Dataset Information

The responses of the pulmonary pathogen Aspergillus fumigatus to the neutrophil derived oxidant N- chlorotaurine

ABSTRACT: Aspergillus fumigatus is a pulmonary pathogen to individuals who are immunocompromised (e.g. mylosuppression) and those who display defects in immune equilibrium, commonly observed in the Cystic fibrosis lung and presents itself in the form as allergic bronchopulmonary aspergillosis.32 In the latter disease A. fumigatus airborne conidia penetrate the lower airways, germinate and and grow within in thick tenacious CF mucus. A. fumigatus CF colonized individuals can become sensitized to A. fumigatus secreted allergens and eventually develop a type 2 hypersensitivity reaction to AF allergens, toxins and proteases which are readily replenished into the mucus which can directly cause cell damage and peeling at the bronco – epithelium interface. A. fumigatus also induces invasive disease which carries up to 90% mortality. The effect of neutrophil oxidant NCT on A. fumigatus was determined as neutrophils are the first line of cellular defense against A. fumigatus.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Aspergillus Fumigatus Var. Fumigatus

SUBMITTER: Gerard Sheehan

LAB HEAD: Prof. Kevin Kavanagh

PROVIDER: PXD009853 | Pride | 2018-12-19

REPOSITORIES: Pride

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Publications

Reduced TCA cycle rates at high hydrostatic pressure hinder hydrocarbon degradation and obligate oil degraders in natural, deep-sea microbial communities.

Scoma Alberto A Heyer Robert R Rifai Ridwan R Dandyk Christian C Marshall Ian I Kerckhof Frederiek-Maarten FM Marietou Angeliki A Boshker Henricus T S HTS Meysman Filip J R FJR Malmos Kirsten G KG Vosegaard Thomas T Vermeir Pieter P Banat Ibrahim M IM Benndorf Dirk D Boon Nico N

The ISME journal 20181212 4

Petroleum hydrocarbons reach the deep-sea following natural and anthropogenic factors. The process by which they enter deep-sea microbial food webs and impact the biogeochemical cycling of carbon and other elements is unclear. Hydrostatic pressure (HP) is a distinctive parameter of the deep sea, although rarely investigated. Whether HP alone affects the assembly and activity of oil-degrading communities remains to be resolved. Here we have demonstrated that hydrocarbon degradation in deep-sea mi ...[more]

PMID: 30542078

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Project description:Background: Cystic fibrosis (CF) is caused by mutations in the CFTR gene that impair function of this cAMP-regulated Cl- channel. In the small intestine, loss of CFTR function creates a dehydrated, acidic luminal environment which is believed to cause an accumulation of mucus, a phenotype characteristic of CF. CF mice have an innate immune response and impaired intestinal transit as well. We investigated whether lubiprostone, which activates the CLC2 Cl- channel, would improve the CF intestinal phenotype. Methods: Cftrtm1UNC (CF) and wildtype (WT) littermate mice on the C57BL/6 background were used. Lubiprostone (10ug/kg-day) was administered by gavage for two weeks. Mucus accumulation was estimated from crypt lumen widths in Carnoy's-fixed, PAS/AB stained sections. Luminal bacterial load was measured by qPCR for the bacterial 16S gene. Gastric emptying and small intestinal transit were assessed by gavage of rhodamine dextran. Gene expression was evaluated by Affymetrix Mouse430 2.0 microarray. Results: Crypt width in control CF mice was 700% that of WT mice (P<0.001). Lubiprostone did not affect WT crypt width but, unexpectedly, increased CF crypt width 22% (P=0.001). Lubiprostone increased bacterial load in WT mice to 490% of WT control levels (P=0.008). Conversely, lubiprostone decreased bacterial overgrowth in CF mice by 60% (P=0.005). Lubiprostone significantly increased gastric emptying at 20 min postgavage in both WT (P<0.001; control=57±3%, treated=81±4%) and CF mice (P<0.001; control=48±4%, treated=75±5%). After lubiprostone small intestinal transit was significantly enhanced in WT mice (P=0.024) but the effect was not significant in CF mice (P=0.377). Among other innate immune markers, expression of mast cell genes was elevated ~20-fold in the control CF intestine and lubiprostone decreased expression to WT control levels. Conclusions: These results indicate that lubiprostone has some benefits for the CF intestinal phenotype, especially on bacterial overgrowth and the innate immune response. The unexpected observation of increased mucus accumulation in the crypts of lubiprostone-treated CF mice suggests the possibility that lubiprostone increases mucus secretion. For each group (control wild type, lubiprostone-treated wild type, contol Cftr null, and lubiprostone-treated cftr null), equal amounts of total RNA extracted from the entire small intestine were pooled for analysis.

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Dataset Information

The responses of the pulmonary pathogen Aspergillus fumigatus to the neutrophil derived oxidant N- chlorotaurine

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Publications

Reduced TCA cycle rates at high hydrostatic pressure hinder hydrocarbon degradation and obligate oil degraders in natural, deep-sea microbial communities.

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