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engineering escherichia coli to overproduce aromatic amino acids and derived compounds.the production of aromatic amino acids using fermentation processes with recombinant microorganisms can be an advantageous approach to reach their global demands. in addition, a large array of compounds with alimentary and pharmaceutical applications can potentially be synthesized from intermediates of this metabolic pathway. however, contrary to other amino acids and primary metabolites, the artificial channelling of building blocks from central metabolism towards the aromatic amino acid pathwa ...201425200799
exploring functional contexts of symbiotic sustain within lichen-associated bacteria by comparative omics.symbioses represent a frequent and successful lifestyle on earth and lichens are one of their classic examples. recently, bacterial communities were identified as stable, specific and structurally integrated partners of the lichen symbiosis, but their role has remained largely elusive in comparison to the well-known functions of the fungal and algal partners. we have explored the metabolic potentials of the microbiome using the lung lichen lobaria pulmonaria as the model. metagenomic and proteom ...201425072413
exploring functional contexts of symbiotic sustain within lichen-associated bacteria by comparative omics.symbioses represent a frequent and successful lifestyle on earth and lichens are one of their classic examples. recently, bacterial communities were identified as stable, specific and structurally integrated partners of the lichen symbiosis, but their role has remained largely elusive in comparison to the well-known functions of the fungal and algal partners. we have explored the metabolic potentials of the microbiome using the lung lichen lobaria pulmonaria as the model. metagenomic and proteom ...201425072413
correction of sequence-dependent ambiguous bases (ns) from the 454 pyrosequencing system.pyrosequencing of the 16s ribosomal rna gene (16s) has become one of the most popular methods to assess microbial diversity. pyrosequencing reads containing ambiguous bases (ns) are generally discarded based on the assumptions of their non-sequence-dependent formation and high error rates. however, taxonomic composition differed by removal of reads with ns. we determined whether ns from pyrosequencing occur in a sequence-dependent manner. our reads and the corresponding flow value data revealed ...201424464999
novel reporter for identification of interference with acyl homoserine lactone and autoinducer-2 quorum sensing.two reporter strains were established to identify novel biomolecules interfering with bacterial communication (quorum sensing [qs]). the basic design of these escherichia coli-based systems comprises a gene encoding a lethal protein fused to promoters induced in the presence of qs signal molecules. consequently, these e. coli strains are unable to grow in the presence of the respective qs signal molecules unless a nontoxic qs-interfering compound is present. the first reporter strain designed to ...201525527543
depth and well type related to groundwater microbiological contamination.use of groundwater from private wells in households has increased considerably, owing to a better cost/benefit ratio than that of water provided by local utilities for a fee. however, this water is usually untreated, which makes it a vehicle for diseases. thus, monitoring this water is necessary to ensure its integrity and quality. we aimed to evaluate the physical, chemical, and microbiological parameters of untreated groundwater drawn from different types of wells, and the antimicrobial suscep ...201627775681
insights into the genome sequences of an n-acyl homoserine lactone molecule producing two pseudomonas spp. isolated from the arctic.we report for the first time the draft genome sequence of two psychrotrophic pseudomonas species, pseudomonas simiae rgcb 73 and pseudomonas brenneri rgcb 108, from the arctic that produce more than one acyl homoserine lactone molecule of varied n-acyl length. the study confirms the presence of a luxr-luxi (type) mediated quorum-sensing system in both the pseudomonas species and enables us to understand the role of quorum sensing in their survival in extremely cold environments.201627491995
highly regio- and enantioselective multiple oxy- and amino-functionalizations of alkenes by modular cascade biocatalysis.new types of asymmetric functionalizations of alkenes are highly desirable for chemical synthesis. here, we develop three novel types of regio- and enantioselective multiple oxy- and amino-functionalizations of terminal alkenes via cascade biocatalysis to produce chiral α-hydroxy acids, 1,2-amino alcohols and α-amino acids, respectively. basic enzyme modules 1-4 are developed to convert alkenes to (s)-1,2-diols, (s)-1,2-diols to (s)-α-hydroxyacids, (s)-1,2-diols to (s)-aminoalcohols and (s)-α-hy ...201627297777
a β-alanine catabolism pathway containing a highly promiscuous ω-transaminase in the 12-aminododecanate-degrading pseudomonas sp. strain aac.we previously isolated the transaminase kes23458 from pseudomonas sp. strain aac as a promising biocatalyst for the production of 12-aminododecanoic acid, a constituent building block of nylon-12. here, we report the subsequent characterization of this transaminase. it exhibits activity with a broad substrate range which includes α-, β-, and ω-amino acids, as well as α,ω-diamines and a number of other industrially relevant compounds. it is therefore a prospective candidate for the biosynthesis o ...201627107110
the net of life: reconstructing the microbial phylogenetic network.it has previously been suggested that the phylogeny of microbial species might be better described as a network containing vertical and horizontal gene transfer (hgt) events. yet, all phylogenetic reconstructions so far have presented microbial trees rather than networks. here, we present a first attempt to reconstruct such an evolutionary network, which we term the "net of life". we use available tree reconstruction methods to infer vertical inheritance, and use an ancestral state inference alg ...200515965028
crystallization and preliminary x-ray diffraction analysis of an anti-h(o) lectin from lotus tetragonolobus seeds.the seed lectin from lotus tetragonolobus (lta) has been crystallized. the best crystals grew over several days and were obtained using the vapour-diffusion method at a constant temperature of 293 k. a complete structural data set was collected at 2.00 angstroms resolution using a synchrotron-radiation source. lta crystals were found to be monoclinic, belonging to space group p2(1), with unit-cell parameters a = 68.89, b = 65.83, c = 102.53 angstroms, alpha = gamma = 90, beta = 92 degrees. molec ...200616820693
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
solution nmr structure of hypothetical protein cv_2116 encoded by a viral prophage element in chromobacterium violaceum.cv_2116 is a small hypothetical protein of 82 amino acids from the gram-negative coccobacillus chromobacterium violaceum. a psi-blast search using the cv_2116 sequence as a query identified only one hit (e = 2e(-07)) corresponding to a hypothetical protein or16_04617 from cupriavidus basilensis or16, which failed to provide insight into the function of cv_2116. the cv_2116 gene was cloned into the p15tvlic expression plasmid, transformed into e. coli, and (13)c- and (15)n-labeled nmr samples of ...201222837698
hmup is a coactivator of irr-dependent expression of heme utilization genes in bradyrhizobium japonicum.utilization of heme as an iron source by bradyrhizobium japonicum involves induction of the outer membrane heme receptor gene hmur and other genes within the heme utilization locus. here, we discovered the hmup gene located upstream of hmur and transcribed divergently from it along with hmutuv. hmup encodes a small protein that accumulated under iron limitation and is transcriptionally controlled by the global iron-responsive regulator irr, as were all genes within the heme utilization locus. cr ...201222505680
quorum quenching enzymes and their application in degrading signal molecules to block quorum sensing-dependent infection.with the emergence of antibiotic-resistant strains of bacteria, the available options for treating bacterial infections have become very limited, and the search for a novel general antibacterial therapy has received much greater attention. quorum quenching can be used to control disease in a quorum sensing system by triggering the pathogenic phenotype. the interference with the quorum sensing system by the quorum quenching enzyme is a potential strategy for replacing traditional antibiotics beca ...201324065091
structural and functional studies of the pseudomonas aeruginosa minor pilin, pile.many bacterial pathogens, including pseudomonas aeruginosa, use type iva pili (t4ap) for attachment and twitching motility. t4ap are composed primarily of major pilin subunits, which are repeatedly assembled and disassembled to mediate function. a group of pilin-like proteins, the minor pilins fimu and pilvwxe, prime pilus assembly and are incorporated into the pilus. we showed previously that minor pilin pile depends on the putative priming subcomplex pilvwx and the non-pilin protein pily1 for ...201526359492
unraveling the contributions of hydrogen-bonding interactions to the activity of native and non-native ligands in the quorum-sensing receptor lasr.quorum sensing (qs) via the synthesis and detection of n-acyl l-homoserine lactone (ahl) signals regulates important pathogenic and mutualistic phenotypes in many bacteria. over the past two decades, the development of non-native molecules that modulate this cell-cell signaling process has become an active area of research. the majority of these compounds were designed to block binding of the native ahl signal to its cognate luxr-type receptor, and much effort has focused on lasr in the opportun ...201525474181
single turnover kinetics of tryptophan hydroxylase: evidence for a new intermediate in the reaction of the aromatic amino acid hydroxylases.tryptophan hydroxylase (trph) uses a non-heme mononuclear iron center to catalyze the tetrahydropterin-dependent hydroxylation of tryptophan to 5-hydroxytryptophan. the reactions of the trph.fe(ii), trph.fe(ii).tryptophan, trph.fe(ii).6meph(4).tryptophan, and trph.fe(ii).6meph(4).phenylalanine complexes with o(2) were monitored by stopped-flow absorbance spectroscopy and rapid quench methods. the second-order rate constant for the oxidation of trph.fe(ii) has a value of 104 m(-1) s(-1) irrespect ...201020687613
macrocyclic histone deacetylase inhibitors.histone deacetylase inhibitors (hdaci) are an emerging class of novel anti-cancer drugs that cause growth arrest, differentiation, and apoptosis of tumor cells. in addition, they have shown promise as anti-parasitic, anti-neurodegenerative, anti-rheumatologic and immunosuppressant agents. to date, several structurally distinct small molecule hdaci have been reported including aryl hydroxamates, benzamides, short-chain fatty acids, electrophilic ketones, and macrocyclic peptides. macrocyclic hdac ...201020536416
identification and characterization of the spiruchostatin biosynthetic gene cluster enable yield improvement by overexpressing a transcriptional activator.spiruchostatins a and b are members of the fk228-family of natural products with potent histone deacetylase inhibitory activities and antineoplastic activities. however, their production in the wild-type strain of pseudomonas sp. q71576 is low. to improve the yield, the spiruchostatin biosynthetic gene cluster (spi) was first identified by rapid genome sequencing and characterized by genetic mutations. this spi gene cluster encodes a hybrid biosynthetic pathway similar to that encoded by the fk2 ...201424973954
bioactivities by a crude extract from the greenlandic pseudomonas sp. in5 involves the nonribosomal peptides, nunamycin and nunapeptin.background. bioactive microbial metabolites provide a successful source of novel compounds with pharmaceutical potentials. the bacterium pseudomonas sp. in5 is a biocontrol strain isolated from a plant disease suppressive soil in greenland, which produces two antimicrobial nonribosomal peptides (nrps), nunapeptin and nunamycin. methods. in this study, we used in vitro antimicrobial and anticancer bioassays to evaluate the potential bioactivities of both a crude extract derived from pseudomonas s ...201526734508
smi2-mediated dimerization of indolylbutenones and synthesis of the myxobacterial natural product indiacen b.the synthesis and reactivity of indole derivatives substituted in the benzene section was studied. starting materials 4- and 6-iodoindole were conveniently prepared via the batcho-leimgruber route and purified by sublimation. novel vicinally indolyl-substituted cyclopentanols with unexpected cis-configuration were formed by smi2-mediated reductive dimerization of a 4-(indol-6-yl)butenone, obtained by heck reaction. the two indolyl units appear to chelate sm(ii)/(iii) leading to a gauche-type arr ...201526664588
chemical methods to interrogate bacterial quorum sensing pathways.bacteria frequently manifest distinct phenotypes as a function of cell density in a phenomenon known as quorum sensing (qs). this intercellular signalling process is mediated by "chemical languages" comprised of low-molecular weight signals, known as autoinducers, and their cognate receptor proteins. as many of the phenotypes regulated by qs can have a significant impact on the success of pathogenic or mutualistic prokaryotic-eukaryotic interactions, there is considerable interest in methods to ...201222948815
acyl-homoserine lactone-dependent eavesdropping promotes competition in a laboratory co-culture model.many proteobacteria use acyl-homoserine lactone (ahl)-mediated quorum sensing to activate the production of antibiotics at high cell density. extracellular factors like antibiotics can be considered public goods shared by individuals within a group. quorum-sensing control of antibiotic production may be important for protecting a niche or competing for limited resources in mixed bacterial communities. to begin to investigate the role of quorum sensing in interspecies competition, we developed a ...201222763647
crystal structure of a putative isochorismatase hydrolase from oleispira antarctica.isochorismatase-like hydrolases (ihl) constitute a large family of enzymes divided into five structural families (by scop). ihls are crucial for siderophore-mediated ferric iron acquisition by cells. knowledge of the structural characteristics of these molecules will enhance the understanding of the molecular basis of iron transport, and perhaps resolve which of the mechanisms previously proposed in the literature is the correct one. we determined the crystal structure of the apo-form of a putat ...201222350524
enhanced synthesis of 5-hydroxy-l-tryptophan through tetrahydropterin regeneration.5-hydroxy-l-tryptophan (5-htp) is a naturally occurring aromatic amino acid present in the seeds of the african plant griffonia simplicifolia. although 5-htp has therapeutic effects in various symptoms, efficient method of producing 5-htp has not been established. in this study, we developed a novel cofactor regeneration process to achieve enhanced synthesis of 5-htp by using modified l-phenylalanine 4-hydroxylase of chromobacterium violaceum. for the synthesis of 5-htp using escherichia coli wh ...201324321061
soil-borne microbial functional structure across different land uses.land use change alters the structure and composition of microbial communities. however, the links between environmental factors and microbial functions are not well understood. here we interrogated the functional structure of soil microbial communities across different land uses. in a multivariate regression tree analysis of soil physicochemical properties and genes detected by functional microarrays, the main factor that explained the different microbial community functional structures was c :  ...201425177716
genome-wide search for eliminylating domains reveals novel function for bles03-like proteins.bacterial phosphothreonine lyases catalyze a novel posttranslational modification involving formation of dehydrobutyrine/dehyroalanine by β elimination of the phosphate group of phosphothreonine or phosphoserine residues in their substrate proteins. though there is experimental evidence for presence of dehydro amino acids in human proteins, no eukaryotic homologs of these lyases have been identified as of today. a comprehensive genome-wide search for identifying phosphothreonine lyase homologs i ...201425062915
pseudomonas cremoricolorata strain nd07 produces n-acyl homoserine lactones as quorum sensing molecules.quorum sensing (qs) is a bacterial cell-to-cell communication system controlling qs-mediated genes which is synchronized with the population density. the regulation of specific gene activity is dependent on the signaling molecules produced, namely n-acyl homoserine lactones (ahls). we report here the identification and characterization of ahls produced by bacterial strain nd07 isolated from a malaysian fresh water sample. molecular identification showed that strain nd07 is clustered closely to p ...201424984061
edwardsiella tarda esce (orf13 protein) is a type iii secretion system-secreted protein that is required for the injection of effectors, secretion of translocators, and pathogenesis in fish.the type iii secretion system (t3ss) of edwardsiella tarda is crucial for its intracellular survival and pathogenesis in fish. the orf13 gene (esce) of e. tarda is located 84 nucleotides (nt) upstream of esrc in the t3ss gene cluster. we found that esce is secreted and translocated in a t3ss-dependent manner and that amino acids 2 to 15 in the n terminus were required for a completely functional t3ss in e. tarda. deletion of esce abolished the secretion of t3ss translocators, as well as the secr ...201526459509
edwardsiella tarda esce (orf13 protein) is a type iii secretion system-secreted protein that is required for the injection of effectors, secretion of translocators, and pathogenesis in fish.the type iii secretion system (t3ss) of edwardsiella tarda is crucial for its intracellular survival and pathogenesis in fish. the orf13 gene (esce) of e. tarda is located 84 nucleotides (nt) upstream of esrc in the t3ss gene cluster. we found that esce is secreted and translocated in a t3ss-dependent manner and that amino acids 2 to 15 in the n terminus were required for a completely functional t3ss in e. tarda. deletion of esce abolished the secretion of t3ss translocators, as well as the secr ...201526459509
potent and selective modulation of the rhlr quorum sensing receptor by using non-native ligands: an emerging target for virulence control in pseudomonas aeruginosa.pseudomonas aeruginosa uses n-acylated l-homoserine lactone signals and a triumvirate of luxr-type receptor proteins--lasr, rhlr, and qscr--for quorum sensing (qs). each of these receptors can contribute to qs activation or repression and, thereby, the control of myriad virulence phenotypes in this pathogen. lasr has traditionally been considered to be at the top of the qs receptor hierarchy in p. aeruginosa; however, recent reports suggest that rhlr plays a more prominent role in infection than ...201526460240
inhibition of nuclear transport of nf-ĸb p65 by the salmonella type iii secretion system effector spvd.salmonella enterica replicates in macrophages through the action of effector proteins translocated across the vacuolar membrane by a type iii secretion system (t3ss). here we show that the spi-2 t3ss effector spvd suppresses proinflammatory immune responses. spvd prevented activation of an nf-ĸb-dependent promoter and caused nuclear accumulation of importin-α, which is required for nuclear import of p65. spvd interacted specifically with the exportin xpo2, which mediates nuclear-cytoplasmic recy ...201627232334
proteomics analysis of the effects of cyanate on chromobacterium violaceum metabolism.chromobacterium violaceum is a gram-negative betaproteobacterium that has been isolated from various brazilian ecosystems. its genome contains the cyn operon, which gives it the ability to metabolize highly toxic cyanate into ammonium and carbon dioxide. we used a proteomics approach to investigate the effects of cyanate on the metabolism of this bacterium. the proteome of cells grown with and without cyanate was compared on 2-d gels. differential spots were digested and identified by mass spect ...201124710289
interference of bacterial cell-to-cell communication: a new concept of antimicrobial chemotherapy breaks antibiotic resistance.bacteria use a cell-to-cell communication activity termed "quorum sensing" to coordinate group behaviors in a cell density dependent manner. quorum sensing influences the expression profile of diverse genes, including antibiotic tolerance and virulence determinants, via specific chemical compounds called "autoinducers". during quorum sensing, gram-negative bacteria typically use an acylated homoserine lactone (ahl) called autoinducer 1. since the first discovery of quorum sensing in a marine bac ...201323720655
structural insight into the mechanism of c-di-gmp hydrolysis by eal domain phosphodiesterases.cyclic diguanylate (or bis-(3'-5') cyclic dimeric guanosine monophosphate; c-di-gmp) is a ubiquitous second messenger that regulates diverse cellular functions, including motility, biofilm formation, cell cycle progression, and virulence in bacteria. in the cell, degradation of c-di-gmp is catalyzed by highly specific eal domain phosphodiesterases whose catalytic mechanism is still unclear. here, we purified 13 eal domain proteins from various organisms and demonstrated that their catalytic acti ...201020691189
structure-based insights into the catalytic power and conformational dexterity of peroxiredoxins.peroxiredoxins (prxs), some of nature's dominant peroxidases, use a conserved cys residue to reduce peroxides. they are highly expressed in organisms from all kingdoms, and in eukaryotes they participate in hydrogen peroxide signaling. seventy-two prx structures have been determined that cover much of the diversity of the family. we review here the current knowledge and show that prxs can be effectively classified by a structural/evolutionary organization into six subfamilies followed by specifi ...201120969484
functional dissection of ssef, a membrane-integral effector protein of intracellular salmonella enterica.during intracellular life, the bacterial pathogen salmonella enterica translocates a complex cocktail of effector proteins by means of the spi2-encoded type iii secretions system. the effectors jointly modify the endosomal system and vesicular transport in host cells. ssef and sseg are two effectors encoded by genes within salmonella pathogenicity island 2 and both effector associate with endosomal membranes and microtubules and are involved in the formation of salmonella-induced filaments. our ...201222529968
re-annotation of protein-coding genes in 10 complete genomes of neisseriaceae family by combining similarity-based and composition-based methods.in this paper, we performed a comprehensive re-annotation of protein-coding genes by a systematic method combining composition- and similarity-based approaches in 10 complete bacterial genomes of the family neisseriaceae. first, 418 hypothetical genes were predicted as non-coding using the composition-based method and 413 were eliminated from the gene list. both the scatter plot and cluster of orthologous groups (cog) fraction analyses supported the result. second, from 20 to 400 hypothetical pr ...201323571676
regulation of organic hydroperoxide stress response by two ohrr homologs in pseudomonas aeruginosa.pseudomonas aeruginosa ohrr and ospr are gene homologs encoding oxidant sensing transcription regulators. ospr is known to regulate gpx, encoding a glutathione peroxidase, while ohrr regulates the expression of ohr that encodes an organic peroxide specific peroxiredoxin. here, we show that ospr mediated gpx expression, like ohrr and ohr, specifically responds to organic hydroperoxides as compared to hydrogen peroxide and superoxide anion. furthermore, the regulation of these two systems is inter ...201627560944
antibacterial activity of extracellular compounds produced by a pseudomonas strain against methicillin-resistant staphylococcus aureus (mrsa) strains.the emergence of multidrug-resistant bacteria is a world health problem. staphylococcus aureus, including methicillin-resistant s. aureus (mrsa) strains, is one of the most important human pathogens associated with hospital and community-acquired infections. the aim of this work was to evaluate the antibacterial activity of a pseudomonas aeruginosa-derived compound against mrsa strains.201323773484
microbial pigments as natural color sources: current trends and future perspectives.synthetic colors have been widely used in various industries including food, textile, cosmetic and pharmaceuticals. however toxicity problems caused by synthetic pigments have triggered intense research in natural colors and dyes. among the natural sources, pigment producing microorganisms hold a promising potential to meet present day challenges. furthermore natural colors not only improve the marketability of the product but also add extra features like anti oxidant, anti cancer properties etc ...201426243889
microbial pigments as natural color sources: current trends and future perspectives.synthetic colors have been widely used in various industries including food, textile, cosmetic and pharmaceuticals. however toxicity problems caused by synthetic pigments have triggered intense research in natural colors and dyes. among the natural sources, pigment producing microorganisms hold a promising potential to meet present day challenges. furthermore natural colors not only improve the marketability of the product but also add extra features like anti oxidant, anti cancer properties etc ...201426243889
evidence for acyl homoserine lactone signal production in bacteria associated with marine sponges.we report for the first time the production of acyl homoserine lactones (ahls) by bacteria associated with marine sponges. given the involvement of ahls in bacterial colonization of many higher organisms, we speculate that such quorum sensing signals could play a part in interactions between sponges and the dense bacterial communities living within them.200415240326
origins of flagellar gene operons and secondary flagellar systems.forty-one flagellated species representing 11 bacterial phyla were used to investigate the origin of secondary flagellar systems and the structure and formation of flagellar gene operons over the course of bacterial evolution. secondary (i.e., lateral) flagellar systems, which are harbored by five of the proteobacterial species considered, originated twice, once in the alphaproteobacterial lineage and again in the common ancestor of the beta- and gammaproteobacteria. the order and organization o ...200717644605
unusual long-chain n-acyl homoserine lactone production by and presence of quorum quenching activity in bacterial isolates from diseased tilapia fish.growth-dependent cell-cell communication termed quorum sensing is a key regulatory system in bacteria for controlling gene expression including virulence factors. in this study five potential bacterial pathogens including bacillus sp. w2.2, klebsiella sp. w4.2, pseudomonas sp. w3 and w3.1 and serratia sp. w2.3 were isolated from diseased tilapia fish in malaysia, supplied by the leading global fish supplier. proteolytic activity assays confirmed that with the exception of klebsiella sp. w4.2, al ...201222952864
cpndb: a chaperonin sequence database.type i chaperonins are molecular chaperones present in virtually all bacteria, some archaea and the plastids and mitochondria of eukaryotes. sequences of cpn60 genes, encoding 60-kda chaperonin protein subunits (cpn60, also known as groel or hsp60), are useful for phylogenetic studies and as targets for detection and identification of organisms. conveniently, a 549-567-bp segment of the cpn60 coding region can be amplified with universal pcr primers. here, we introduce cpndb, a curated collectio ...200415289485
quorum sensing: how bacteria can coordinate activity and synchronize their response to external signals?quorum sensing is used by a large variety of bacteria to regulate gene expression in a cell-density-dependent manner. bacteria can synchronize population behavior using small molecules called autoinducers that are produced by cognate synthases and recognized by specific receptors. quorum sensing plays critical roles in regulating diverse cellular functions in bacteria, including bioluminescence, virulence gene expression, biofilm formation, and antibiotic resistance. the best-studied autoinducer ...201222825856
gut and root microbiota commonalities.animal guts and plant roots have absorption roles for nutrient uptake and converge in harboring large, complex, and dynamic groups of microbes that participate in degradation or modification of nutrients and other substances. gut and root bacteria regulate host gene expression, provide metabolic capabilities, essential nutrients, and protection against pathogens, and seem to share evolutionary trends.201323104406
structural basis for carbapenem-hydrolyzing mechanisms of carbapenemases conferring antibiotic resistance.carbapenems (imipenem, meropenem, biapenem, ertapenem, and doripenem) are β-lactam antimicrobial agents. because carbapenems have the broadest spectra among all β-lactams and are primarily used to treat infections by multi-resistant gram-negative bacteria, the emergence and spread of carbapenemases became a major public health concern. carbapenemases are the most versatile family of β-lactamases that are able to hydrolyze carbapenems and many other β-lactams. according to the dependency of dival ...201525938965
quorum quenching agents: resources for antivirulence therapy.the continuing emergence of antibiotic-resistant pathogens is a concern to human health and highlights the urgent need for the development of alternative therapeutic strategies. quorum sensing (qs) regulates virulence in many bacterial pathogens, and thus, is a promising target for antivirulence therapy which may inhibit virulence instead of cell growth and division. this means that there is little selective pressure for the evolution of resistance. many natural quorum quenching (qq) agents have ...201424886865
quorum sensing and the use of quorum quenchers as natural biocides to inhibit sulfate-reducing bacteria.sulfate-reducing bacteria (srb) are one of the main protagonist groups of biocorrosion in the seawater environment. given their principal role in biocorrosion, it remains a crucial task to develop strategies to reduce the abundance of srbs. conventional approaches include the use of biocides and antibiotics, which can impose health, safety, and environmental concerns. this review examines an alternative approach to this problem. this is achieved by reviewing the role of quorum sensing (qs) in sr ...201627983678
transaminases for the synthesis of enantiopure beta-amino acids.optically pure β-amino acids constitute interesting building blocks for peptidomimetics and a great variety of pharmaceutically important compounds. their efficient synthesis still poses a major challenge. transaminases (also known as aminotransferases) possess a great potential for the synthesis of optically pure β-amino acids. these pyridoxal 5'-dependent enzymes catalyze the transfer of an amino group from a donor substrate to an acceptor, thus enabling the synthesis of a wide variety of chir ...201222293122
identification of a third osmoprotectant transport system, the osmu system, in salmonella enterica.the growth of salmonella enterica serovar typhimurium mutants lacking the prop and prou osmoprotectant transport systems is stimulated by glycine betaine in high-osmolarity media, suggesting that this organism has an additional osmoprotectant transport system. bioinformatic analysis revealed that the genome of this organism contains a hitherto-unidentified operon, designated osmu, consisting of four genes whose products show high similarity to abc-type transport systems for osmoprotectants in ot ...201222609924
quorum sensing activity of mesorhizobium sp. f7 isolated from potable water.we isolated a bacterial isolate (f7) from potable water. the strain was identified as mesorhizobium sp. by 16s rdna gene phylogenetic analysis and screened for n-acyl homoserine lactone (ahl) production by an ahl biosensor. the ahl profile of the isolate was further analyzed using high resolution triple quadrupole liquid chromatography mass spectrometry (lc/ms) which confirmed the production of multiple ahls, namely, n-3-oxo-octanoyl-l-homoserine lactone (3-oxo-c8-hsl) and n-3-oxo-decanoyl-l-hom ...201425177734
proteomic analysis of chromobacterium violaceum and its adaptability to stress.chromobacterium violaceum (c. violaceum) occurs abundantly in a variety of ecosystems, including ecosystems that place the bacterium under stress. this study assessed the adaptability of c. violaceum by submitting it to nutritional and ph stresses and then analyzing protein expression using bi-dimensional electrophoresis (2-de) and maldi mass spectrometry.201526627076
transcriptome analysis revealed that a quorum sensing system regulates the transfer of the pat megaplasmid in agrobacterium tumefaciens.agrobacterium tumefaciens strain p4 is atypical, as the strain is not pathogenic and produces a for this species unusual quorum sensing signal, identified as n-(3-hydroxy-octanoyl)-homoserine lactone (3oh,c8-hsl).201627543103
gqqa, a novel protein in komagataeibacter europaeus involved in bacterial quorum quenching and cellulose formation.we report on the functional screening and identification of an active quorum quenching (qq) gene in the komagataeibacter europaeus strain cect 8546, which is a member of the acetic acid bacteria (aab).201627221658
marine biofilm bacteria evade eukaryotic predation by targeted chemical defense.many plants and animals are defended from predation or herbivory by inhibitory secondary metabolites, which in the marine environment are very common among sessile organisms. among bacteria, where there is the greatest metabolic potential, little is known about chemical defenses against bacterivorous consumers. an emerging hypothesis is that sessile bacterial communities organized as biofilms serve as bacterial refuge from predation. by testing growth and survival of two common bacterivorous nan ...200818648491
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
sensing and reacting to microbes through the inflammasomes.inflammasomes are multiprotein complexes that activate caspase-1, which leads to maturation of the proinflammatory cytokines interleukin 1β (il-1β) and il-18 and the induction of pyroptosis. members of the nod-like receptor (nlr) family, including nlrp1, nlrp3 and nlrc4, and the cytosolic receptor aim2 are critical components of inflammasomes and link microbial and endogenous danger signals to the activation of caspase-1. in response to microbial infection, activation of the inflammasomes contri ...201222430785
structural and thermodynamic insight into phenylalanine hydroxylase from the human pathogen legionella pneumophila.phenylalanine hydroxylase from legionella pneumophila (lppah) has a major functional role in the synthesis of the pigment pyomelanin, which is a potential virulence factor. we present here the crystal structure of lppah, which is a dimeric enzyme that shows high thermostability, with a midpoint denaturation temperature of 79 °c, and low substrate affinity. the structure revealed a dimerization motif that includes ionic interactions and a hydrophobic core, composed of both β-structure and a c-ter ...201324251098
human naip and mouse naip1 recognize bacterial type iii secretion needle protein for inflammasome activation.inflammasome mediated by central nucleotide-binding and oligomerization domain (nod)-like receptor (nlr) protein is critical for defense against bacterial infection. here we show that type iii secretion system (t3ss) needle proteins from several bacterial pathogens, including salmonella typhimurium, enterohemorrhagic escherichia coli, shigella flexneri, and burkholderia spp., can induce robust inflammasome activation in both human monocyte-derived and mouse bone marrow macrophages. needle protei ...201323940371
chromobacterium violaceum: important insights for virulence and biotechnological potential by exoproteomic studies.chromobacterium violaceum is a beta-proteobacterium with high biotechnological potential, found in tropical environments. this bacterium causes opportunistic infections in both humans and animals, that can spread throughout several tissues, quickly leading to the death of the host. genomic studies identified potential mechanisms of pathogenicity but no further studies were done to confirm the expression of these systems. in this study 36 unique protein entries were identified in databank from a ...201323455494
the janthinobacterium sp. hh01 genome encodes a homologue of the v. cholerae cqsa and l. pneumophila lqsa autoinducer synthases.janthinobacteria commonly form biofilms on eukaryotic hosts and are known to synthesize antibacterial and antifungal compounds. janthinobacterium sp. hh01 was recently isolated from an aquatic environment and its genome sequence was established. the genome consists of a single chromosome and reveals a size of 7.10 mb, being the largest janthinobacterial genome so far known. approximately 80% of the 5,980 coding sequences (cdss) present in the hh01 genome could be assigned putative functions. the ...201323405110
the rise of pathogens: predation as a factor driving the evolution of human pathogens in the environment.bacteria in the environment must survive predation from bacteriophage, heterotrophic protists, and predatory bacteria. this selective pressure has resulted in the evolution of a variety of defense mechanisms, which can also function as virulence factors. here we discuss the potential dual function of some of the mechanisms, which protect against heterotrophic protists, and how predation pressure leads to the evolution of pathogenicity. this is in accordance with the coincidental evolution hypoth ...201323354181
molecular keys to the janthinobacterium and duganella spp. interaction with the plant pathogen fusarium graminearum.janthinobacterium and duganella are well-known for their antifungal effects. surprisingly, almost nothing is known on molecular aspects involved in the close bacterium-fungus interaction. to better understand this interaction, we established the genomes of 11 janthinobacterium and duganella isolates in combination with phylogenetic and functional analyses of all publicly available genomes. thereby, we identified a core and pan genome of 1058 and 23,628 genes. all strains encoded secondary metabo ...201627833590
genetic functions of the naip family of inflammasome receptors for bacterial ligands in mice.biochemical studies suggest that the naip family of nlr proteins are cytosolic innate receptors that directly recognize bacterial ligands and trigger nlrc4 inflammasome activation. in this study, we generated naip5(-/-), naip1(-/-), and naip2(-/-) mice and showed that bone marrow macrophages derived from these knockout mice are specifically deficient in detecting bacterial flagellin, the type iii secretion system needle, and the rod protein, respectively. naip1(-/-), naip2(-/-), and naip5(-/-) m ...201627114610
new antiseptic peptides to protect against endotoxin-mediated shock.systemic bacterial infections are associated with high mortality. the access of bacteria or constituents thereof to systemic circulation induces the massive release of immunomodulatory mediators, ultimately causing tissue hypoperfusion and multiple-organ failure despite adequate antibiotic treatment. lipid a, the "endotoxic principle" of bacterial lipopolysaccharide (lps), is one of the major bacterial immunostimuli. here we demonstrate the biological efficacy of rationally designed new syntheti ...201020606063
resistance to quorum-quenching compounds.bacteria have the remarkable ability to communicate as a group in what has become known as quorum sensing (qs), and this trait has been associated with important bacterial phenotypes, such as virulence and biofilm formation. bacteria also have an incredible ability to evolve resistance to all known antimicrobials. hence, although inhibition of qs has been hailed as a means to reduce virulence in a manner that is impervious to bacterial resistance mechanisms, this approach is unlikely to be a pan ...201324014536
the pomegranate: effects on bacteria and viruses that influence human health.pomegranates have been known for hundreds of years for their multiple health benefits, including antimicrobial activity. the recent surge in multidrug-resistant bacteria and the possibility of widespread global virus pandemics necessitate the need for additional preventative and therapeutic options to conventional drugs. research indicates that pomegranates and their extracts may serve as natural alternatives due to their potency against a wide range of bacterial and viral pathogens. nearly ever ...201323762148
enterobacteriaceae in mouth and cloaca of podocnemis expansa and p. unifilis (testudines: chelonia) populations of national park of araguaia plains, brazil.shigella flexnerii and escherichia coli were the most frequent gram-negative bacteria found in the mouth cavity and cloacae of the turtles podocnemis expansa and p. unifilis on beaches in the national park of araguaia, brazil. reptiles are known as salmonella carriers, despite rarely isolated in these turtles.201124031664
human nlrp3 inflammasome senses multiple types of bacterial rnas.inflammasomes are multiprotein platforms that activate caspase-1, which leads to the processing and secretion of the proinflammatory cytokines il-1β and il-18. previous studies demonstrated that bacterial rnas activate the nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3 (nlrp3) inflammasome in both human and murine macrophages. interestingly, only mrna, but neither trna nor rrnas, derived from bacteria could activate the murine nlrp3 inflammasome. here ...201425355909
eradication of pseudomonas aeruginosa biofilms by atmospheric pressure non-thermal plasma.bacteria exist, in most environments, as complex, organised communities of sessile cells embedded within a matrix of self-produced, hydrated extracellular polymeric substances known as biofilms. bacterial biofilms represent a ubiquitous and predominant cause of both chronic infections and infections associated with the use of indwelling medical devices such as catheters and prostheses. such infections typically exhibit significantly enhanced tolerance to antimicrobial, biocidal and immunological ...201222952948
ecthyma gangrenosum in a neonate: not always pseudomonas.ecthyma gangrenosum (eg) is a cutaneous manifestation of invasive infection usually caused by pseudomonas, but can be caused by many bacteria, fungal and viral infections. we present the first reported case of eg caused by invasive escherichia coli in a neonate. a neonate presented with evidence of sepsis and a rapidly evolving 3×3.5 cm(2) well-circumscribed haemorrhagic and necrotic ulcer on the left groin. there was evidence of decreased perfusion of the lower limb owing to pressure effect of ...201323715836
a rare case of ecthyma gangrenosum caused by proteus vulgaris and candida albicans in a patient with castleman disease. 201526618137
stage-specific expression of protease genes in the apicomplexan parasite, eimeria tenella.proteases regulate pathogenesis in apicomplexan parasites but investigations of proteases have been largely confined to the asexual stages of plasmodium falciparum and toxoplasma gondii. thus, little is known about proteases in other apicomplexa, particularly in the sexual stages. we screened the eimeria tenella genome database for proteases, classified these into families and determined their stage specific expression.201223216867
assessing the effectiveness of functional genetic screens for the identification of bioactive metabolites.a common limitation for the identification of novel activities from functional (meta) genomic screens is the low number of active clones detected relative to the number of clones screened. here we demonstrate that constructing libraries with strains known to produce bioactives can greatly enhance the screening efficiency, by increasing the "hit-rate" and unmasking multiple activities from the same bacterial source.201223271424
assessing the effectiveness of functional genetic screens for the identification of bioactive metabolites.a common limitation for the identification of novel activities from functional (meta) genomic screens is the low number of active clones detected relative to the number of clones screened. here we demonstrate that constructing libraries with strains known to produce bioactives can greatly enhance the screening efficiency, by increasing the "hit-rate" and unmasking multiple activities from the same bacterial source.201223271424
plasmid-determined ampc-type beta-lactamases. 200211751104
two structures of a thiazolinyl imine reductase from yersinia enterocolitica provide insight into catalysis and binding to the nonribosomal peptide synthetase module of hmwp1.the thiazolinyl imine reductase from yersinia enterocolitica (irp3) catalyzes the nadph-dependent reduction of a thiazoline ring in an intermediate for the formation of the siderophore yersiniabactin. two structures of irp3 were determined in the apo (1.85 å) and nadp(+)-bound (2.31 å) forms. irp3 is structurally homologous to sugar oxidoreductases such as glucose-fructose oxidoreductase and 1,5-anhydro-d-fructose reductase, as well as to biliverdin reductase. a homology model of the thiazolinyl ...201223066849
improvement of whole-cell transamination with saccharomyces cerevisiae using metabolic engineering and cell pre-adaptation.whole-cell biocatalysis based on metabolically active baker's yeast with engineered transamination activity can be used to generate molecules carrying a chiral amine moiety. a prerequisite is though to express efficient ω-transaminases and to reach sufficient intracellular precursor levels.201728049528
spider mythology across the world. 200111483545
collaborative research networks work.brazil was heralded for completion of the first genome sequence of a plant pathogen following the development of a virtual research center - a collaborative network of laboratories throughout the state of são paulo, drawing on the expertise of a dispersed and diverse scientific community and on investment from both the government and the private sector. strategies key to the success of this model are discussed here in the context of continuing collaborative scientific endeavors in both developed ...200312925684
electron spin relaxation of copper(ii) complexes in glassy solution between 10 and 120 k.the temperature dependence, between 10 and 120 k, of electron spin-lattice relaxation at x-band was analyzed for a series of eight pyrrolate-imine complexes and for ten other copper(ii) complexes with varying ligands and geometry including copper-containing prion octarepeat domain and s100 type proteins. the geometry of the cun4 coordination sphere for pyrrolate-imine complexes with r=h, methyl, n-butyl, diphenylmethyl, benzyl, 2-adamantyl, 1-adamantyl, and tert-butyl has been shown to range fro ...200516343958
electron spin relaxation of copper(ii) complexes in glassy solution between 10 and 120 k.the temperature dependence, between 10 and 120 k, of electron spin-lattice relaxation at x-band was analyzed for a series of eight pyrrolate-imine complexes and for ten other copper(ii) complexes with varying ligands and geometry including copper-containing prion octarepeat domain and s100 type proteins. the geometry of the cun4 coordination sphere for pyrrolate-imine complexes with r=h, methyl, n-butyl, diphenylmethyl, benzyl, 2-adamantyl, 1-adamantyl, and tert-butyl has been shown to range fro ...200516343958
up-regulation of mdr1 and induction of doxorubicin resistance by histone deacetylase inhibitor depsipeptide (fk228) and atra in acute promyelocytic leukemia cells.the multidrug resistance 1 (mdr1) gene product p-glycoprotein (p-gp) is frequently implicated in cross-resistance of tumors to chemotherapeutic drugs. in contrast, acute promyelocytic leukemia (apl) cells do not express mdr1 and are highly sensitive to anthracyclines. the combination of atra and the novel histone deacetylase inhibitor (hdaci) depsipeptide (fk228) induced p-gp expression and prevented growth inhibition and apoptosis in nb4 apl cells subsequently exposed to doxorubicin (dox). atra ...200616223781
histone deacetylase enzymes as potential drug targets in cancer and parasitic diseases.the elucidation of the mechanisms of transcriptional activation and repression in eukaryotic cells has shed light on the important role of acetylation-deacetylation of histones mediated by histone acetyltransferases (hats) and histone deacetylases (hdacs), respectively. another group belonging to the large family of sirtuins (silent information regulators (sirs)) has an (nicotinamide adenine dinucleotide) nad(+)-dependent hdac activity. several inhibitors of hdacs (hdis) have been shown to exert ...200616883049
update on the treatment of cutaneous t-cell lymphoma (ctcl): focus on vorinostat.epigenetic regulation of gene transcription by small molecule inhibitors of histone deacetylases (hdac) is a novel cancer therapy. vorinostat (zolinza()) is the first fda approved hdac-inhibitor for treatment of patients with cutaneous t cell lymphoma (ctcl) who have progressive, persistent or recurrent disease on or following two systemic therapies. vorinostat was active against solid tumors and hematologic malignancies as intravenous and oral preparations in phase i development. in two phase i ...200719707308
rrndb: documenting the number of rrna and trna genes in bacteria and archaea.a dramatic exception to the general pattern of single-copy genes in bacterial and archaeal genomes is the presence of 1-15 copies of each ribosomal rna encoding gene. the original version of the ribosomal rna database (rrndb) cataloged estimates of the number of 16s rrna-encoding genes; the database now includes the number of genes encoding each of the rrnas (5s, 16s and 23s), an internally transcribed spacer region, and the number of trna genes. the rrndb has been used largely by microbiologist ...200818948294
rrndb: documenting the number of rrna and trna genes in bacteria and archaea.a dramatic exception to the general pattern of single-copy genes in bacterial and archaeal genomes is the presence of 1-15 copies of each ribosomal rna encoding gene. the original version of the ribosomal rna database (rrndb) cataloged estimates of the number of 16s rrna-encoding genes; the database now includes the number of genes encoding each of the rrnas (5s, 16s and 23s), an internally transcribed spacer region, and the number of trna genes. the rrndb has been used largely by microbiologist ...200818948294
epigenetic changes in gliomas.epigenetics are defined, in broad-terms, as alterations in gene expression without changes in dna sequence. while histone modifications and dna methylation are two classical means to regulate gene expression, mirna has also recently been documented to govern gene expression in normal as well as cancer cells. in this review, we will first describe briefly histone modifications, dna methylation and mirnas and the functions of these epigenetic marks during different cellular processes involving dna ...200818836290
epigenetic treatment of myelodysplastic syndromes and acute myeloid leukemias.epigenetic mechanisms affecting chromatin structure contribute to regulate gene expression and assure the inheritance of information, which are essential for the proper expression of key regulatory genes in healthy cells, tissues and organs. in the medical field, an increasing body of evidence indicates that altered gene expression or de-regulated gene function lead to disease. cancer cells also suffer a profound change in the genomic methylation patterns and chromatin status. aberrant dna methy ...200818537607
improved total synthesis of the potent hdac inhibitor fk228 (fr-901228).a scaleable synthesis of the potent histone deacetylase (hdac) inhibitor fk228 is described. a reliable strategy for preparing the key beta-hydroxy mercapto heptenoic acid partner was accomplished in nine steps and 13% overall yield. a noyori asymmetric hydrogen-transfer reaction established the hydroxyl stereochemistry in >99:1 er via the reduction of a propargylic ketone.200818205373
novel microarray design strategy to study complex bacterial communities.assessing bacterial flora composition appears to be of increasing importance to fields as diverse as physiology, development, medicine, epidemiology, the environment, and the food industry. we report here the development and validation of an original microarray strategy that allows analysis of the phylogenic composition of complex bacterial mixtures. the microarray contains approximately 9,500 feature elements targeting 16s rrna gene-specific regions. probe design was performed by selecting olig ...200818203854
phase ii multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous t-cell lymphoma.purpose romidepsin (depsipeptide or fk228) is a member of a new class of antineoplastic agents active in t-cell lymphoma, the histone deacetylase inhibitors. on the basis of observed responses in a phase i trial, a phase ii trial of romidepsin in patients with t-cell lymphoma was initiated. patients and methods the initial cohort was limited to patients with cutaneous t-cell lymphoma (ctcl), or subtypes mycosis fungoides or sézary syndrome, who had received no more than two prior cytotoxic regim ...200919826128
romidepsin inhibits ras-dependent growth transformation of nih 3t3 fibroblasts and rie-1 epithelial cells independently of ras signaling inhibition.despite intensive effort, currently no effective anti-ras therapies have successfully reached clinical application. previous studies suggest that the histone deacetylatse (hdac) inhibitor romidepsin, which is currently in clinical trials for the treatment of multiple malignancies, can block ras-dependent signaling and growth transformation. these studies suggest that mutational activation of ras may be a useful biomarker for sensitivity to romidepsin and that the anti-tumor activity of this hdac ...200919682393
selsa, selenium analogs of saha as potent histone deacetylase inhibitors.cancer treatment and therapy has moved from conventional chemotherapeutics to more mechanism-based targeted approach. disturbances in the balance of histone acetyltransferase (hat) and deacetylase (hdac) leads to a change in cell morphology, cell cycle, differentiation, and carcinogenesis. in particular, hdac plays an important role in carcinogenesis and therefore it has been a target for cancer therapy. structurally diverse group of hdac inhibitors are known. the broadest class of hdac inhibito ...200920167479
selsa, selenium analogs of saha as potent histone deacetylase inhibitors.cancer treatment and therapy has moved from conventional chemotherapeutics to more mechanism-based targeted approach. disturbances in the balance of histone acetyltransferase (hat) and deacetylase (hdac) leads to a change in cell morphology, cell cycle, differentiation, and carcinogenesis. in particular, hdac plays an important role in carcinogenesis and therefore it has been a target for cancer therapy. structurally diverse group of hdac inhibitors are known. the broadest class of hdac inhibito ...200920167479
new clinical developments in histone deacetylase inhibitors for epigenetic therapy of cancer.dna methylation and histone acetylation are two well known epigenetic chromatin modifications. epigenetic agents leading to dna hypomethylation and histone hyperacetylation have been approved for treatment of hematological disorders. the first histone deacetylase inhibitor, vorinostat, has been licensed for cutaneous t cell lymphoma treatment. more than 11 new epigenetic agents are in various stages of clinical development for therapy of multiple cancer types. in this review we summarize novel h ...200919486511
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