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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
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
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
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
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
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
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
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
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
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
a small-scale experiment of using phage-based probiotic dietary supplement for prevention of e. coli traveler's diarrhea.traveler's diarrhea (td) is caused by escherichia coli in 30% of cases. we have developed a phage cocktail for prophylaxis of td caused by e.coli, shigella flexneri, shigella sonnei, salmonella enterica, listeria monocytogenes or staphylococcus aureus, and investigated its effectiveness against infection caused by the non-pathogenic lac (-) strain of e.coli k12 c600 in animal and human trials. on the 6th day of both animal and human trials e. coli k12 c600 strain was detected in titer of 10(4) c ...201726458758
development of a high-throughput method to evaluate serum bactericidal activity using bacterial atp measurement as survival readout.serum bactericidal activity (sba) assay is the method of choice to evaluate the complement-mediated functional activity of both infection- and vaccine-induced antibodies. to perform a typical sba assay, serial dilutions of sera are incubated with target bacterial strains and complement. the conventional sba assay is based on plating on agar the sba reaction mix and counting the surviving bacterial colony forming units (cfu) at each serum dilution. even with automated colony counting, it is labor ...201728192483
antimicrobial use for and resistance of zoonotic bacteria recovered from nonhuman primates.as a growing threat to human and animal health, antimicrobial resistance (amr) has become a central public-health topic. largescale surveillance systems, such as the national antimicrobial resistance monitoring system (narms), are now established to monitor and provide guidance regarding amr, but comprehensive literature on amr among nhp is sparse. this study provides data regarding current antimicrobial use strategies and the prevalence of amr in zoonotic bacteria recovered from nhp within biom ...201728128070
relationship between drug resistance and the clustered, regularly interspaced, short, palindromic repeat-associated protein genes cas1 and cas2 in shigella from giant panda dung.to detect drug resistance in shigella obtained from the dung of the giant panda, explore the factors leading to drug resistance in shigella, understand the characteristics of clustered, regularly interspaced, short, palindromic repeats (crispr), and assess the relationship between crispr and drug resistance.201728207509
attachment of 13 types of foodborne bacteria to jalapeño and serrano peppers and antibacterial effect of roselle calyx extracts, sodium hypochlorite, colloidal silver, and acetic acid against these foodborne bacteria on peppers.chili peppers are a very important crop in mexico. however, these peppers have been associated with salmonella infection outbreaks in the united states, and salmonella and diarrheagenic escherichia coli pathotypes have been isolated from jalapeño and serrano peppers in mexico. to decrease microbial contamination of fruits and vegetables, chemical agents are commonly used; however, chemical agents used to eliminate pathogenic bacteria on vegetables have a limited antimicrobial effect. roselle ( h ...201728199144
bacterium-derived cell-penetrating peptides deliver gentamicin to kill intracellular pathogens.commonly used antimicrobials show poor cellular uptake and often have limited access to intracellular targets, resulting in low antimicrobial activity against intracellular pathogens. an efficient delivery system to transport these drugs to the intracellular site of action is needed. cell-penetrating peptides (cpps) mediate the internalization of biologically active molecules into the cytoplasm. here, we characterized two cpps, α1h and α2h, derived from the yersinia enterocolitica yopm effector ...201728096156
infection of human intestinal epithelial cells by invasive bacteria activates nf-κb and increases icam-1 expression through nod1.nucleotide-binding oligomerization domain 1 (nod1) is required for primary intestinal epithelial cells (iecs) to respond to natural mucopeptides secreted by gram-negative bacteria. infection of human iecs with invasive bacteria up-regulates intercellular adhesion molecule-1 (icam-1) expression. however, the role of nod family members in host defense has been largely unknown. the aim of this study was to determine whether there is a functional role for nod1 in the up-regulation of icam-1 expressi ...201728092699
recent outbreaks of shigellosis in california caused by two distinct populations of shigella sonnei with either increased virulence or fluoroquinolone resistance.shigella sonnei has caused unusually large outbreaks of shigellosis in california in 2014 and 2015. preliminary data indicated the involvement of two distinct bacterial populations, one from san diego and san joaquin (sdi/sjo) and one from the san francisco (sfr) bay area. whole-genome analysis and antibiotic susceptibility testing of 68 outbreak and archival isolates of s. sonnei were performed to investigate the microbiological factors related to these outbreaks. both sdi/sjo and sfr populatio ...201728028547
a single and two step isomerization process for d-tagatose and l-ribose bioproduction using l-arabinose isomerase and d-lyxose isomerase.l-ribose and d-tagatose are biochemically synthesized using sugar isomerases. the l-arabinose isomerase gene from shigella flexneri (sf-ai) was cloned and expressed in escherichia coli bl-21. sf-ai was applied for the bioproduction of d-tagatose from d-galactose. l-ribose synthesis was performed by two step isomerization using sf-ai and d-lyxose/ribose isomerase from cohnella laevoribosii. the overall 22.3% and 25% conversion rate were observed for d-tagatose and l-ribose production from d-galac ...201728010770
identification of escherichia coli and shigella species from whole-genome sequences.escherichia coli and shigella species are closely related and genetically constitute the same species. differentiating between these two pathogens and accurately identifying the four species of shigella are therefore challenging. the organism-specific bioinformatics whole-genome sequencing (wgs) typing pipelines at public health england are dependent on the initial identification of the bacterial species by use of a kmer-based approach. of the 1,982 escherichia coli and shigella sp. isolates ana ...201727974538
virulotyping of shigella spp. isolated from pediatric patients in tehran, iran.shigellosis is a considerable infectious disease with high morbidity and mortality among children worldwide. in this survey the prevalence of four important virulence genes including ial, ipah, set1a, and set1b were investigated among shigella strains and the related gene profiles identified in the present investigation, stool specimens were collected from children who were referred to two hospitals in tehran, iran. the samples were collected during 3 years (2008-2010) from children who were sus ...201728218003
characteristics of volatile organic compounds produced from five pathogenic bacteria by headspace-solid phase micro-extraction/gas chromatography-mass spectrometry.the characteristics of volatile compounds from five different bacterial species, escherichia coli o157:h7, salmonella enteritidis, shigella flexneri, staphylococcus aureus, and listeria monocytogenes, growing, respectively, in trypticase soy broth were monitored by headspace solid-phase micro-extraction/gas chromatography-mass spectrometry. the results showed that most volatile organic compounds (vocs) of five pathogens started to increase after the sixth to tenth hour. methyl ketones and long c ...201727874211
in vitro screening and in silico validation revealed key microbes for higher production of significant therapeutic enzyme l-asparaginase.l-asparaginase is an enzyme of medical prominence and reputable as a chemotherapeutic agent. it also has immense potential to cure autoimmune and infectious diseases. the vast application of this enzyme in healthcare sector increases its market demand. however, presently the huge market demand is not achieved completely. this serves the basis to explore better producer microbial strains to bridge the gap between huge demand and supply of this therapeutic enzyme. the present study deals with the ...201728110669
[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
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
alpk1 controls tifa/traf6-dependent innate immunity against heptose-1,7-bisphosphate of gram-negative bacteria.during infection by invasive bacteria, epithelial cells contribute to innate immunity via the local secretion of inflammatory cytokines. these are directly produced by infected cells or by uninfected bystanders via connexin-dependent cell-cell communication. however, the cellular pathways underlying this process remain largely unknown. here we perform a genome-wide rna interference screen and identify tifa and traf6 as central players of shigella flexneri and salmonella typhimurium-induced inter ...201728222186
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
flagellar expression in clinical isolates of non-typeable haemophilus influenzae.haemophilus influenzae is a commensal organism found in the upper respiratory tract of humans. when h. influenzae becomes a pathogen, these bacteria can move out of their commensal niche and cause multiple respiratory tract diseases such as otitis media, sinusitis, conjunctivitis and bronchitis in children, and chronic obstructive pulmonary disease in adults. however, h. influenzae is currently considered a non-flagellate bacterium.201728513418
antimicrobial activity of endophytic bacterial populations isolated from medical plants of iran.endophytic actinobacteria colonize inside the plant tissues without causing damages to the host plant. since these microorganisms colonize in the different parts of plants and can stop plant disease, they have been applied as biological agents for controlling human diseases. the aim of this study was molecular identification and measuring the antimicrobial activity of endophytic actinomycetes isolated from medicinal plants of iran.201728775818
cyclohexene-fused 1,3-oxazines with selective antibacterial and antiparasitic action and low cytotoxic effects.oxazine derivatives, a class of heterocyclic compounds, exhibit a variety of biological properties, such as anticonvulsant and antitumor activities. in this study, we evaluated the effect of two cyclohexene-fused 1,3-oxazines (cis‑1-benzyl-n-phenyl-1,4,4a,5,8,8a-hexahydro-3,1-benzoxazin-2-imine (1) and trans‑n-phenyl-1,4,4a,5,8,8a-hexahydro-3,1-benzoxazin-2-imine (2)) in cultures of bacillus cereus, enterococcus faecalis, escherichia coli, klebsiella pneumoniae, salmonella enterica, serratia mar ...201728755871
use of whey as a culture medium for bacillus clausii for the production of protein hydrolysates with antimicrobial and antioxidant activity.the use of whey as a natural culture medium to produce hydrolysates with antimicrobial from bacillus clausii is the objective of this research. the fermentation process was carried out at 25 ℃ for five days, where proteolytic activity, soluble peptides quantification, and antimicrobial activity using the disc diffusion method were determined every day. the fermented whey reached values ​​of proteolytic activity between 90 and 260 u ml(-1) and a production of soluble peptides between 100 and 2070 ...201728816527
colorimetric sensing of toxic metal and antibacterial studies by using bioextract synthesized silver nanoparticles.here, we report the simple and cost effective colorimetric technique for the determination of toxic metals (hg(2+)) in aqueous sample by using bioextract silver nanoparticles (agnps). the indigenous agnps were synthesised by green and ecologically friendly style using extract of fig (ficus carica) leaf. the synthesized agnps were confirmed by uv-vis spectroscopy, ft-ir spectroscopy, and scanning electron microscopy methods. the synthesis of agnps was observed by its colour changing from light ye ...201728748516
altered antibacterial activity of curcumin in the presence of serum albumin, plasma and whole blood.antibacterial effect is one of the major therapeutic activities of plant-derived curcumin. this work evaluated the effect of serum albumin, human plasma, and whole blood on the in vitro activity of curcumin against eight clinical bacterial isolates by standard broth microdilution and plate-counting methods. toxicological effects of curcumin towards human red blood cells (rbcs) and peripheral blood mononuclear cells (pbmcs) were also investigated. curcumin exhibited weak activity against gram-neg ...201728649069
antibacterial activity of crude extracts of some south african medicinal plants against multidrug resistant etiological agents of diarrhoea.this study evaluated the antibacterial activity of some plants used in folklore medicine to treat diarrhoea in the eastern cape province, south africa.201728629407
antimicrobial, anticancer, and antioxidant compounds from premna resinosa growing in saudi arabia.premna resinosa (hochst.) schauer (lamiaceae) is used in many places to treat bronchitis, respiratory illness and convulsions of the rib cage.201728508699
dna aptamer identification and characterization for e. coli o157 detection using cell based selex method.escherichia coli (e. coli) o157:h7 is a foodborne pathogen that causes symptoms in humans. its rapid identification should be considered to avoid toxic effects of the pathogen. in this study, systematic evolution of ligands by exponential enrichment using whole cells (cell-selex) method was used for recognizing e. coli strain, o157 by single-stranded dna library of aptamer. nine rounds of cell-selex procedure were applied using o157, as a whole-cell target, with o42, k12, top10, dh5α e. coli cel ...201728818557
an attenuated shigella mutant lacking the rna-binding protein hfq provides cross-protection against shigella strains of broad serotype.few live attenuated vaccines protect against multiple serotypes of bacterial pathogen because host serotype-specific immune responses are limited to the serotype present in the vaccine strain. here, immunization with a mutant of shigella flexneri 2a protected guinea pigs against subsequent infection by s. dysenteriae type 1 and s. sonnei strains. this deletion mutant lacked the rna-binding protein hfq leading to increased expression of the type iii secretion system via loss of regulation, result ...201728727722
role of the virulence plasmid in acid resistance of shigella flexneri.virulence plasmid (vp) acquisition was a key step in the evolution of shigella from a non-pathogenic escherichia coli ancestor to a pathogenic genus. in addition, the co-evolution and co-ordination of chromosomes and vps was also a very important step in the evolutionary process. to investigate the cross-talk between vps and bacterial chromosomes, we analyzed the expression profiles of protein complexes and protein monomers in three wild-type shigella flexneri strains and their corresponding vp ...201728440329
antibacterial effects of lactobacillus isolates of curd and human milk origin against food-borne and human pathogens.this study was undertaken to assess the antibacterial efficacy of lactobacilli isolated from curd and human milk samples. identities of thirty-one different lactobacilli (20 from curd and 11 from human milk) were confirmed by genus-specific pcr and 16s rrna-based sequencing. these strains belonged to five species, lactobacillus casei, l. delbrueckii, l. fermentum, l. plantarum, and l. pentosus. antibacterial activities of cell-free supernatants (cfss) of all the lactobacillus isolates were estim ...201728401466
antiprotozoal, antibacterial and antidiarrheal properties from the flowers of chiranthodendron pentadactylon and isolated flavonoids.chiranthodendron pentadactylon larreat. (sterculiaceae) is a mexican plant used in traditional medicine for the treatment of heart disease symptoms and infectious diarrhea.201728539715
bipc, a predicted burkholderia pseudomallei type 3 secretion system translocator protein with actin binding activity.burkholderia pseudomallei is an intracellular bacterial pathogen and the causative agent of melioidosis, a severe disease of humans and animals. like other clinically important gram-negative bacteria, fundamental to b. pseudomallei pathogenesis is the bsa type iii secretion system. the bsa system injects bacterial effector proteins into the cytoplasm of target host cells subverting cellular pathways for the benefit of the bacteria. it is required for invasion of non-phagocytic host cells, escape ...201728770177
type iii secretion in the melioidosis pathogen burkholderia pseudomallei.burkholderia pseudomallei is a gram-negative intracellular pathogen and the causative agent of melioidosis, a severe disease of both humans and animals. melioidosis is an emerging disease which is predicted to be vastly under-reported. type iii secretion systems (t3sss) are critical virulence factors in gram negative pathogens of plants and animals. the genome of b. pseudomallei encodes three t3sss. t3ss-1 and -2, of which little is known, are homologous to hrp2 secretion systems of the plant pa ...201728664152
antimicrobial natural product research: a review from a south african perspective for the years 2009-2016.this review provides information on the antimicrobial research which has taken place on south african natural products for the last eight years (2009-2016). this important field is the backbone of all studies involving the use of medicinal plants against infectious diseases and hence can form the mainstay for future studies.201728694104
stand-alone eal domain proteins form a distinct subclass of eal proteins involved in regulation of cell motility and biofilm formation in enterobacteria.the second messenger cyclic dimeric gmp (c-di-gmp) is almost ubiquitous among bacteria as are the c-di-gmp turnover proteins, which mediate the transition between motility and sessility. eal domain proteins have been characterized as c-di-gmp-specific phosphodiesterases. while most eal domain proteins contain additional, usually n-terminal, domains, there is a distinct family of proteins with stand-alone eal domains, exemplified by salmonella enterica serovar typhimurium proteins stm3611 (yhjh/p ...201728652301
listeria monocytogenes and shigella flexneri activate the nlrp1b inflammasome.activation of the innate immune receptor nlrp1b leads to the formation of an inflammasome, which induces autoproteolytic processing of pro-caspase-1, and ultimately to the release of inflammatory cytokines and to the execution of pyroptosis. one of the signals to which nlrp1b responds is metabolic stress that occurs in cells deprived of glucose or treated with metabolic inhibitors. nlrp1b might, therefore, sense microbial infection as intracellular pathogens such as listeria monocytogenes and sh ...201728808162
development of biopolymer composite films using a microfluidization technique for carboxymethylcellulose and apple skin particles.biopolymer films based on apple skin powder (asp) and carboxymethylcellulose (cmc) were developed with the addition of apple skin extract (ase) and tartaric acid (ta). asp/cmc composite films were prepared by mixing cmc with asp solution using a microfluidization technique to reduce particle size. then, various concentrations of ase and ta were incorporated into the film solution as an antioxidant and an antimicrobial agent, respectively. fourier transform infrared (ftir), optical, mechanical, w ...201728617325
comparative genomic and phylogenetic analysis of a shiga toxin producing shigella sonnei (stss) strain.shigella strains are important agents of bacillary dysentery, and in recent years shigella sonnei has emerged as the leading cause of shigellosis in industrialized and rapidly developing countries. more recently, several s. sonnei and shigella flexneri strains producing shiga toxin (stx) have been reported from sporadic cases and from an outbreak in america. in the present study we aimed to shed light on the evolution of a recently identified shiga toxin producing s. sonnei (stss) isolated in eu ...201728611956
evaluation of microplate immunocapture method for detection of vibrio cholerae, salmonella typhi and shigella flexneri from food.improved methods with better separation and concentration ability for detection of foodborne pathogens are in constant need. the aim of this study was to evaluate microplate immunocapture (ic) method for detection of salmonella typhi, shigella flexneri and vibrio cholerae from food samples to provide a better alternative to conventional culture based methods.201728851288
lubac-synthesized linear ubiquitin chains restrict cytosol-invading bacteria by activating autophagy and nf-κb.cell-autonomous immunity relies on the ubiquitin coat surrounding cytosol-invading bacteria functioning as an 'eat-me' signal for xenophagy. the origin, composition and precise mode of action of the ubiquitin coat remain incompletely understood. here, by studying salmonella typhimurium, we show that the e3 ligase lubac generates linear (m1-linked) polyubiquitin patches in the ubiquitin coat, which serve as antibacterial and pro-inflammatory signalling platforms. lubac is recruited via its subuni ...201728481331
genomic analysis and resistance mechanisms in shigella flexneri 2a strain 301.shigella flexneri is one of the most prominent pathogenic bacteria in developing countries. in the battle against shigellosis and other bacterial diseases, antibiotic resistance has become an increasing global public health threat. although the serious phenomenon of multidrug resistance (mdr) has been identified as one of the top three burdens on human health, resistance mechanisms are still poorly understood at the molecular level. in this study, we analyzed genomic data and the evolution of re ...201728853989
cardiolipin synthesis and outer membrane localization are required for shigella flexneri virulence.cardiolipin, an anionic phospholipid that resides at the poles of the inner and outer membranes, is synthesized primarily by the putative cardiolipin synthase clsa in shigella flexneri an s. flexneri clsa mutant had no cardiolipin detected within its membrane, grew normally in vitro, and invaded cultured epithelial cells, but it failed to form plaques in epithelial cell monolayers, indicating that cardiolipin is required for virulence. the clsa mutant was initially motile within the host cell cy ...201728851846
single-domain antibodies pinpoint potential targets within shigella invasion plasmid antigen d of the needle tip complex for inhibition of type iii secretion.numerous gram-negative pathogens infect eukaryotes and use the type iii secretion system (t3ss) to deliver effector proteins into host cells. one important t3ss feature is an extracellular needle with an associated tip complex responsible for assembly of a pore-forming translocon in the host cell membrane. shigella spp. cause shigellosis, also called bacillary dysentery, and invade colonic epithelial cells via the t3ss. the tip complex of shigella flexneri contains invasion plasmid antigen d (ip ...201728842484
vaccination with shigella flexneri 2a conjugate induces type 2a and cross-reactive type 6 antibodies in humans but not in mice.shigella flexneri (s. flexneri) 6 has emerged as an important cause of shigellosis. our efficacy study of shigella sonnei and s. flexneri 2a o-specific polysaccharide (o-sp) conjugates in 1-4year-olds had too few s. flexneri 2a cases for efficacy evaluation but surprisingly showed protection of 3-4year-olds, s. flexneri 2a-recipients, from s. flexneri 6 infection. to investigate this cross-protection antibodies to both shigella types were investigated in all sera remaining from previous studies. ...201728797729
trappc13 modulates autophagy and the response to golgi stress.tether complexes play important roles in endocytic and exocytic trafficking of lipids and proteins. in yeast, the multisubunit transport protein particle (trapp) tether regulates endoplasmic reticulum (er)-to-golgi and intra-golgi transport and is also implicated in autophagy. in addition, the trapp complex acts as a guanine nucleotide exchange factor (gef) for ypt1, which is homologous to human rab1a and rab1b. here, we show that human trappc13 and other trapp subunits are critically involved i ...201728536105
genome-wide identification of potential drug target in enterobacteriaceae family: a homology-based method.the enterobacteriaceae is a large family of gram-negative, facultative anaerobic, non-spore forming rod-shaped bacteria that includes harmless and pathogenic organisms. the emergence and development of drug resistance in enterobacteriaceae is complicating the treatment of serious infections. the aim of this study is to predict and characterize putative drug targets in enterobacteriaceae family employing a homology-based computational method. the final putative drug targets were qualitatively cha ...201728520499
innate recognition of intracellular bacterial growth is driven by the tifa-dependent cytosolic surveillance pathway.intestinal epithelial cells (iecs) act as sentinels for incoming pathogens. cytosol-invasive bacteria, such as shigella flexneri, trigger a robust pro-inflammatory nuclear factor κb (nf-κb) response from iecs that is believed to depend entirely on the peptidoglycan sensor nod1. we found that, during shigella infection, the traf-interacting forkhead-associated protein a (tifa)-dependent cytosolic surveillance pathway, which senses the bacterial metabolite heptose-1,7-bisphosphate (hbp), functions ...201728514661
genome sequence of shigella flexneri strain sp1, a diarrheal isolate that encodes an extended-spectrum β-lactamase (esbl).shigellosis is the most common cause of gastrointestinal infections in developing countries. in china, the species most frequently responsible for shigellosis is shigella flexneri. s. flexneri remains largely unexplored from a genomic standpoint and is still described using a vocabulary based on biochemical and serological properties. moreover, increasing numbers of esbl-producing shigella strains have been isolated from clinical samples. despite this, only a few cases of esbl-producing shigella ...201728499446
nasal delivery of protollin-adjuvanted h5n1 vaccine induces enhanced systemic as well as mucosal immunity in mice.sporadic, yet frequent human infections with avian h5n1 influenza a viruses continue to pose a potential pandemic threat. poor immunogenicity of unadjuvanted h5n1 vaccines warrants developing novel adjuvants and formulations as well as alternate delivery systems to improve their immunogenicity and efficacy. here, we show that protollin, a nasal adjuvant composed of neisseria meningitides outer membrane proteins non-covalently linked to shigella flexneri 2a lipopolysaccharide, is a potent nasal a ...201728499553
inhibition of shigella sonnei and shigella flexneri in hummus using citric acid and garlic extract.hummus (chickpea dip) is a ready-to-eat product that may pose a significant risk to human if pathogens are present. several organisms including shigella spp. have been isolated from hummus. however, studies on the survival and inhibition of shigella spp. in food are scarce. this study investigated the growth pattern of sh. sonnei and sh. flexneri in hummus at different temperatures (4, 10, and 24 °c). additionally, the inhibitory activity of different concentrations of citric acid (ca) (0.5%, 1. ...201728732128
effective protection of mice against shigella flexneri with a new self-adjuvant multicomponent vaccine.the aim of this study was to develop an immunogenic protective product against shigella flexneri by employing a simple and safe heat treatment-based strategy.201728721849
septins restrict inflammation and protect zebrafish larvae from shigella infection.shigella flexneri, a gram-negative enteroinvasive pathogen, causes inflammatory destruction of the human intestinal epithelium. infection by s. flexneri has been well-studied in vitro and is a paradigm for bacterial interactions with the host immune system. recent work has revealed that components of the cytoskeleton have important functions in innate immunity and inflammation control. septins, highly conserved cytoskeletal proteins, have emerged as key players in innate immunity to bacterial in ...201728650995
characterization of extended-spectrum β-lactamase genes of shigella flexneri isolates with fosfomycin resistance from patients in china.the emergence of fosfomycin resistance and extended-spectrum β-lactamase (esbl) genes is a serious threat to public health and a new challenge in shigellosis treatment. the purpose of this study was to identify fosfomycin resistance and characterize β-lactamase genes in fos-carrying isolates of shigella flexneri from patients in china.201728643490
siga-shigella immune complexes interact with dectin-1 and signr3 to differentially regulate mouse peyer's patch and mesenteric lymph node dendritic cell's responsiveness.in addition to contributing to immune exclusion at mucosal surfaces, secretory iga (siga) made of polymeric iga and secretory component is able to selectively reenter via microfold cells into peyer's patches (pps) present along the intestine and to associate with dendritic cells (dcs) of the cd11c(+)cd11b(+)mhcii(+)f4/80(-)cd8(-)phenotype in the subepithelial dome region and the draining mesenteric lymph nodes (mlns). however, the nature of the receptor(s) for siga on murine pp and mln dcs is un ...201728587925
in vitro resistance selection in shigella flexneri by azithromycin, ceftriaxone, ciprofloxacin, levofloxacin, and moxifloxacin.shigella flexneri continues to be a major cause of diarrhea-associated illness, and increasing resistance to first-line antimicrobials complicates the treatment of infections caused by this pathogen. we investigated the pharmacodynamics of current antimicrobial treatments for shigellosis to determine the likelihood of resistance promotion with continued global antimicrobial use. the mutant prevention concentration (mpc) and mutant selection window (msw) were determined for azithromycin, ceftriax ...201728483960
virf relieves the transcriptional attenuation of the virulence gene icsa of shigella flexneri affecting the icsa mrna-rnag complex formation.virf is the master activator of virulence genes of shigella and its expression is required for the invasion of the human intestinal mucosa by pathogenic bacteria. virf was shown to directly activate the transcription of virb and icsa, which encode two essential proteins involved in the pathogenicity process, by binding their promoter regions. in this study, we demonstrate by band shift, enzymatic probing and cross-linking experiments that virf, in addition to dna, can also bind the icsa transcri ...201728458662
genome sequencing analysis of atypical shigella flexneri isolated in korea.an atypical shigella flexneri strain with a plural agglutination pattern [i.e., reacting not only with serum samples containing type antigen ii but also with serum samples containing group antigens (3)4 and 7(8)] was selected for genome sequencing, with the aim of obtaining additional comparative information about such strains.201728443228
analysis of host microrna function uncovers a role for mir-29b-2-5p in shigella capture by filopodia.micrornas play an important role in the interplay between bacterial pathogens and host cells, participating as host defense mechanisms, as well as exploited by bacteria to subvert host cellular functions. here, we show that micrornas modulate infection by shigella flexneri, a major causative agent of bacillary dysentery in humans. specifically, we characterize the dual regulatory role of mir-29b-2-5p during infection, showing that this microrna strongly favors shigella infection by promoting bot ...201728394930
cnbp acts as a key transcriptional regulator of sustained expression of interleukin-6.the transcription of inflammatory genes is an essential step in host defense activation. here, we show that cellular nucleic acid-binding protein (cnbp) acts as a transcription regulator that is required for activating the innate immune response. we identified specific cnbp-binding motifs present in the promoter region of sustained inflammatory cytokines, thus, directly inducing the expression of target genes. in particular, lipopolysaccharide (lps) induced cnbp expression through an nf-κb-depen ...201728168305
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