shigella flexneri is an important cause of bacillary dysentery in developing countries. small regulatory rnas (srnas) play essential roles in diverse cellular processes. we found a novel srna ssr1 based on rt-pcr, northern blot, and 5'race in s. flexneri. ssr1 responds to acidic environmental changes, as shown by a strong linear correlation between the ph value and ssr1 expression (r = 0.785, p < 0.05) using the qrt-pcr method. deletion of ssr1 results in growth retardation at ph values ranging ...201627014636
evaluation of molecular methods for serotyping shigella flexneri.shigella flexneri can be phenotypically serotyped using antisera raised to type-specific somatic antigens and group factor antigens and genotypically serotyped using pcr targeting o-antigen synthesis or modification genes. the aim of this study was to evaluate a real-time pcr for serotyping s. flexneri and to use whole-genome sequencing (wgs) to investigate the phenotypic and genotypic serotype identifications. of the 244 cultures tested retrospectively, 226 (92.6%) had concordant results betwee ...201626984974
spa47 is an oligomerization-activated type three secretion system (t3ss) atpase from shigella flexneri.gram-negative pathogens often use conserved type three secretion systems (t3ss) for virulence. the shigella type three secretion apparatus (t3sa) penetrates the host cell membrane and provides a unidirectional conduit for injection of effectors into host cells. the protein spa47 localizes to the base of the apparatus and is speculated to be an atpase that provides the energy for t3sa formation and secretion. here, we developed an expression and purification protocol, producing active spa47 and p ...201626947936
visualizing the translocation and localization of bacterial type iii effector proteins by using a genetically encoded reporter system.bacterial type iii secretion system (t3ss) effector proteins are critical determinants of infection for many animal and plant pathogens. however, monitoring of the translocation and delivery of these important virulence determinants has proved to be technically challenging. here, we used a genetically engineered lov (light-oxygen-voltage) sensing domain derivative to monitor the expression, translocation, and localization of bacterial t3ss effectors. we found the escherichia coli o157:h7 bacteri ...201626921426
a synthetic carbohydrate conjugate vaccine candidate against shigellosis: improved bioconjugation and impact of alum on immunogenicity.conjugation chemistry is among the most important parameters governing the efficacy of glycoconjugate vaccines. high robustness is required to ensure high yields and batch to batch reproducibility. herein, we have established a robust bioconjugation protocol based on the thiol-maleimide addition. major variables were determined and acceptable margins were investigated for a synthetic pentadecasaccharide-tetanus toxoid conjugate, which is a promising vaccine candidate against shigella flexneri se ...201626918643
prevalence and virulence genes of shigella spp. isolated from patients with diarrhea in rosario, argentina.the aim of this study was to determine the prevalence and virulence factors of shigella species isolated from patients with diarrhea. shigella species were isolated from 1,022 stool samples collected from different hospitals in rosario, argentina. the isolates were characterized using phenotypic tests, serotyping, and detection of virulence genes by pcr. one hundred strains (9.8% of samples collected) of shigella were isolated. shigella flexneri was the most frequently identified species (74%), ...201626902216
evaluation of the safety, tolerability, and immunogenicity of an oral, inactivated whole-cell shigella flexneri 2a vaccine in healthy adult subjects.shigella causes high morbidity and mortality worldwide, but there is no licensed vaccine for shigellosis yet. we evaluated the safety and immunogenicity of a formalin-inactivated whole-cell shigella flexneri2a vaccine, sf2awc, given orally to adult volunteers. in a double-blind, placebo-controlled trial, 82 subjects were randomized to receive three doses of vaccine in dose escalation (2.6 ± 0.8 × 10(8), × 10(9), × 10(10), and × 10(11)vaccine particles/ml). vaccine safety was actively monitored, ...201626865592
structural insights into the fluoroquinolone resistance mechanism of shigella flexneri dna gyrase and topoisomerase iv.traveler's diarrhea (td) is an important public health concern that can result from a variety of intestinal pathogens, including bacteria, parasites, and virus. a number of antibiotics are being used to cure td, but due to widespread use of these antibiotics, the pathogens are becoming resistant to them. in this work, we performed docking studies of dna gyrasea (gyra) and topoisomerase iv (parc) of shigella flexneri and their mutants with two different fluoroquinolones, ciprofloxacin and norflox ...201626859259
structural analysis of the active site architecture of the vapc toxin from shigella flexneri.the vapc toxin from the shigella flexneri 2a virulence plasmid pmysh6000 belongs to the pin domain protein family, which is characterized by a conserved fold with low amino acid sequence conservation. the toxin is a bona fide mg(2+) -dependent ribonuclease and has been shown to target initiator trna(fmet) in vivo. here, we present crystal structures of active site catalytic triad mutants d7a, d7n, and d98n of the vapc toxin in absence of antitoxin. in all structures, as well as in solution, vapc ...201626833558
pi5p triggers icam-1 degradation in shigella infected cells, thus dampening immune cell recruitment.shigella flexneri, the pathogen responsible for bacillary dysentery, has evolved multiple strategies to control the inflammatory response. here, we show that shigella subverts the subcellular trafficking of the intercellular adhesion molecule-1 (icam-1), a key molecule in immune cell recruitment, in a mechanism dependent on the injected bacterial enzyme ipgd and its product, the lipid mediator pi5p. overexpression of ipgd, but not a phosphatase dead mutant, induced the internalization and the de ...201626776508
[analysis of the drug resistance and the integron resistance gene cassette's characteristics of shigella flexneri].to investigate the correlation between shigella flexneri multi-drug resistance and drug resistance gene cassette of integrons.201526758113
flexibility at a glycosidic linkage revealed by molecular dynamics, stochastic modeling, and (13)c nmr spin relaxation: conformational preferences of α-l-rhap-α-(1 → 2)-α-l-rhap-ome in water and dimethyl sulfoxide solutions.the monosaccharide l-rhamnose is common in bacterial polysaccharides and the disaccharide α-l-rhap-α-(1 → 2)-α-l-rhap-ome represents a structural model for a part of shigella flexneri o-antigen polysaccharides. utilization of [1'-(13)c]-site-specific labeling in the anomeric position at the glycosidic linkage between the two sugar residues facilitated the determination of transglycosidic nmr (3)jch and (3)jcc coupling constants. based on these spin-spin couplings the major state and the conforma ...201626741055
shigella infections: a two year experience in cancer patients.to identify clinical and microbiological characteristics of shigella infections among cancer patients.201626712178
bacterial e3 ubiquitin ligase ipah4.5 of shigella flexneri targets tbk1 to dampen the host antibacterial response.ifn regulatory factors play a pivotal role in many cellular processes, including inflammatory and immune responses. their activation is tightly regulated by tank-binding kinase 1 (tbk1). in response to microbial components, tbk1 activates ifn regulatory factor 3 (irf3) and cytokine expression. in this article, we show that tbk1 is a novel target of the ipah4.5 protein, a shigella type iii effector possessing e3 ubiquitin ligase activity. remarkably, ipah4.5 interacts with tbk1 and promotes its k ...201626700764
clinical implications of reduced susceptibility to fluoroquinolones in paediatric shigella sonnei and shigella flexneri infections.we aimed to quantify the impact of fluoroquinolone resistance on the clinical outcome of paediatric shigellosis patients treated with fluoroquinolones in southern vietnam. such information is important to inform therapeutic management for infections caused by this increasingly drug-resistant pathogen, responsible for high morbidity and mortality in young children globally.201626679253
Displaying items 10701 - 10800 of 11070