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development of a novel genus-specific real-time pcr assay for detection and differentiation of bartonella species and genotypes.the genus bartonella includes numerous species with varied host associations, including several that infect humans. development of a molecular diagnostic method capable of detecting the diverse repertoire of bartonella species while maintaining genus specificity has been a challenge. we developed a novel real-time pcr assay targeting a 301-bp region of the ssra gene of bartonella and demonstrated specific amplification in over 30 bartonella species, subspecies, and strains. subsequent analysis o ...201222378904
molecular evidence for the thriving of campylobacter jejuni st-4526 in japan.campylobacter jejuni is a leading cause of human gastroenteritis worldwide. this study aimed at a better understanding of the genetic diversity of this pathogen disseminated in japan. we performed multilocus sequence typing (mlst) of campylobacter jejuni isolated from different sources (100 human, 61 poultry, and 51 cattle isolates) in japan between 2005 and 2006. this approach identified 62 sequence types (sts) and 19 clonal complexes (ccs), including 11 novel sts. these 62 sts were phylogeneti ...201223144873
the yfe and feo transporters are involved in microaerobic growth and virulence of yersinia pestis in bubonic plague.the yfe/sit and feo transport systems are important for the growth of a variety of bacteria. in yersinia pestis, single mutations in either yfe or feo result in reduced growth under static (limited aeration), iron-chelated conditions, while a yfe feo double mutant has a more severe growth defect. these growth defects were not observed when bacteria were grown under aerobic conditions or in strains capable of producing the siderophore yersiniabactin (ybt) and the putative ferrous transporter fetm ...201222927049
crystal structure of the campylobacter jejuni cj0090 protein reveals a novel variant of the immunoglobulin fold among bacterial lipoproteins.bacterial lipoproteins play an important role in bacterial pathogenesis and physiology. the genome of campylobacter jejuni, a major foodborn pathogen, is predicted to contain over 20 lipoproteins. however, the functions of the majority of c. jejuni lipoproteins remain unknown. the cj0090 protein is encoded by a lipoprotein operon composed of cj0089, cj0090, and cj0091. here, we report the crystal structure of cj0090 at 1.9 å resolution, revealing a novel variant of the immunoglobulin fold with β ...201222987763
a small multidrug resistance-like transporter involved in the arabinosylation of arabinogalactan and lipoarabinomannan in mycobacteria.the biosynthesis of the major cell envelope glycoconjugates of mycobacterium tuberculosis is topologically split across the plasma membrane, yet nothing is known of the transporters required for the translocation of lipid-linked sugar donors and oligosaccharide intermediates from the cytoplasmic to the periplasmic side of the membrane in mycobacteria. one of the mechanisms used by prokaryotes to translocate lipid-linked phosphate sugars across the plasma membrane relies on translocases that shar ...201223038254
iron and ph-responsive ftrabcd ferrous iron utilization system of bordetella species.a putative operon encoding an uncharacterized ferrous iron transport (ftrabcd) system was previously identified in cdna microarray studies. in growth studies using buffered medium at ph values ranging from ph 6.0 to 7.6, bordetella pertussis and bordetella bronchiseptica ftrabcd system mutants showed dramatic reductions in growth yields under iron-restricted conditions at ph 6.0, but had no growth defects at ph 7.6. supplementation of culture medium with 2 mm ascorbate reductant was inhibitory t ...201222924881
beyond growth: novel functions for bacterial cell wall hydrolases.the peptidoglycan cell wall maintains turgor pressure and cell shape of most bacteria. cell wall hydrolases are essential, together with synthases, for growth and daughter cell separation. recent work in diverse organisms has uncovered new cell wall hydrolases that act autonomously or on neighboring cells to modulate invasion of prey cells, cell shape, innate immune detection, intercellular communication, and competitor lysis. the hydrolases involved in these processes catalyze the cleavage of b ...201222944244
a bioinformatic strategy for the detection, classification and analysis of bacterial autotransporters.autotransporters are secreted proteins that are assembled into the outer membrane of bacterial cells. the passenger domains of autotransporters are crucial for bacterial pathogenesis, with some remaining attached to the bacterial surface while others are released by proteolysis. an enigma remains as to whether autotransporters should be considered a class of secretion system, or simply a class of substrate with peculiar requirements for their secretion. we sought to establish a sensitive search ...201222905239
identification of a general o-linked protein glycosylation system in acinetobacter baumannii and its role in virulence and biofilm formation.acinetobacter baumannii is an emerging cause of nosocomial infections. the isolation of strains resistant to multiple antibiotics is increasing at alarming rates. although a. baumannii is considered as one of the more threatening "superbugs" for our healthcare system, little is known about the factors contributing to its pathogenesis. in this work we show that a. baumannii atcc 17978 possesses an o-glycosylation system responsible for the glycosylation of multiple proteins. 2d-dige and mass spec ...201222685409
lipopolysaccharides: from erinyes to charites.following the discovery of endotoxins by richard pfeiffer, such bacterial product was associated to many severe disorders produced by an overwhelming inflammatory response and often resulting in endotoxic shock and multiple organ failure. however, recent clinical and basic sciences investigations claimed some beneficial roles of typical as well as atypical endotoxins. the aim of this paper is to focus on recent data supporting a beneficial activity of both typical and atypical endotoxins. such n ...201222665953
passage of campylobacter jejuni through the chicken reservoir or mice promotes phase variation in contingency genes cj0045 and cj0170 that strongly associates with colonization and disease in a mouse model.human illness due to camplyobacter jejuni infection is closely associated with consumption of poultry products. we previously demonstrated a 50 % shift in allele frequency (phase variation) in contingency gene cj1139 (wlan) during passage of c. jejuni nctc11168 populations through ross 308 broiler chickens. we hypothesized that phase variation in contingency genes during chicken passage could promote subsequent colonization and disease in humans. to test this hypothesis, we passaged c. jejuni st ...201222343355
the campylobacter jejuni ciac virulence protein is secreted from the flagellum and delivered to the cytosol of host cells.campylobacter jejuni is a leading cause of bacterial gastroenteritis worldwide. acute c. jejuni-mediated disease (campylobacteriosis) involves c. jejuni invasion of host epithelial cells using adhesins (e.g., cadf and flpa) and secreted proteins [e.g., the campylobacter invasion antigens (cia)]. the genes encoding the cia proteins are up-regulated upon co-culture of c. jejuni with epithelial cells. one of the cia proteins, ciac, is required for maximal invasion of host cells by c. jejuni. previo ...201222919623
insights from genomic comparisons of genetically monomorphic bacterial pathogens.some of the most deadly bacterial diseases, including leprosy, anthrax and plague, are caused by bacterial lineages with extremely low levels of genetic diversity, the so-called 'genetically monomorphic bacteria'. it has only become possible to analyse the population genetics of such bacteria since the recent advent of high-throughput comparative genomics. the genomes of genetically monomorphic lineages contain very few polymorphic sites, which often reflect unambiguous clonal genealogies. some ...201222312053
peptide markers of aminoacyl trna synthetases facilitate taxa counting in metagenomic data.taxa counting is a major problem faced by analysis of metagenomic data. the most popular method relies on analysis of 16s rrna sequences, but some studies employ also protein based analyses. it would be advantageous to have a method that is applicable directly to short sequences, of the kind extracted from samples in modern metagenomic research. this is achieved by the technique proposed here.201222325056
o-antigen and core carbohydrate of vibrio fischeri lipopolysaccharide: composition and analysis of their role in euprymna scolopes light organ colonization.vibrio fischeri exists in a symbiotic relationship with the hawaiian bobtail squid, euprymna scolopes, where the squid provides a home for the bacteria, and the bacteria in turn provide camouflage that helps protect the squid from night-time predators. like other gram-negative organisms, v. fischeri expresses lipopolysaccharide (lps) on its cell surface. the structure of the o-antigen and the core components of the lps and their possible role in colonization of the squid have not previously been ...201222247546
delineation of structural domains and identification of functionally important residues in dna repair enzyme exonuclease vii.exonuclease vii (exovii) is a bacterial nuclease involved in dna repair and recombination that hydrolyses single-stranded dna. exovii is composed of two subunits: large xsea and small xseb. thus far, little was known about the molecular structure of exovii, the interactions between xsea and xseb, the architecture of the nuclease active site or its mechanism of action. we used bioinformatics methods to predict the structure of xsea, which revealed four domains: an n-terminal ob-fold domain, a mid ...201222718974
protein export according to schedule: architecture, assembly, and regulation of type iii secretion systems from plant- and animal-pathogenic bacteria.flagellar and translocation-associated type iii secretion (t3s) systems are present in most gram-negative plant- and animal-pathogenic bacteria and are often essential for bacterial motility or pathogenicity. the architectures of the complex membrane-spanning secretion apparatuses of both systems are similar, but they are associated with different extracellular appendages, including the flagellar hook and filament or the needle/pilus structures of translocation-associated t3s systems. the needle ...201222688814
chaperone-usher pathways: diversity and pilus assembly mechanism.up to eight different types of secretion systems, and several more subtypes, have been described in gram-negative bacteria. here, we focus on the diversity and assembly mechanism of one of the best-studied secretion systems, the widespread chaperone-usher pathway known to assemble and secrete adhesive surface structures, called pili or fimbriae, which play essential roles in targeting bacterial pathogens to the host.201222411982
characterization of transcription factors that regulate the type iv secretion system and riboflavin biosynthesis in wolbachia of brugia malayi.the human filarial parasite brugia malayi harbors an endosymbiotic bacterium wolbachia (wbm) that is required for parasite survival. consequently, targeting wbm is a promising approach for anti-filarial drug development. the type iv secretion system (t4ss) plays an important role in bacteria-host interactions and is under stringent regulation by transcription factors. in wbm, most t4ss genes are contained in two operons. we show the wbm is active since the essential assembly factor virb8-1, is t ...201223251587
a marr-type regulator directly activates transcription from the brucella abortus virb promoter by sharing a redundant role with hutc.type iv secretion systems (t4ss) are multiprotein structures that direct the translocation of specific molecules across the bacterial cell envelope. as in other bacteria, pathogenicity of the genus brucella essentially depends on the integrity of the t4ss-encoding virb operon, whose expression is regulated by multiple transcription factors belonging to different families. previously, we identified ihf and hutc, two direct regulators of the virb genes that were isolated from total protein extract ...201223002224
solitary restriction endonucleases in prokaryotic genomes.prokaryotic restriction-modification (r-m) systems defend the host cell from the invasion of a foreign dna. they comprise two enzymatic activities: specific dna cleavage activity and dna methylation activity preventing cleavage. typically, these activities are provided by two separate enzymes: a dna methyltransferase (mtase) and a restriction endonuclease (re). in the absence of a corresponding mtase, an re of type ii r-m system is highly toxic for the cell. genes of the r-m system are linked in ...201222965118
vaxjo: a web-based vaccine adjuvant database and its application for analysis of vaccine adjuvants and their uses in vaccine development.vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. basic information of a vaccine adjuvant stored in vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. reliable references are curated and cited. bioin ...201222505817
classical labeling of bacterial pathogens according to their lifestyle in the host: inconsistencies and alternatives.an ample understanding of the complex interactions between host and pathogen will improve our ability to develop new prophylactic and therapeutic measures against infection. precise classification of infectious agents in regards to their infective lifestyles in the host and corresponding pathogenic implications are required because clear concepts are essential to plan fruitful research. classically, pathogenic bacteria are classified as extracellular, facultative intracellular, and obligate intr ...201222393329
mining the sinorhizobium meliloti transportome to develop fret biosensors for sugars, dicarboxylates and cyclic polyols.förster resonance energy transfer (fret) biosensors are powerful tools to detect biologically important ligands in real time. currently fret bisosensors are available for twenty-two compounds distributed in eight classes of chemicals (two pentoses, two hexoses, two disaccharides, four amino acids, one nucleobase, two nucleotides, six ions and three phytoestrogens). to expand the number of available fret biosensors we used the induction profile of the sinorhizobium meliloti transportome to system ...201223028462
molecular characterization of nad+-dependent dna ligase from wolbachia endosymbiont of lymphatic filarial parasite brugia malayi.the lymphatic filarial parasite, brugia malayi contains wolbachia endobacteria that are essential for development, viability and fertility of the parasite. therefore, wolbachial proteins have been currently seen as the potential antifilarial drug targets. nad(+)-dependent dna ligase is characterized as a promising drug target in several organisms due to its crucial, indispensable role in dna replication, recombination and dna repair. we report here the cloning, expression and purification of nad ...201222815933
factors influencing the diversity of iron uptake systems in aquatic microorganisms.iron (fe) is an essential micronutrient for many processes in all living cells. dissolved fe (dfe) concentrations in the ocean are of the order of a few nm, and fe is often a factor limiting primary production. bioavailability of fe in aquatic environments is believed to be primarily controlled through chelation by fe-binding ligands. marine microbes have evolved different mechanisms to cope with the scarcity of bioavailable dfe. gradients in dfe concentrations and diversity of the fe-ligand poo ...201223087680
identification of c-terminal hydrophobic residues important for dimerization and all known functions of parb of pseudomonas aeruginosa.the parb protein of pseudomonas aeruginosa is important for growth, cell division, nucleoid segregation and different types of motility. to further understand its function we have demonstrated a vital role of the hydrophobic residues in the c terminus of parb(p.a.). by in silico modelling of the c-terminal domain (amino acids 242-290) the hydrophobic residues l282, v285 and i289 (but not l286) are engaged in leucine-zipper-like structure formation, whereas the charged residues r290 and q266 are ...201222322962
roles of long and short replication initiation proteins in the fate of incp-1 plasmids.broad-host-range incp-1 plasmids generally encode two replication initiation proteins, trfa1 and trfa2. trfa2 is produced from an internal translational start site within trfa1. while trfa1 was previously shown to be essential for replication in pseudomonas aeruginosa, its role in other bacteria within its broad host range has not been established. to address the role of trfa1 and trfa2 in other hosts, efficiency of transformation, plasmid copy number (pcn), and plasmid stability were first comp ...201222228734
a multilocus sequence typing scheme implies population structure and reveals several putative novel achromobacter species.the genus achromobacter currently is comprised of seven species, including achromobacter xylosoxidans, an opportunistic and nosocomial pathogen that displays broad-spectrum antimicrobial resistance and is recognized as causing chronic respiratory tract infection in persons with cystic fibrosis (cf). to enable strain typing for global epidemiologic investigations, to clarify the taxonomy of "achromobacter-like" strains, and to elucidate the population structure of this genus, we developed a genus ...201222785192
burkholderia cenocepacia type vi secretion system mediates escape of type ii secreted proteins into the cytoplasm of infected macrophages.burkholderia cenocepacia is an opportunistic pathogen that survives intracellularly in macrophages and causes serious respiratory infections in patients with cystic fibrosis. we have previously shown that bacterial survival occurs in bacteria-containing membrane vacuoles (bccvs) resembling arrested autophagosomes. intracellular bacteria stimulate il-1β secretion in a caspase-1-dependent manner and induce dramatic changes to the actin cytoskeleton and the assembly of the nadph oxidase complex ont ...201222848580
targeting pan-resistant bacteria with antibodies to a broadly conserved surface polysaccharide expressed during infection.new therapeutic targets for antibiotic-resistant bacterial pathogens are desperately needed. the bacterial surface polysaccharide poly-β-(1-6)-n-acetyl-glucosamine (pnag) mediates biofilm formation by some bacterial species, and antibodies to pnag can confer protective immunity. by analyzing sequenced genomes, we found that potentially multidrug-resistant bacterial species such as klebsiella pneumoniae, enterobacter cloacae, stenotrophomonas maltophilia, and the burkholderia cepacia complex (bcc ...201222448004
glioblastoma multiforme: novel therapeutic approaches.the current therapy for glioblastoma multiforme involves total surgical resection followed by combination of radiation therapy and temozolomide. unfortunately, the efficacy for such current therapy is limited, and newer approaches are sorely needed to treat this deadly disease. we have recently described the isolation of bacterial proteins and peptides with anticancer activity. in phase i human clinical trials, one such peptide, p28, derived from a bacterial protein azurin, showed partial and co ...201222462021
the chemical composition of endotoxin isolated from intestinal strain of desulfovibrio desulfuricans.desulfovibrio desulfuricans anaerobes are constituents of human alimentary tract microflora. there are suggestions that they take part in the pathogenesis of periodontitis and some gastrointestinal inflammatory disorders, such as ulcerative colitis or crohn's disease. endotoxin is one of gram-negative bacteria cellular components that influence these microorganisms pathogenicity. endotoxin is a lipid-polisaccharide heteropolymer consisting of three elements: lipid a, core oligosaccharide, and o- ...201222629175
developing insights into the mechanisms of evolution of bacterial pathogens from whole-genome sequences.evolution of bacterial pathogen populations has been detected in a variety of ways including phenotypic tests, such as metabolic activity, reaction to antisera and drug resistance and genotypic tests that measure variation in chromosome structure, repetitive loci and individual gene sequences. while informative, these methods only capture a small subset of the total variation and, therefore, have limited resolution. advances in sequencing technologies have made it feasible to capture whole-genom ...201223075447
atomic force and super-resolution microscopy support a role for lapa as a cell-surface biofilm adhesin of pseudomonas fluorescens.pseudomonas fluorescence pf0-1 requires the large repeat protein lapa for stable surface attachment. this study presents direct evidence that lapa is a cell-surface-localized adhesin. atomic force microscopy (afm) revealed a significant 2-fold reduction in adhesion force for mutants lacking the lapa protein on the cell surface compared to the wild-type strain. deletion of lapg, a gene encoding a periplasmic cysteine protease that functions to release lapa from the cell surface, resulted in a 2-f ...201223064158
a novel virulence strategy for pseudomonas aeruginosa mediated by an autotransporter with arginine-specific aminopeptidase activity.the opportunistic human pathogen, pseudomonas aeruginosa, is a major cause of infections in chronic wounds, burns and the lungs of cystic fibrosis patients. the p. aeruginosa genome encodes at least three proteins exhibiting the characteristic three domain structure of autotransporters, but much remains to be understood about the functions of these three proteins and their role in pathogenicity. autotransporters are the largest family of secreted proteins in gram-negative bacteria, and those cha ...201222927813
cellular levels and binding of c-di-gmp control subcellular localization and activity of the vibrio cholerae transcriptional regulator vpst.the second messenger, cyclic diguanylate (c-di-gmp), regulates diverse cellular processes in bacteria. c-di-gmp is produced by diguanylate cyclases (dgcs), degraded by phosphodiesterases (pdes), and receptors couple c-di-gmp production to cellular responses. in many bacteria, including vibrio cholerae, multiple dgcs and pdes contribute to c-di-gmp signaling, and it is currently unclear whether the compartmentalization of c-di-gmp signaling components is required to mediate c-di-gmp signal transd ...201222654664
plastid genetic engineering in solanaceae.plastid genetic engineering has come of age, becoming today an attractive alternative approach for the expression of foreign genes, as it offers several advantages over nuclear transformants. significant progress has been made in plastid genetic engineering in tobacco and other solanaceae plants, through the use of improved regeneration procedures and transformation vectors with efficient promoters and untranslated regions. many genes encoding for industrially important proteins and vaccines, as ...201222395455
pseudomonas biofilm matrix composition and niche biology.biofilms are a predominant form of growth for bacteria in the environment and in the clinic. critical for biofilm development are adherence, proliferation, and dispersion phases. each of these stages includes reinforcement by, or modulation of, the extracellular matrix. pseudomonas aeruginosa has been a model organism for the study of biofilm formation. additionally, other pseudomonas species utilize biofilm formation during plant colonization and environmental persistence. pseudomonads produce ...201222212072
the drosophila melanogaster host model.the deleterious and sometimes fatal outcomes of bacterial infectious diseases are the net result of the interactions between the pathogen and the host, and the genetically tractable fruit fly, drosophila melanogaster, has emerged as a valuable tool for modeling the pathogen-host interactions of a wide variety of bacteria. these studies have revealed that there is a remarkable conservation of bacterial pathogenesis and host defence mechanisms between higher host organisms and drosophila. this rev ...201222368770
inferring the evolutionary history of incp-1 plasmids despite incongruence among backbone gene trees.plasmids of the incompatibility group incp-1 can transfer and replicate in many genera of the proteobacteria. they are composed of backbone genes that encode a variety of essential functions and accessory genes that have implications for human health and environmental remediation. although it is well understood that the accessory genes are transferred horizontally between plasmids, recent studies have also provided examples of recombination in the backbone genes of incp-1 plasmids. as a conseque ...201222936717
inferring the evolutionary history of incp-1 plasmids despite incongruence among backbone gene trees.plasmids of the incompatibility group incp-1 can transfer and replicate in many genera of the proteobacteria. they are composed of backbone genes that encode a variety of essential functions and accessory genes that have implications for human health and environmental remediation. although it is well understood that the accessory genes are transferred horizontally between plasmids, recent studies have also provided examples of recombination in the backbone genes of incp-1 plasmids. as a conseque ...201222936717
novel gain of function approaches for vaccine candidate identification in burkholderia pseudomallei.the gram-negative bacterium burkholderia pseudomallei is a serious environmental pathogen and the causative agent of the often fatal melioidosis. disease occurs following exposure to contaminated water or soil, usually through cuts in the skin or via inhalation. however, the underlying mechanisms of pathogenicity remain poorly understood. b. pseudomallei is endemic to south east asia and northern australia where infections are associated with antibiotic resistance and high mortality rates. categ ...201223316481
novel gain of function approaches for vaccine candidate identification in burkholderia pseudomallei.the gram-negative bacterium burkholderia pseudomallei is a serious environmental pathogen and the causative agent of the often fatal melioidosis. disease occurs following exposure to contaminated water or soil, usually through cuts in the skin or via inhalation. however, the underlying mechanisms of pathogenicity remain poorly understood. b. pseudomallei is endemic to south east asia and northern australia where infections are associated with antibiotic resistance and high mortality rates. categ ...201223316481
bacterial toxin effector-membrane targeting: outside in, then back again.pathogenic bacteria utilize multiple approaches to establish infection and mediate their toxicity to eukaryotic cells. dedicated protein machines deposit toxic effectors directly inside the host, whereas secreted toxins must enter cells independently of other bacterial components. regardless of how they reach the cytosol, these bacterial proteins must accurately identify their intracellular target before they can manipulate the host cell to benefit their associated bacteria. within eukaryotic ce ...201222919666
the bacterium pantoea stewartii uses two different type iii secretion systems to colonize its plant host and insect vector.plant- and animal-pathogenic bacteria utilize phylogenetically distinct type iii secretion systems (t3ss) that produce needle-like injectisomes or pili for the delivery of effector proteins into host cells. pantoea stewartii subsp. stewartii (herein referred to as p. stewartii), the causative agent of stewart's bacterial wilt and leaf blight of maize, carries phylogenetically distinct t3sss. in addition to an hrc-hrp t3ss, known to be essential for maize pathogenesis, p. stewartii has a second t ...201222773631
srfj, a salmonella type iii secretion system effector regulated by phop, rcsb, and iolr.virulence-related type iii secretion systems are present in many gram-negative bacterial pathogens. these complex devices translocate proteins, called effectors, from the bacterium into the eukaryotic host cell. here, we identify the product of srfj, a salmonella enterica serovar typhimurium gene regulated by ssrb, as a new substrate of the type iii secretion system encoded by salmonella pathogenicity island 2. the n-terminal 20-amino-acid segment of srfj was recognized as a functional secretion ...201222661691
rapa2 is a calcium-binding lectin composed of two highly conserved cadherin-like domains that specifically recognize rhizobium leguminosarum acidic exopolysaccharides.in silico analyses have revealed a conserved protein domain (chdl) widely present in bacteria that has significant structural similarity to eukaryotic cadherins. a chdl domain was shown to be present in rapa, a protein that is involved in autoaggregation of rhizobium cells, biofilm formation, and adhesion to plant roots as shown by us and others. structural similarity to cadherins suggested calcium-dependent oligomerization of chdl domains as a mechanistic basis for rapa action. here we show by ...201223235153
rapa2 is a calcium-binding lectin composed of two highly conserved cadherin-like domains that specifically recognize rhizobium leguminosarum acidic exopolysaccharides.in silico analyses have revealed a conserved protein domain (chdl) widely present in bacteria that has significant structural similarity to eukaryotic cadherins. a chdl domain was shown to be present in rapa, a protein that is involved in autoaggregation of rhizobium cells, biofilm formation, and adhesion to plant roots as shown by us and others. structural similarity to cadherins suggested calcium-dependent oligomerization of chdl domains as a mechanistic basis for rapa action. here we show by ...201223235153
the structure of mlc titration factor a (mtfa/yeei) reveals a prototypical zinc metallopeptidase related to anthrax lethal factor.mtfa of escherichia coli (formerly yeei) was previously identified as a regulator of the phosphoenolpyruvate (pep)-dependent:glucose phosphotransferase system. mtfa homolog proteins are highly conserved, especially among beta- and gammaproteobacteria. we determined the crystal structures of the full-length mtfa apoenzyme from klebsiella pneumoniae and its complex with zinc (holoenzyme) at 2.2 and 1.95 å, respectively. mtfa contains a conserved h(149)e(150)xxh(153)+e(212)+y(205) metallopeptidase ...201222467785
expression of multidrug resistance efflux pump gene nora is iron responsive in staphylococcus aureus.staphylococcus aureus utilizes efflux transporter nora to pump out a wide range of structurally dissimilar drugs, conferring low-level multidrug resistance. the regulation of nora expression has yet to be fully understood although past studies have revealed that this gene is under the control of the global transcriptional regulator mgra and the two-component system arlrs. to identify additional regulators of nora, we screened a transposon library in strain newman expressing the transcriptional f ...201222267518
detection of spatial correlations in protein structures and molecular complexes.protein structures are frequently related by spectacular and often surprising similarities. structural correlations among protein chains are routinely detected by various structure-matching techniques, but the comparison of oligomers and molecular complexes is largely uncharted territory. here we solve the structure-matching problem for oligomers and large molecular aggregates, including the largest molecular complexes known today. we provide several challenging examples that cannot be handled b ...201222483118
evolution of burkholderia pseudomallei in recurrent melioidosis.burkholderia pseudomallei, the etiologic agent of human melioidosis, is capable of causing severe acute infection with overwhelming septicemia leading to death. a high rate of recurrent disease occurs in adult patients, most often due to recrudescence of the initial infecting strain. pathogen persistence and evolution during such relapsing infections are not well understood. bacterial cells present in the primary inoculum and in late infections may differ greatly, as has been observed in chronic ...201222615773
evolution of conjugation and type iv secretion systems.genetic exchange by conjugation is responsible for the spread of resistance, virulence, and social traits among prokaryotes. recent works unraveled the functioning of the underlying type iv secretion systems (t4ss) and its distribution and recruitment for other biological processes (exaptation), notably pathogenesis. we analyzed the phylogeny of key conjugation proteins to infer the evolutionary history of conjugation and t4ss. we show that single-stranded dna (ssdna) and double-stranded dna (ds ...201222977114
evolution of conjugation and type iv secretion systems.genetic exchange by conjugation is responsible for the spread of resistance, virulence, and social traits among prokaryotes. recent works unraveled the functioning of the underlying type iv secretion systems (t4ss) and its distribution and recruitment for other biological processes (exaptation), notably pathogenesis. we analyzed the phylogeny of key conjugation proteins to infer the evolutionary history of conjugation and t4ss. we show that single-stranded dna (ssdna) and double-stranded dna (ds ...201222977114
the legionella icmsw complex directly interacts with dotl to mediate translocation of adaptor-dependent substrates.legionella pneumophila is a gram-negative bacterium that replicates within human alveolar macrophages by evasion of the host endocytic pathway through the formation of a replicative vacuole. generation of this vacuole is dependent upon the secretion of over 275 effector proteins into the host cell via the dot/icm type ivb secretion system (t4ss). the type iv coupling protein (t4cp) subcomplex, consisting of dotl, dotm, dotn, icms and icmw, was recently defined. dotl is proposed to be the t4cp of ...201223028312
subversion of cell signaling by pathogens.pathogens exploit several eukaryotic signaling pathways during an infection. they have evolved specific effectors and toxins to hijack host cell machinery for their own benefit. signaling molecules are preferentially targeted by pathogens because they globally regulate many cellular processes. both viruses and bacteria manipulate and control pathways that regulate host cell survival and shape, including mapk signaling, g-protein signaling, signals controlling cytoskeletal dynamics, and innate im ...201222952390
comparison of three multiplex pcr assays for the detection of respiratory viral infections: evaluation of xtag respiratory virus panel fast assay, respifinder 19 assay and respifinder smart 22 assay.a broad spectrum of pathogens is causative for respiratory tract infections, but symptoms are mostly similar. therefore, the identification of the causative viruses and bacteria is only feasible using multiplex pcr or several monoplex pcr tests in parallel.201222828244
identification of leishmania infantum chagasi proteins in urine of patients with visceral leishmaniasis: a promising antigen discovery approach of vaccine candidates.visceral leishmaniasis (vl) is a serious lethal parasitic disease caused by leishmania donovani in asia and by leishmania infantum chagasi in southern europe and south america. vl is endemic in 47 countries with an annual incidence estimated to be 500,000 cases. this high incidence is due in part to the lack of an efficacious vaccine. here, we introduce an innovative approach to directly identify parasite vaccine candidate antigens that are abundantly produced in vivo in humans with vl. we combi ...201222443237
structure of the virb4 atpase, alone and bound to the core complex of a type iv secretion system.type iv secretion (t4s) systems mediate the transfer of proteins and dna across the cell envelope of bacteria. these systems play important roles in bacterial pathogenesis and in horizontal transfer of antibiotic resistance. the virb4 atpase of the t4s system is essential for both the assembly of the system and substrate transfer. in this article, we present the crystal structure of the c-terminal domain of thermoanaerobacter pseudethanolicus virb4. this structure is strikingly similar to that o ...201222745169
pathogen- and host-directed anti-inflammatory activities of macrolide antibiotics.macrolide antibiotics possess several, beneficial, secondary properties which complement their primary antimicrobial activity. in addition to high levels of tissue penetration, which may counteract seemingly macrolide-resistant bacterial pathogens, these agents also possess anti-inflammatory properties, unrelated to their primary antimicrobial activity. macrolides target cells of both the innate and adaptive immune systems, as well as structural cells, and are beneficial in controlling harmful i ...201222778497
characteristics of suppressor macrophages induced by mycobacterial and protozoal infections in relation to alternatively activated m2 macrophages.in the advanced stages of mycobacterial infections, host immune systems tend to change from a th1-type to th2-type immune response, resulting in the abrogation of th1 cell- and macrophage-mediated antimicrobial host protective immunity. notably, this type of immune conversion is occasionally associated with the generation of certain types of suppressor macrophage populations. during the course of mycobacterium tuberculosis (mtb) and mycobacterium avium-intracellulare complex (mac) infections, th ...201222666284
assembly and mechanisms of bacterial type iv secretion machines.type iv secretion occurs across a wide range of prokaryotic cell envelopes: gram-negative, gram-positive, cell wall-less bacteria and some archaea. this diversity is reflected in the heterogeneity of components that constitute the secretion machines. macromolecules are secreted in an atp-dependent process using an envelope-spanning multi-protein channel. similar to the type iii systems, this apparatus extends beyond the cell surface as a pilus structure important for direct contact and penetrati ...201222411979
the impact of bacterial and viral co-infection in severe influenza.many questions remain concerning the burden, risk factors and impact of bacterial and viral co-infection in patients with pandemic influenza admitted to the intensive care unit (icu).201222487223
the impact of bacterial and viral co-infection in severe influenza.many questions remain concerning the burden, risk factors and impact of bacterial and viral co-infection in patients with pandemic influenza admitted to the intensive care unit (icu).201222487223
strategies of exploitation of mammalian reservoirs by bartonella species.numerous mammal species, including domestic and wild animals such as ruminants, dogs, cats and rodents, as well as humans, serve as reservoir hosts for various bartonella species. some of those species that exploit non-human mammals as reservoir hosts have zoonotic potential. our understanding of interactions between bartonellae and reservoir hosts has been greatly improved by the development of animal models for infection and the use of molecular tools allowing large scale mutagenesis of barton ...201222369683
comparison of sputum and nasopharyngeal swab specimens for molecular diagnosis of mycoplasma pneumoniae, chlamydophila pneumoniae, and legionella pneumophila.differentiation of atypical pathogens is important for community-acquired pneumonia (cap). in this study, we compared sputum and nasopharyngeal swabs (nps) for use in detection of mycoplasma pneumoniae (mp), chlamydophila pneumoniae (cp), and legionella pneumophila (lp), using seeplex pneumobacter ace detection assay (pneumobacter; seegene).201222389880
the dna exonucleases of escherichia coli.dna exonucleases, enzymes that hydrolyze phosphodiester bonds in dna from a free end, play important cellular roles in dna repair, genetic recombination and mutation avoidance in all organisms. this article reviews the structure, biochemistry, and biological functions of the 17 exonucleases currently identified in the bacterium escherichia coli. these include the exonucleases associated with dna polymerases i (pola), ii (polb), and iii (dnaq/mutd); exonucleases i (xona/sbcb), iii (xtha), iv, vii ...201126442508
snapshot of spatio-temporal cytokine responses to single and co-infections with helminths and bacteria.cytokines play a key role in maintaining communication between organs and in so doing modulate the interaction between concurrent infections. the extent of these effects depends on the properties of the organ infected and the intensity and type of infections. to determine systemic bystander effects among organs, ifn-γ, il-4 and il-10 gene expression was quantified at 7 days post-challenge in directly infected and uninfected organs during single and co-infections with the respiratory bacterium bo ...201124371558
immunoglobulin a: a next generation of therapeutic antibodies?although immunoglobulin (ig) a is commonly recognized as the most prevalent antibody subclass at mucosal sites with an important role in mucosal defense, its potential as a therapeutic monoclonal antibody is less well known. however, iga has multifaceted anti-, non-, and pro-inflammatory functions that can be exploited for different immunotherapeutical strategies, which will be the focus of this review.201121691145
natural killer (nk) cells in antibacterial innate immunity: angels or devils?natural killer (nk) cells were first described as immune leukocytes that could kill tumor cells and soon after were reported to kill virus-infected cells. in the mid-1980s, 10 years after their discovery, nk cells were also demonstrated to contribute to the fight against bacterial infection, particularly because of crosstalk with other leukocytes. a wide variety of immune cells are now recognized to interact with nk cells through the production of cytokines such as interleukin (il)-2, il-12, il- ...201122105606
natural killer (nk) cells in antibacterial innate immunity: angels or devils?natural killer (nk) cells were first described as immune leukocytes that could kill tumor cells and soon after were reported to kill virus-infected cells. in the mid-1980s, 10 years after their discovery, nk cells were also demonstrated to contribute to the fight against bacterial infection, particularly because of crosstalk with other leukocytes. a wide variety of immune cells are now recognized to interact with nk cells through the production of cytokines such as interleukin (il)-2, il-12, il- ...201122105606
assembly of outer membrane β-barrel proteins: the bam complex.the major class of integral proteins found in the outer membrane (om) of e. coli and salmonella adopt a β-barrel conformation (omps). omps are synthesized in the cytoplasm with a typical signal sequence at the amino terminus, which directs them to the secretion machinery (secyeg) located in the inner membrane for translocation to the periplasm. chaperones such as sura, or degp and skp, escort these proteins across the aqueous periplasm protecting them from aggregation. the chaperones then delive ...201126442509
complexes formed in solution between vanadium(iv)/(v) and the cyclic dihydroxamic acid putrebactin or linear suberodihydroxamic acid.an aerobic solution prepared from v(iv) and the cyclic dihydroxamic acid putrebactin (pbh(2)) in 1:1 h(2)o/ch(3)oh at ph = 2 turned from blue to orange and gave a signal in the positive ion electrospray ionization mass spectrometry (esi-ms) at m/z(obs) 437.0 attributed to the monooxov(v) species [v(v)o(pb)](+) ([c(16)h(26)n(4)o(7)v](+), m/z(calc) 437.3). a solution prepared as above gave a signal in the (51)v nmr spectrum at δ(v )= -443.3 ppm (vocl(3), δ(v) = 0 ppm) and was electron paramagnetic ...201121627146
hospital epidemiology and infection control in acute-care settings.health care-associated infections (hais) have become more common as medical care has grown more complex and patients have become more complicated. hais are associated with significant morbidity, mortality, and cost. growing rates of hais alongside evidence suggesting that active surveillance and infection control practices can prevent hais led to the development of hospital epidemiology and infection control programs. the role for infection control programs has grown and continues to grow as rat ...201121233510
inadequacies of minimum spanning trees in molecular epidemiology.minimum spanning trees (msts) are frequently used in molecular epidemiology research to estimate relationships among individual strains or isolates. nevertheless, there are significant caveats to mst algorithms that have been largely ignored in molecular epidemiology studies and that have the potential to confound or alter the interpretation of the results of those analyses. specifically, (i) presenting a single, arbitrarily selected mst illustrates only one of potentially many equally optimal s ...201121849692
comparative genomics evidence that only protein toxins are tagging bad bugs.the term toxin was introduced by roux and yersin and describes macromolecular substances that, when produced during infection or when introduced parenterally or orally, cause an impairment of physiological functions that lead to disease or to the death of the infected organism. long after the discovery of toxins, early genetic studies on bacterial virulence demonstrated that removing a certain number of genes from pathogenic bacteria decreases their capacity to infect hosts. each of the removed ...201122919573
genomes of the most dangerous epidemic bacteria have a virulence repertoire characterized by fewer genes but more toxin-antitoxin modules.we conducted a comparative genomic study based on a neutral approach to identify genome specificities associated with the virulence capacity of pathogenic bacteria. we also determined whether virulence is dictated by rules, or if it is the result of individual evolutionary histories. we systematically compared the genomes of the 12 most dangerous pandemic bacteria for humans ("bad bugs") to their closest non-epidemic related species ("controls").201121437250
defining pathogenic bacterial species in the genomic era.actual definitions of bacterial species are limited due to the current criteria of definition and the use of restrictive genetic tools. the 16s ribosomal rna sequence, for example, has been widely used as a marker for phylogenetic analyses; however, its use often leads to misleading species definitions. according to the first genetic studies, removing a certain number of genes from pathogenic bacteria removes their capacity to infect hosts. however, more recent studies have demonstrated that the ...201121687765
defining pathogenic bacterial species in the genomic era.actual definitions of bacterial species are limited due to the current criteria of definition and the use of restrictive genetic tools. the 16s ribosomal rna sequence, for example, has been widely used as a marker for phylogenetic analyses; however, its use often leads to misleading species definitions. according to the first genetic studies, removing a certain number of genes from pathogenic bacteria removes their capacity to infect hosts. however, more recent studies have demonstrated that the ...201121687765
molecular evolution of urea amidolyase and urea carboxylase in fungi.urea amidolyase breaks down urea into ammonia and carbon dioxide in a two-step process, while another enzyme, urease, does this in a one step-process. urea amidolyase has been found only in some fungal species among eukaryotes. it contains two major domains: the amidase and urea carboxylase domains. a shorter form of urea amidolyase is known as urea carboxylase and has no amidase domain. eukaryotic urea carboxylase has been found only in several fungal species and green algae. in order to elucid ...201121447149
cancer vaccines and carbohydrate epitopes.tumor-associated carbohydrate antigens (taca) result from the aberrant glycosylation that is seen with transformation to a tumor cell. the carbohydrate antigens that have been found to be tumor-associated include the mucin related tn, sialyl tn, and thomsen-friedenreich antigens, the blood group lewis related lewis(y), sialyl lewis(x) and sialyl lewis(a), and lewis(x) (also known as stage-specific embryonic antigen-1, ssea-1), the glycosphingolipids globo h and stage-specific embryonic antigen-3 ...201121964054
antimicrobial prophylaxis in adults.antimicrobial prophylaxis is commonly used by clinicians for the prevention of numerous infectious diseases, including herpes simplex infection, rheumatic fever, recurrent cellulitis, meningococcal disease, recurrent uncomplicated urinary tract infections in women, spontaneous bacterial peritonitis in patients with cirrhosis, influenza, infective endocarditis, pertussis, and acute necrotizing pancreatitis, as well as infections associated with open fractures, recent prosthetic joint placement, a ...201121719623
vaccine herd effect.vaccination ideally protects susceptible populations at high risk for complications of the infection. however, vaccines for these subgroups do not always provide sufficient effectiveness. the herd effect or herd immunity is an attractive way to extend vaccine benefits beyond the directly targeted population. it refers to the indirect protection of unvaccinated persons, whereby an increase in the prevalence of immunity by the vaccine prevents circulation of infectious agents in susceptible popula ...201121604922
dendritic cell control of tolerogenic responses.one of the most fundamental problems in immunology is the seemingly schizophrenic ability of the immune system to launch robust immunity against pathogens, while acquiring and maintaining a state of tolerance to the body's own tissues and the trillions of commensal microorganisms and food antigens that confront it every day. a fundamental role for the innate immune system, particularly dendritic cells (dcs), in orchestrating immunological tolerance has been appreciated, but emerging studies have ...201121488899
pseudomonas aeruginosa pily1 binds integrin in an rgd- and calcium-dependent manner.pily1 is a type iv pilus (tfp)-associated protein from the opportunistic pathogen pseudomonas aeruginosa that shares functional similarity with related proteins in infectious neisseria and kingella species. previous data have shown that pily1 acts as a calcium-dependent pilus biogenesis factor necessary for twitching motility with a specific calcium binding site located at amino acids 850-859 in the 1,163 residue protein. in addition to motility, pily1 is also thought to play an important role i ...201122242136
natural killer (nk) and nk-like cells at mucosal epithelia: mediators of anti-microbial defense and maintenance of tissue integrity.natural killer (nk) cells are innate lymphocytes that play important roles in the defense against microbial pathogens through secretion of ifn-γ and recognition and lysis of virally or bacterially infected host cells. a recently identified population of nk-like cells that shares characteristics of both nk cells and lymphoid tissue inducer (lti) cells promotes innate immune responses in epithelial tissue through the secretion of il-22. in contrast to classical nk cells, nk-like cells are localize ...201124516732
high burden of non-influenza viruses in influenza-like illness in the early weeks of h1n1v epidemic in france.influenza-like illness (ili) may be caused by a variety of pathogens. clinical observations are of little help to recognise myxovirus infection and implement appropriate prevention measures. the limited use of molecular tools underestimates the role of other common pathogens.201121858150
application of taqman low-density arrays for simultaneous detection of multiple respiratory pathogens.the large and growing number of viral and bacterial pathogens responsible for respiratory infections poses a challenge for laboratories seeking to provide rapid and comprehensive pathogen identification. we evaluated a novel application of the taqman low-density array (tlda) cards for real-time pcr detection of 21 respiratory-pathogen targets. the performance of the tlda was compared to that of individual real-time pcr (irtp) assays with the same primers and probes using (i) nucleic acids extrac ...201121471348
are we ready for novel detection methods to treat respiratory pathogens in hospital-acquired pneumonia?hospital-acquired pneumonia represents one of the most difficult treatment challenges in infectious diseases. many studies suggest that the timely administration of appropriate, pathogen-directed therapy can be lifesaving. because results of culture and antimicrobial susceptibility testing can take 48 h or longer, physicians currently rely on clinical, epidemiological, and demographic factors to assist with the choice of empiric therapy for antibiotic-resistant pathogens. at present, a number of ...201121460299
modulation of nf-κb signalling by microbial pathogens.the nuclear factor-κb (nf-κb) family of transcription factors plays a central part in the host response to infection by microbial pathogens, by orchestrating the innate and acquired host immune responses. the nf-κb proteins are activated by diverse signalling pathways that originate from many different cellular receptors and sensors. many successful pathogens have acquired sophisticated mechanisms to regulate the nf-κb signalling pathways by deploying subversive proteins or hijacking the host si ...201121383764
management of patients during and after exacerbations of chronic obstructive pulmonary disease: the role of primary care physicians.current treatments have failed to stem the continuing rise in health care resource use and fatalities associated with exacerbations of chronic obstructive pulmonary disease (copd). reduction of severity and prevention of new exacerbations are therefore important in disease management, especially for patients with frequent exacerbations. acute exacerbation treatment includes short-acting bronchodilators, systemic corticosteroids, and antibiotics if bacterial infections are present. oxygen and/or ...201121941453
ligation of cd46 to cd40 inhibits cd40 signaling in b cells.cd40 induces b cells to switch to ige in the presence of il-4 and up-regulates their expression of the low-affinity receptor for ige, cd23, which promotes the immune response to allergen complexed with ige antibody. cd40 binds to cd40l and to the c4b-binding protein (c4bp) using distinct sites. cd46 is a receptor for the product of activated complement c4b. some microbial antigens bind both c4bp and cd46, potentially bridging cd40 to cd46. in addition, immune complexes containing both c4b and c4 ...201121393637
a computational and experimental study of the regulatory mechanisms of the complement system.the complement system is key to innate immunity and its activation is necessary for the clearance of bacteria and apoptotic cells. however, insufficient or excessive complement activation will lead to immune-related diseases. it is so far unknown how the complement activity is up- or down- regulated and what the associated pathophysiological mechanisms are. to quantitatively understand the modulatory mechanisms of the complement system, we built a computational model involving the enhancement an ...201121283780
multilocus sequence analysis of housekeeping genes and antigenic determinant genes in bordetella pertussis strains isolated in korea.to confirm genotype diversities of clinical isolates of bordetella pertussis and to evaluate the risk of pertussis outbreak in korea.201124159461
recommendation for the use of newly introduced tdap vaccine in korea.pertussis is an acute respiratory infection characterized by paroxysmal cough and inspiratory whoop for over 2 weeks. the incidence of pertussis has decreased markedly after the introduction of dtwp/dtap vaccine, but the incidence of pertussis has increased steadily among young infant and among adolescents and adults in many countries. td vaccine was used in this age group but the increase in pertussis has lead to the development of a tdap vaccine. the tdap vaccine is a td vaccine with a pertuss ...201121738546
anti-n-methyl-d-aspartate receptor encephalitis with serum anti-thyroid antibodies and igm antibodies against epstein-barr virus viral capsid antigen: a case report and one year follow-up.abstract:201122126669
increased ccl24/eotaxin-2 with postnatal ozone exposure in allergen-sensitized infant monkeys is not associated with recruitment of eosinophils to airway mucosa.epidemiology supports a causal link between air pollutant exposure and childhood asthma, but the mechanisms are unknown. we have previously reported that ozone exposure can alter the anatomic distribution of cd25+ lymphocytes in airways of allergen-sensitized infant rhesus monkeys. here, we hypothesized that ozone may also affect eosinophil trafficking to allergen-sensitized infant airways. to test this hypothesis, we measured blood, lavage, and airway mucosa eosinophils in 3-month old monkeys f ...201121945493
targeting the wolbachia cell division protein ftsz as a new approach for antifilarial therapy.the use of antibiotics targeting the obligate bacterial endosymbiont wolbachia of filarial parasites has been validated as an approach for controlling filarial infection in animals and humans. availability of genomic sequences for the wolbachia (wbm) present in the human filarial parasite brugia malayi has enabled genome-wide searching for new potential drug targets. in the present study, we investigated the cell division machinery of wbm and determined that it possesses the essential cell divis ...201122140592
dual infection with bordetella pertussis and mycoplasma pneumoniae in three infants: case reports.studying pertussis-like respiratory infections, we report the cases of three infants with evidence of both bordetella pertussis and mycoplasma pneumoniae. bordetella infection was identified by the real-time polymerase chain reaction (rt-pcr) of nasopharyngeal specimens. neither b. pertussis nor b. parapertussis were recovered on the culture of nasopharyngeal aspirates (npas) from any subjects. m. pneumoniae etiology was diagnosed by culture and rt-pcr. the evolution was fatal for all of the sub ...201121861122
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