Dataset Information

Assessment of oxygen consumption in response to progressive hypoxia.

ABSTRACT: A new method is presented for describing the rate of oxygen consumption in response to progressive hypoxia. The method consists of screening candidate functions describing the relationship between Vo2 (oxygen consumption rate) and Po2 (ambient oxygen concentration) by testing each for fit to observed data for a single curve and the function that best fits is chosen using lowest AICc value as the criterion. Descriptive statistics are then extracted from the selected function that best describes the pattern present in the curve. Several new descriptive statistics for the pattern of response are proposed which are based on the null model of simple diffusion and no regulation. The method quantifies deviation from the null model at each point on the curve and measures both positive and negative deviation which occur when the curve changes more slowly or more rapidly than the null model predicts, respectively. The new descriptive statistics generalize the traditional one used in the past, the critical oxygen tension (Pc), and allow interpretation of a variety of shapes of curves which cannot be analyzed with conventional methods. Because the method is descriptive, it does not implicate any specific mechanisms in generating the response. The method is applied to data from 68 animals in 14 different species groups reported in the literature. The overall results suggest the existence of substantial diversity in response types among animals, which requires a more complex description than has traditionally been used.

SUBMITTER: Cobbs GA

PROVIDER: S-EPMC6303046 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Assessment of oxygen consumption in response to progressive hypoxia.

Cobbs Gary A GA Alexander James E JE

PloS one 20181221 12

A new method is presented for describing the rate of oxygen consumption in response to progressive hypoxia. The method consists of screening candidate functions describing the relationship between Vo2 (oxygen consumption rate) and Po2 (ambient oxygen concentration) by testing each for fit to observed data for a single curve and the function that best fits is chosen using lowest AICc value as the criterion. Descriptive statistics are then extracted from the selected function that best describes t ...[more]

PMID: 30576395

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Project description:Aspergillus fumigatus is a mold responsible for the majority of cases of aspergillosis in humans. To survive in the human body, A. fumigatus must adapt to microenvironments that are often characterized by low nutrient and oxygen availability. Recent research suggests that the ability of A. fumigatus and other pathogenic fungi to adapt to hypoxia contributes to their virulence. However, molecular mechanisms of A. fumigatus hypoxia adaptation are poorly understood. Thus, to better understand how A. fumigatus adapts to hypoxic microenvironments found in vivo during human fungal pathogenesis, the dynamic changes of the fungal transcriptome and proteome in hypoxia were investigated over a period of 24 hours utilizing an oxygen-controlled fermenter system.Significant increases in transcripts associated with iron and sterol metabolism, the cell wall, the GABA shunt, and transcriptional regulators were observed in response to hypoxia. A concomitant reduction in transcripts was observed with ribosome and terpenoid backbone biosynthesis, TCA cycle, amino acid metabolism and RNA degradation. Analysis of changes in transcription factor mRNA abundance shows that hypoxia induces significant positive and negative changes that may be important for regulating the hypoxia response in this pathogenic mold. Growth in hypoxia resulted in changes in the protein levels of several glycolytic enzymes, but these changes were not always reflected by the corresponding transcriptional profiling data. However, a good correlation overall (R(2) = 0.2, p < 0.05) existed between the transcriptomic and proteomics datasets for all time points. The lack of correlation between some transcript levels and their subsequent protein levels suggests another regulatory layer of the hypoxia response in A. fumigatus.Taken together, our data suggest a robust cellular response that is likely regulated both at the transcriptional and post-transcriptional level in response to hypoxia by the human pathogenic mold A. fumigatus. As with other pathogenic fungi, the induction of glycolysis and transcriptional down-regulation of the TCA cycle and oxidative phosphorylation appear to major components of the hypoxia response in this pathogenic mold. In addition, a significant induction of the transcripts involved in ergosterol biosynthesis is consistent with previous observations in the pathogenic yeasts Candida albicans and Cryptococcus neoformans indicating conservation of this response to hypoxia in pathogenic fungi. Because ergosterol biosynthesis enzymes also require iron as a co-factor, the increase in iron uptake transcripts is consistent with an increased need for iron under hypoxia. However, unlike C. albicans and C. neoformans, the GABA shunt appears to play an important role in reducing NADH levels in response to hypoxia in A. fumigatus and it will be intriguing to determine whether this is critical for fungal virulence. Overall, regulatory mechanisms of the A. fumigatus hypoxia response appear to involve both transcriptional and post-transcriptional control of transcript and protein levels and thus provide candidate genes for future analysis of their role in hypoxia adaptation and fungal virulence.

Dataset Information

Assessment of oxygen consumption in response to progressive hypoxia.

Publications

Assessment of oxygen consumption in response to progressive hypoxia.

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