387 research outputs found
Linking species concepts to natural product discovery in the post-genomic era
A widely accepted species concept for bacteria has yet to be established. As a result, species designations are inconsistently applied and tied to what can be considered arbitrary metrics. Increasing access to DNA sequence data and clear evidence that bacterial genomes are dynamic entities that include large numbers of horizontally acquired genes have added a new level of insight to the ongoing species concept debate. Despite uncertainties over how to apply species concepts to bacteria, there is clear evidence that sequence-based approaches can be used to resolve cohesive groups that maintain the properties of species. This cohesion is clearly evidenced in the genus Salinispora, where three species have been discerned despite very close relationships based on 16S rRNA sequence analysis. The major phenotypic differences among the three species are associated with secondary metabolite production, which occurs in species-specific patterns. These patterns are maintained on a global basis and provide evidence that secondary metabolites have important ecological functions. These patterns also suggest that an effective strategy for natural product discovery is to target the cultivation of new Salinispora taxa. Alternatively, bioinformatic analyses of biosynthetic genes provide opportunities to predict secondary metabolite novelty and reduce the redundant isolation of well-known metabolites. Although much remains to be learned about the evolutionary relationships among bacteria and how fundamental units of diversity can be resolved, genus and species descriptions remain the most effective method of scientific communication
Uncovering Genes with Divergent mRNA-Protein Dynamics in Streptomyces coelicolor
Many biological processes are intrinsically dynamic, incurring profound changes at both molecular and physiological levels. Systems analyses of such processes incorporating large-scale transcriptome or proteome profiling can be quite revealing. Although consistency between mRNA and proteins is often implicitly assumed in many studies, examples of divergent trends are frequently observed. Here, we present a comparative transcriptome and proteome analysis of growth and stationary phase adaptation in Streptomyces coelicolor, taking the time-dynamics of process into consideration. These processes are of immense interest in microbiology as they pertain to the physiological transformations eliciting biosynthesis of many naturally occurring therapeutic agents. A shotgun proteomics approach based on mass spectrometric analysis of isobaric stable isotope labeled peptides (iTRAQâą) enabled identification and rapid quantification of approximately 14% of the theoretical proteome of S. coelicolor. Independent principal component analyses of this and DNA microarray-derived transcriptome data revealed that the prominent patterns in both protein and mRNA domains are surprisingly well correlated. Despite this overall correlation, by employing a systematic concordance analysis, we estimated that over 30% of the analyzed genes likely exhibited significantly divergent patterns, of which nearly one-third displayed even opposing trends. Integrating this data with biological information, we discovered that certain groups of functionally related genes exhibit mRNA-protein discordance in a similar fashion. Our observations suggest that differences between mRNA and protein synthesis/degradation mechanisms are prominent in microbes while reaffirming the plausibility of such mechanisms acting in a concerted fashion at a protein complex or sub-pathway level
DETERMINATION OF TYPES OF INDIVIDUALS IN APHIDS, ROTIFERS AND CLADOCERA 1
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72827/1/j.1469-185X.1929.tb00888.x.pd
Polymeric human Fc-fusion proteins with modified effector functions
The success of Fc-fusion bio-therapeutics has spurred the development of other Fc-fusion products for treating and/or vaccinating against a range of diseases. We describe a method to modulate their function by converting them into well-defined stable polymers. This strategy resulted in cylindrical hexameric structures revealed by tapping mode atomic force microscopy (AFM). Polymeric Fc-fusions were significantly less immunogenic than their dimeric or monomeric counterparts, a result partly owing to their reduced ability to interact with critical Fc-receptors. However, in the absence of the fusion partner, polymeric IgG1-Fc molecules were capable of binding selectively to FcÎłRs, with significantly increased affinity owing to their increased valency, suggesting that these reagents may prove of immediate utility in the development of well-defined replacements for intravenous immunoglobulin (IVIG) therapy. Overall, these findings establish an effective IgG Fc-fusion based polymeric platform with which the therapeutic and vaccination applications of Fc-fusion immune-complexes can now be explored
SIGffRid: A tool to search for sigma factor binding sites in bacterial genomes using comparative approach and biologically driven statistics
<p>Abstract</p> <p>Background</p> <p>Many programs have been developed to identify transcription factor binding sites. However, most of them are not able to infer two-word motifs with variable spacer lengths. This case is encountered for RNA polymerase Sigma (<it>Ï</it>) Factor Binding Sites (SFBSs) usually composed of two boxes, called -35 and -10 in reference to the transcription initiation point. Our goal is to design an algorithm detecting SFBS by using combinational and statistical constraints deduced from biological observations.</p> <p>Results</p> <p>We describe a new approach to identify SFBSs by comparing two related bacterial genomes. The method, named SIGffRid (SIGma Factor binding sites Finder using R'MES to select Input Data), performs a simultaneous analysis of pairs of promoter regions of orthologous genes. SIGffRid uses a prior identification of over-represented patterns in whole genomes as selection criteria for potential -35 and -10 boxes. These patterns are then grouped using pairs of short seeds (of which one is possibly gapped), allowing a variable-length spacer between them. Next, the motifs are extended guided by statistical considerations, a feature that ensures a selection of motifs with statistically relevant properties. We applied our method to the pair of related bacterial genomes of <it>Streptomyces coelicolor </it>and <it>Streptomyces avermitilis</it>. Cross-check with the well-defined SFBSs of the SigR regulon in <it>S. coelicolor </it>is detailed, validating the algorithm. SFBSs for HrdB and BldN were also found; and the results suggested some new targets for these <it>Ï </it>factors. In addition, consensus motifs for BldD and new SFBSs binding sites were defined, overlapping previously proposed consensuses. Relevant tests were carried out also on bacteria with moderate GC content (i.e. <it>Escherichia coli</it>/<it>Salmonella typhimurium </it>and <it>Bacillus subtilis</it>/<it>Bacillus licheniformis </it>pairs). Motifs of house-keeping <it>Ï </it>factors were found as well as other SFBSs such as that of SigW in <it>Bacillus </it>strains.</p> <p>Conclusion</p> <p>We demonstrate that our approach combining statistical and biological criteria was successful to predict SFBSs. The method versatility autorizes the recognition of other kinds of two-box regulatory sites.</p
SIGffRid: A tool to search for sigma factor binding sites in bacterial genomes using comparative approach and biologically driven statistics
<p>Abstract</p> <p>Background</p> <p>Many programs have been developed to identify transcription factor binding sites. However, most of them are not able to infer two-word motifs with variable spacer lengths. This case is encountered for RNA polymerase Sigma (<it>Ï</it>) Factor Binding Sites (SFBSs) usually composed of two boxes, called -35 and -10 in reference to the transcription initiation point. Our goal is to design an algorithm detecting SFBS by using combinational and statistical constraints deduced from biological observations.</p> <p>Results</p> <p>We describe a new approach to identify SFBSs by comparing two related bacterial genomes. The method, named SIGffRid (SIGma Factor binding sites Finder using R'MES to select Input Data), performs a simultaneous analysis of pairs of promoter regions of orthologous genes. SIGffRid uses a prior identification of over-represented patterns in whole genomes as selection criteria for potential -35 and -10 boxes. These patterns are then grouped using pairs of short seeds (of which one is possibly gapped), allowing a variable-length spacer between them. Next, the motifs are extended guided by statistical considerations, a feature that ensures a selection of motifs with statistically relevant properties. We applied our method to the pair of related bacterial genomes of <it>Streptomyces coelicolor </it>and <it>Streptomyces avermitilis</it>. Cross-check with the well-defined SFBSs of the SigR regulon in <it>S. coelicolor </it>is detailed, validating the algorithm. SFBSs for HrdB and BldN were also found; and the results suggested some new targets for these <it>Ï </it>factors. In addition, consensus motifs for BldD and new SFBSs binding sites were defined, overlapping previously proposed consensuses. Relevant tests were carried out also on bacteria with moderate GC content (i.e. <it>Escherichia coli</it>/<it>Salmonella typhimurium </it>and <it>Bacillus subtilis</it>/<it>Bacillus licheniformis </it>pairs). Motifs of house-keeping <it>Ï </it>factors were found as well as other SFBSs such as that of SigW in <it>Bacillus </it>strains.</p> <p>Conclusion</p> <p>We demonstrate that our approach combining statistical and biological criteria was successful to predict SFBSs. The method versatility autorizes the recognition of other kinds of two-box regulatory sites.</p
Free-Living Turtles Are a Reservoir for Salmonella but Not for Campylobacter
Different studies have reported the prevalence of Salmonella in turtles and its role in reptile-associated salmonellosis
in humans, but there is a lack of scientific literature related with the epidemiology of Campylobacter in turtles. The
aim of this study was to evaluate the prevalence of Campylobacter and Salmonella in free-living native (Emys
orbicularis, n=83) and exotic (Trachemys scripta elegans, n=117) turtles from 11 natural ponds in Eastern Spain. In
addition, different types of samples (cloacal swabs, intestinal content and water from Turtle containers) were
compared. Regardless of the turtle species, natural ponds where individuals were captured and the type of sample
taken, Campylobacter was not detected. Salmonella was isolated in similar proportions in native (8.0±3.1%) and
exotic (15.0±3.3%) turtles (p=0.189). The prevalence of Salmonella positive turtles was associated with the natural
ponds where animals were captured. Captured turtles from 8 of the 11 natural ponds were positive, ranged between
3.0±3.1% and 60.0±11.0%. Serotyping revealed 8 different serovars among four Salmonella enterica subspecies: S.
enterica subsp. enterica (n = 21), S. enterica subsp. salamae (n = 2), S. enterica subsp. diarizonae (n = 3), and S.
enterica subsp. houtenae (n = 1). Two serovars were predominant: S. Thompson (n=16) and S. typhimurium (n=3).
In addition, there was an effect of sample type on Salmonella detection. The highest isolation of Salmonella was
obtained from intestinal content samples (12.0±3.0%), while lower percentages were found for water from the
containers and cloacal swabs (8.0±2.5% and 3.0±1.5%, respectively). Our results imply that free-living turtles are a
risk factor for Salmonella transmission, but do not seem to be a reservoir for Campylobacter. We therefore rule out
turtles as a risk factor for human campylobacteriosis. Nevertheless, further studies should be undertaken in other
countries to confirm these results.This work was supported by the Conselleria de Infraestructura, Territorio y Medio Ambiente for their assistance and financial support (Life09-Trachemys, Resolution 28/02/12 CITMA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.MarĂn, C.; Ingresa-Capaccioni, S.; GonzĂĄlez BodĂ, S.; Marco JimĂ©nez, F.; Vega Garcia, S. (2013). Free-Living Turtles Are a Reservoir for Salmonella but Not for Campylobacter. PLoS ONE. 8(8):1-6. https://doi.org/10.1371/journal.pone.0072350S1688(2012). The European Union Summary Report on Trends and Sources of Zoonoses, Zoonotic Agents and Foodâborne Outbreaks in 2010. EFSA Journal, 10(3). doi:10.2903/j.efsa.2012.2597Kapperud, G. (2003). Factors Associated with Increased and Decreased Risk of Campylobacter Infection: A Prospective Case-Control Study in Norway. 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(2002). Salmonella Infection Associated With a Pet Lizard in Siblings With Sickle Cell Anemia: An Avoidable Risk. Journal of Pediatric Hematology/Oncology, 24(1), 75-76. doi:10.1097/00043426-200201000-00020Tu, Z.-C., Zeitlin, G., Gagner, J.-P., Keo, T., Hanna, B. A., & Blaser, M. J. (2004). Campylobacter fetus of Reptile Origin as a Human Pathogen. Journal of Clinical Microbiology, 42(9), 4405-4407. doi:10.1128/jcm.42.9.4405-4407.2004Hidalgo-Vila, J., DĂaz-Paniagua, C., PĂ©rez-Santigosa, N., de Frutos-Escobar, C., & Herrero-Herrero, A. (2008). Salmonella in free-living exotic and native turtles and in pet exotic turtles from SW Spain. Research in Veterinary Science, 85(3), 449-452. doi:10.1016/j.rvsc.2008.01.011Harris, J. R., Neil, K. P., Behravesh, C. B., Sotir, M. J., & Angulo, F. J. (2010). Recent Multistate Outbreaks of HumanSalmonellaInfections Acquired from Turtles: A Continuing Public Health Challenge. 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Common variants in P2RY11 are associated with narcolepsy.
Growing evidence supports the hypothesis that narcolepsy with cataplexy is an autoimmune disease. We here report genome-wide association analyses for narcolepsy with replication and fine mapping across three ethnic groups (3,406 individuals of European ancestry, 2,414 Asians and 302 African Americans). We identify a SNP in the 3' untranslated region of P2RY11, the purinergic receptor subtype P2Yââ gene, which is associated with narcolepsy (rs2305795, combined P = 6.1 Ă 10â»Âčâ°, odds ratio = 1.28, 95% CI 1.19-1.39, n = 5689). The disease-associated allele is correlated with reduced expression of P2RY11 in CD8(+) T lymphocytes (339% reduced, P = 0.003) and natural killer (NK) cells (P = 0.031), but not in other peripheral blood mononuclear cell types. The low expression variant is also associated with reduced P2RY11-mediated resistance to ATP-induced cell death in T lymphocytes (P = 0.0007) and natural killer cells (P = 0.001). These results identify P2RY11 as an important regulator of immune-cell survival, with possible implications in narcolepsy and other autoimmune diseases.journal articleresearch support, n.i.h., extramuralresearch support, non-u.s. gov'tresearch support, u.s. gov't, p.h.s.2011 Jan2010 12 19importedErratum in : Nat Genet. 2011 Oct;43(10):1040
Comparison of growth, acetate production, and acetate inhibition of Escherichia coli strains in batch and fed-batch fermentations.
Cloning, purification, and properties of a phosphotyrosine protein phosphatase from Streptomyces coelicolor A3(2).
We describe the isolation and characterization of a gene (ptpA) from Streptomyces coelicolor A3(2) that codes for a protein with a deduced M(r) of 17,690 containing significant amino acid sequence identity with mammalian and prokaryotic small, acidic phosphotyrosine protein phosphatases (PTPases). After expression of S. coelicolor ptpA in Escherichia coli with a pT7-7-based vector system, PtpA was purified to homogeneity as a fusion protein containing five extra amino acids. The purified fusion enzyme catalyzed the removal of phosphate from p-nitrophenylphosphate (PNPP), phosphotyrosine (PY), and a commercial phosphopeptide containing a single phosphotyrosine residue but did not cleave phosphoserine or phosphothreonine. The pH optima for PNPP and PY hydrolysis by PtpA were 6.0 and 6.5, respectively. The Km values for hydrolysis of PNPP and PY by PtpA were 0.75 mM (pH 6.0, 37 degrees C) and 2.7 mM (pH 6.5, 37 degrees C), respectively. Hydrolysis of PNPP by S. coelicolor PtpA were 0.75 mM (pH 6.0, 37 degrees C) and 2.7 mM (pH 6.5, 37 degrees C), respectively. Hydrolysis of PNPP by S. coelicolor PtpA was competitively inhibited by dephostatin with a Ki of 1.64 microM; the known PTPase inhibitors phenylarsine oxide, sodium vanadate, and iodoacetate also inhibited enzyme activity. Apparent homologs of ptpA were detected in other streptomycetes by Southern hybridization; the biological functions of PtpA and its putative homologs in streptomycetes are not yet known
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