Regulation of SpeB in Streptococcus pyogenes by pH and NaCl: a model for in vivo gene expression

For a pathogen such as Streptococcus pyogenes, ecological success is determined by its ability to sense the environment and mount an appropriate adaptive transcriptional response. Thus, determining conditions for analyses of gene expression in vitro that are representative of the in vivo environment is critical for understanding the contributions of transcriptional response pathways to pathogenesis. In this study, we determined that the gene encoding the SpeB cysteine protease is up-regulated over the course of infection in a murine soft-tissue model. Conditions were identified, including growth phase, acidic pH, and an NaCl concentration of <0.1 M, that were required for expression of speB in vitro. Analysis of global expression profiles in response to these conditions in vitro identified a set of coregulated genes whose expression patterns showed a significant correlation with that of speB when examined during infection of murine soft tissues. This analysis revealed that a culture medium that promotes high levels of SpeB expression in vitro produced an expression profile that showed significant correlation to the profile observed in vivo. Taken together, these studies establish culture conditions that mimic in vivo expression patterns; that growth phase, pH, and NaCl may mimic relevant cues sensed by S. pyogenes during infection; and that identification of other environmental cues that alter expression of speB in vitro may provide insight into the signals that direct global patterns of gene expression in vivo

Quantifying loss of yield potential due to leaf disease.

To determine the impact of Septoria and barley yellow dwarf virus on wheat grown under the package approach on the south coast using different levels of fungicide and insecticide control on a susceptible variety of an appropriate maturity for early sowing. Examine if there is any benefit for disease control of S. tritici from Baytan seed dressing. 92AL16. Time of sowing and variety effects on the Septoria diseases of wheat. 92AL17. Time of sowing effect on barley foliar diseases. 92AL19. Evaluating variety mixtures to reduce Septoria using a range of lines. 92AL24. Fungicides for control of Septoria nodorum of wheat. 92BA19. Evaluating variety mixtures to reduce Septoria using a range of lines. 92BA20. Effects of Septoria avenae blotch on oat lines and cultivars varying in resistance, maturity and height. 92BA21. Fungicide control of leaf disease in early sown spear wheat. 92ES44 Effects of straw inoculum on leaf disease of wheat. 92BA52. Fungicide control of leaf disease in early sown spear wheat. 92ES44. Rates and timing of fungicides for control of leaf rust and Septoria. 92ES48. To evaluate a range of fungicides for control of leaf rust and other leaf diseases. 92GE90. To evaluate different rates and spray volumes of fungicide for control of leaf rust and Septoria. 92LG62. To evaluate different rates of fungicides for control of leaf rust and other Septoria. 92LG63. Evaluating variety mixtures to reduce Septoria using a range of lines. 92MT34. Effects of Septoria avenae blotch on oat lines and cultivars varying in resistance, maturity and height. 92MT35. Inoculum potential of 18 month old wheat stubbles. 92PE24.\ Response of elite breeding lines to Septoria nodorum. 92PE31. Fungicide control of leaf rust in Corrigin wheat. 92NA79. Fungicide control of wheat leaf rust. 92NO82. Effects of fungicide application on leaf rust and other diseases. 92NO99. Effect of fungicide on wheat leaf rust and Septoria in early sown dagger wheat. 92NO101. Rates and timing of tilt for control of leaf rust and Septoria in early sown spear. 92TS42. Rates and timing of tilt for control of leaf rust in late sown kulin. 92TS43

Foliar wheat diseases and cereal smuts.

Chemical control of leaf spots of wheat, 86BA41, 86MT49. Semi-natural inoculum for plant breeders plots, 86MD2. Chemical control of soil-borne flag smut, 86ME73, 86M032. Chemical control of barley loose smut, 86AL50, 86KA59, 86MT47. Chemical control of loose smut in barley with different levels of seed infections, 86MT48. Disease characterisation of cereal variety trial stage 4 sites

Ybcl of uropathogenic escherichia coli suppresses transepithelial neutrophil migration

Uropathogenic Escherichia coli (UPEC) strains suppress the acute inflammatory response in the urinary tract to ensure access to the intracellular uroepithelial niche that supports the propagation of infection. Our understanding of this initial cross talk between host and pathogen is incomplete. Here we report the identification of a previously uncharacterized periplasmic protein, YbcL, encoded by UPEC that contributes to immune modulation in the urinary tract by suppressing acute neutrophil migration. In contrast to wild-type UPEC, an isogenic strain lacking ybcL expression (UTI89 ΔybcL) failed to suppress transepithelial polymorphonuclear leukocyte (PMN) migration in vitro, a defect complemented by expressing ybcL episomally. YbcL homologs are present in many E. coli genomes; expression of the YbcL variant encoded by nonpathogenic E. coli K-12 strain MG1655 (YbcL(MG)) failed to complement the UTI89 ΔybcL defect, whereas expression of the UPEC YbcL variant (YbcL(UTI)) in MG1655 conferred the capacity for suppressing PMN migration. This phenotypic difference was due to a single amino acid difference (V78T) between the two YbcL homologs, and a majority of clinical UPEC strains examined were found to encode the suppressive YbcL variant. Purified YbcL(UTI) protein suppressed PMN migration in response to live or killed MG1655, and YbcL(UTI) was detected in the supernatant during UPEC infection of bladder epithelial cells or PMNs. Lastly, early PMN influx to murine bladder tissue was augmented upon in vivo infection with UTI89 ΔybcL compared with wild-type UPEC. Our findings demonstrate a role for UPEC YbcL in suppression of the innate immune response during urinary tract infection

Local generation of kynurenines mediates inhibition of neutrophil chemotaxis by uropathogenic Escherichia coli

During epithelial infections, pathogenic bacteria employ an array of strategies to attenuate and evade host immune responses, including the influx of polymorphonuclear leukocytes (PMN; neutrophils). Among the most common bacterial infections in humans are those of the urinary tract, caused chiefly by uropathogenic Escherichia coli (UPEC). During the establishment of bacterial cystitis, UPEC suppresses innate responses via multiple independent strategies. We recently described UPEC attenuation of PMN trafficking to the urinary bladder through pathogen-specific local induction of indoleamine 2,3-dioxygenase (IDO), a tryptophan catabolic enzyme previously shown to have regulatory activity only in adaptive immunity. Here, we investigated the mechanism by which IDO induction attenuates PMN migration. Local tryptophan limitation, by which IDO is known to influence T cell longevity and proliferation, was not involved in its effect on PMN trafficking. Instead, metabolites in the IDO pathway, particularly l-kynurenine, directly suppressed PMN transepithelial migration and induced an attached, spread morphology in PMN both at rest and in the presence of chemotactic stimuli. Finally, kynurenines represent known ligands of the mammalian aryl hydrocarbon receptor (AHR), and UPEC infection of Ahr(−/−) mice recapitulated the derepressed PMN recruitment observed previously in Ido1(−/−) mice. UPEC therefore suppresses neutrophil migration early in bacterial cystitis by eliciting an IDO-mediated increase in local production of kynurenines, which act through the AHR to impair neutrophil chemotaxis

Novel Myopia Genes and Pathways Identified From Syndromic Forms of Myopia

PURPOSE. To test the hypothesis that genes known to cause clinical syndromes featuring myopia also harbor polymorphisms contributing to nonsyndromic refractive errors. METHODS. Clinical phenotypes and syndromes that have refractive errors as a recognized feature were identified using the Online Mendelian Inheritance in Man (OMIM) database. One hundred fifty-four unique causative genes were identified, of which 119 were specifically linked with myopia and 114 represented syndromic myopia (i.e., myopia and at least one other clinical feature). Myopia was the only refractive error listed for 98 genes and hyperopia and the only refractive error noted for 28 genes, with the remaining 28 genes linked to phenotypes with multiple forms of refractive error. Pathway analysis was carried out to find biological processes overrepresented within these sets of genes. Genetic variants located within 50 kb of the 119 myopia-related genes were evaluated for involvement in refractive error by analysis of summary statistics from genome-wide association studies (GWAS) conducted by the CREAM Consortium and 23andMe, using both single-marker and gene-based tests. RESULTS. Pathway analysis identified several biological processes already implicated in refractive error development through prior GWAS analyses and animal studies, including extracellular matrix remodeling, focal adhesion, and axon guidance, supporting the research hypothesis. Novel pathways also implicated in myopia development included mannosylation, glycosylation, lens development, gliogenesis, and Schwann cell differentiation. Hyperopia was found to be linked to a different pattern of biological processes, mostly related to organogenesis. Comparison with GWAS findings further confirmed that syndromic myopia genes were enriched for genetic variants that influence refractive errors in the general population. Gene-based analyses implicated 21 novel candidate myopia genes (ADAMTS18, ADAMTS2, ADAMTSL4, AGK, ALDH18A1, ASXL1, COL4A1, COL9A2, ERBB3, FBN1, GJA1, GNPTG, IFIH1, KIF11, LTBP2, OCA2, POLR3B, POMT1, PTPN11, TFAP2A, ZNF469). CONCLUSIONS. Common genetic variants within or nearby genes that cause syndromic myopia are enriched for variants that cause nonsyndromic, common myopia. Analysis of syndromic forms of refractive errors can provide new insights into the etiology of myopia and additional potential targets for therapeutic interventions

Novel Myopia Genes and Pathways Identified From Syndromic Forms of Myopia

P URPOSE . To test the hypothesis that genes known to cause clinical syndromes featuring myopia also harbor polymorphisms contributing to nonsyndromic refractive errors

Novel Myopia Genes and Pathways Identified From Syndromic Forms of Myopia

Clinical phenotypes and syndromes that have refractive errors as a recognized feature were identified using the Online Mendelian Inheritance in Man (OMIM) database. One hundred fifty-four unique causative genes were identified, of which 119 were specifically linked with myopia and 114 represented syndromic myopia (i.e., myopia and at least one other clinical feature). Myopia was the only refractive error listed for 98 genes and hyperopia and the only refractive error noted for 28 genes, with the remaining 28 genes linked to phenotypes with multiple forms of refractive error. Pathway analysis was carried out to find biological processes overrepresented within these sets of genes. Genetic variants located within 50 kb of the 119 myopia-related genes were evaluated for involvement in refractive error by analysis of summary statistics from genome-wide association studies (GWAS) conducted by the CREAM Consortium and 23andMe, using both single-marker and gene-based tests

Novel Myopia Genes and Pathways Identified From Syndromic Forms of Myopia

Clinical phenotypes and syndromes that have refractive errors as a recognized feature were identified using the Online Mendelian Inheritance in Man (OMIM) database. One hundred fifty-four unique causative genes were identified, of which 119 were specifically linked with myopia and 114 represented syndromic myopia (i.e., myopia and at least one other clinical feature). Myopia was the only refractive error listed for 98 genes and hyperopia and the only refractive error noted for 28 genes, with the remaining 28 genes linked to phenotypes with multiple forms of refractive error. Pathway analysis was carried out to find biological processes overrepresented within these sets of genes. Genetic variants located within 50 kb of the 119 myopia-related genes were evaluated for involvement in refractive error by analysis of summary statistics from genome-wide association studies (GWAS) conducted by the CREAM Consortium and 23andMe, using both single-marker and gene-based tests