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- A. versicolor (1)
- Aspergillus sydowii (1)
- Chad (1)
- Desert sand (1)
- MYCN (1)
- Mass-spectrometry (1)
- Sterigmatocystin (1)
- Tumor metabolism (1)
Organisationseinheit der BAM
Desert dust seeds distant lands and waters
with minerals as well as micro-organisms raising the
question of whether this ancient phenomenon also
spreads pathogens across the globe. Severe dust
storms require strong winds blowing over land-masses
that are largely devoid of vegetation, effectively
limiting the scope for winds to raise pathogens into
the air. Nevertheless, changing patterns of land-use,
often driven by belligerency, result in refugees
spreading to areas that were previously deemed barely
habitable. With the help of the International Committee
of the Red Cross, a number of sand/dust samples
were collected from the Republic of Chad, some near
refugee camps, others further removed from human
influence. In parallel studies, we documented the
micro-organisms present in these samples and used a
number of the isolates here to test the effect of
environmental constraints on their ability to survive
intercontinental flight. We also added traditional
pathogens to the palette of microbes and tested the
effects of UV irradiation, desiccation and temperature
on survival of both bacteria and fungi. A clear trend
was obvious—those microbes that are coloured or able
to form conidia or spores (in other words, those that
are native to deserts) were well able to resist the
imposed stresses. On the other hand, most pathogens
were more sensitive to stresses than the environmental
isolates. Toxin production in two species of Aspergillus
was also investigated. Short-term desiccation
(simulating environmental conditions during intercontinental
travel) of sand amended with fungal spores
containing sterigmatocystin leads to increased mycotoxin
contents, but significant mycotoxin production
was only possible under growth-permissive conditions,
e.g. at higher humidity. It thus seems likely that an ever-decreasing fraction of the initial pathogen load
survives as the dust recedes from its desert source and
that those organisms that land on other continents are
highly enriched in desert dwellers.
MYCN is a transcription factor that is aberrantly expressed in many tumor types and is often correlated with poor patient prognosis. Recently, several lines of evidence pointed to the fact that oncogenic activation of MYC family proteins is concomitant with reprogramming of tumor cells to cope with an enhanced need for metabolites during cell growth. These adaptions are driven by the ability of MYC proteins to act as transcriptional amplifiers in a tissue-of-origin specific manner. Here, we describe the effects of MYCN overexpression on metabolic reprogramming in neuroblastoma cells. Ectopic expression of MYCN induced a glycolytic switch that was concomitant with enhanced sensitivity towards 2-deoxyglucose, an inhibitor of glycolysis. Moreover, global metabolic profiling revealed extensive alterations in the cellular metabolome resulting from overexpression of MYCN. Limited supply with either of the two main carbon sources, glucose or glutamine, resulted in distinct shifts in steady-state metabolite levels and significant changes in glutathione metabolism. Interestingly, interference with glutamine-glutamate conversion preferentially blocked proliferation of MYCN overexpressing cells, when glutamine levels were reduced. Thus, our study uncovered MYCN induction and nutrient levels as important metabolic master switches in neuroblastoma cells and identified critical nodes that restrict tumor cell proliferation.