Mould growth on building materials - Statens Byggeforskningsinstitut

late produced satratoxins and high quantities of stachybotrylacetones and the later strain
produced only minor quantities of the latter type. The same group 216 also instilled mice with
10 3 and 10 5 spores of the same two S. chartarum isolates 6 times during 3 weeks. In the
mice instilled with the highest dose, severe inflammatory changes were observed in the
lungs. The mice administered with spores from #72 developed much more severe inflammations
than the mice instilled with spores from #29. At the lowest level only the mice instilled
with the spores from the satratoxin producing isolate, #72, developed inflammatory changes
in the lungs. However due to the few isolates used and the variation in both MTR and
stachybotrylacetone production the study remains partly inconclusive on the responsible
components.
This is the same for the study of Mason et al 217,218 who instilled S. chartarum spores and isosatratoxin
F in the lungs of mice, and observed that both obstructed the lung homeostasis
whereas Cladosporium spores did not. However the S. chartarum spores and the pure toxin
induced very different surfactant production (P60 and P100 phosphor lipids), but no chemical
analyses were performed on the strain so it is unknown if it produced MTR.
Rao et al 219 instilled spores in rat lungs, and showed that when spores from a highly cytotoxic
(presumably a MTR producer) of S. chartarum was methanol extracted, the toxicity of the
spores almost disappeared compared with unextracted spores. This clearly shows that the
pulmonary toxicity is due to extractable metabolites as MTR or most of the metabolites described
in the following subchapter.
The conclusion drawn from these studies is that S. chartarum spores indeed contains a
number of metabolites which can induce severe inflammation, haemorrhage and death in
animals. However there is no evidence that these effects are only caused by the MTR.
2.4.1.2 Non trichothecene metabolites
Most species in Stachybotrys and especially S. chartarum produces high quantities of a
number of spiriocyclic drimanes 183,220 as
shown in Figure 3. These components
have a number of biological properties,
inter alia inhibition of TNFα liberation
from human macrophages 221 , complement
inhibition 183,222 and antiviral activity
223 . When considering that one of the
most common symptoms in mouldy
buildings is recurrent airway infections,
HO
HO
metabolites which inhibits the complement system are interesting, as the complemet system
is an important part of our defence against bacteria 143 . A number of triprenyl phenol metabolites
(see Figure 3) have been described from several Stachybotrys species. They are precursors
of the spiriocyclic drimanes, as the triprenyl can be cyclizied into the drimane part.
These metabolites can activate and enhance the plasminogen-mediated fibrinolysis (at levels
down to 100 µM) 224-226 and could in that way be plausible components responsible for IPH,
as this could account for the brittle blood vessels in the lungs.
Both the triprenyl phenols and the spiriocyclic drimanes are produced by two mixed biosynthetic
pathways, partly by the sesquiterpenoid pathway (shown in blue on Figure 3) and
partly by the polyketide pathway. Reviewing the literature on these components has been
troublesome as Russian groups have published known structures under new names, data on
the stereochemistry is often not available, and a significant number of the publications have
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O
O
X
Figure 3. Left, the spiriocyclic drimanes, stachybotrylactone
(X=O) and stachybotrylactam (X=NH). Right, SMTP-1, one of
their precursors.
HO
O
OH
N
O
OH