Re: 2004-full text

[Guest guest]

Did you mean ergot alkaloids?

Latex paint is very common. It gets wet in buildings. This toxic ergot

situation is probably much more common than many people realize, and the

ergot alkaloids are not tested for in mold or mycotoxin tests.

For example, ergots could cause miscarriages. They could cause LSD-like

hallucinations and chronic sleep disturbances. They could cause interruption

of blood flow to extremities.

The mold grows on the surface and I would guess that on some kinds of paint

it may just appear as tiny specks or it may not even be visible to the eye.

This is something scientists SHOULD be studying, because it could be very

important.

I don't know if anybody besides Panaccione and Coyle have written about it.

This is a good example of one typical reason for the huge numbers of

unanswered questions that exist about water damage in buildings and what it

does to people.

On 2/16/08, who <jeaninem660@...> wrote:

>

> abundant respirable ergot alkaloids from the common airborne fungus

> asp.f./also referamce to stachy

> http://aem.asm.org/cgi/content/full/71/6/3106?view=long & pmid=15933008

>

> __

>

[Guest guest]

Its been a while since I read this paper. They actually answered some

of my questions from my last post in the discussion. Its worth

reading.. (scroll down for portions)

On 2/16/08, who <jeaninem660@...> wrote:

>

>

> abundant respirable ergor alkaloids from the common airborne fungus

> asp.f./also referamce to stachy

> http://aem.asm.org/cgi/content/full/71/6/3106?view=long & pmid=15933008

>

>

From APPLIED AND ENVIRONMENTAL MICROBIOLOGY, June 2005, p. 3106–3111

Vol. 71, No. 6

0099-2240/05/$08.000 doi:10.1128/AEM.71.6.3106–3111.2005

Copyright © 2005, American Society for Microbiology. .

Abundant Respirable Ergot Alkaloids from the Common Airborne

Fungus Aspergillus fumigatus†

G. Panaccione* and M. Coyle

quotes:

" DISCUSSION

Our results demonstrate that high levels of certain ergot

alkaloids are associated with conidia of A. fumigatus. The alkaloids

are present in or on conidia produced by cultures

grown on a variety of substrates. Moreover, the conidia of A.

fumigatus are smaller, lighter, and less dense than those of

closely related species. These physical properties may promote

the aerosolization and buoyancy of the conidia, which serve as

vehicles for the alkaloids.

Whether the ergot alkaloids are on the surface of the

conidia, contained within the conidia, or in both locations

cannot be answered definitively with the available data. The

majority of the ergot alkaloids were easily extracted from intact

conidia, which suggests a surface location. A bead-beating

treatment that physically disrupted the spore wall increased

the amount of alkaloid extracted by 38%. However, in addition

to cell breakage, this treatment also more vigorously extracted

any surface compounds. The data from this more disruptive

extraction also indicate that the values in Table 2 represent

minimum values for conidium-associated alkaloids. The question

of the location of the ergot alkaloids relative to the spore

surface may not be significant from a health perspective. In

immunocompetent individuals, inhaled conidia are likely to be

killed and lysed by macrophages (18), releasing any mycotoxins

contained in them. Conidia that are not killed and lysed

present a threat of infection and probably additional toxin

production.

A role for ergot alkaloids in invasive aspergillosis

has not been investigated. Such studies would be facilitated by

comparison of wild-type isolates with the ergot alkaloid-defi-

cient mutants described in the accompanying paper (4). In the

absence of infection, conidia may serve as vehicles for exposure

to ergot alkaloids.

The issue of health risks posed by inhalation of mycotoxin containing

conidia is complex and is affected by several factors,

including the physical nature of the conidia with respect to

their potential for dispersal and inhalation and the production

of mycotoxins on environmentally relevant substrates. The

conidia of A. fumigatus have properties that appear to facilitate

their dispersal and inhalation. The 2.8-m diameter of conidia

is small enough for them to penetrate deep into the alveoli of

the lungs (18). The low specific gravity of the conidia (0.24)

probably promotes efficient air dispersal. For comparison, the

conidia of the trichothecene producer S. chartarum, which

have generated considerable health concerns (10, 28), have a

mass that is 48 times greater and a specific gravity that is four

times greater than those of conidia of A. fumigatus.

Ergot alkaloids were detected on all media tested, including

environmentally relevant substrates such as latex paint, two

different plant materials, and water agar (representative of

moist, nutritionally poor environments). The reported concentrations

of ergot alkaloids associated with conidia produced on

substrates other than PDA were based on the number of

conidia extracted and a value for conidial mass determined

from conidia produced on PDA. Thus, these values were based

on the assumption that conidia produced on any of the alternate

substrates have the same mass as conidia produced on

PDA. We contend that this is a reasonable assumption. However,

if the mass of each conidium were in fact greater on a

natural substrate than on PDA, then the calculated values for

the amount of ergot alkaloid per conidium would be lower.

Conversely, if the conidial mass were lower on a natural substrate

than on PDA, then the alkaloid concentration would be

greater than that shown in Table 2.

A more complicated factor in determination of the health

risks associated with conidial mycotoxins is the issue of

whether the toxins are encountered in quantities sufficient for

them to exert their effects. There are at least three components

to this issue, including (i) the concentration of mycotoxin in

each conidium, (ii) the number of conidia encountered, and

(iii) the toxicity of the mycotoxins.

Concentrations of ergot alkaloids that exceed 1% of the

mass of the A. fumigatus conidia are relatively high for fungal

natural products. There are few data available for direct comparison,

because most mycotoxin data are expressed as mass of

toxin per unit volume of culture. Data for respirable trichothecenes

from S. chartarum (28) revealed a mean of 17 ng of

trichothecenes per mg of dust aerosolized from S. chartarum

cultured on rice. Assuming that conidia, which constituted

85% of the particles in the aerosolized dust (28), contributed

85% of the mass of the dust sample, then 0.002% of the

conidium mass was trichothecenes. Using a different isolate of

the same fungal species and measuring only the most abundant

trichothecene, Nikulin et al. (21) reported 0.1 pg of satratoxin

H per conidium. Based on a mass of 140 pg per conidium

(Table 1), satratoxin H accounted for 0.0007% of the conidial

mass. Another source of alkaloid data based on fungal mass is

the poisonous mushroom literature. For example, in basidiocarps

of Amanita muscaria ibotenic acid accounts for 0.45% of

the dry weight and muscimol accounts for 0.036% (30) (assuming

that 12.5 mg [fresh weight] of basidiocarp yields 1 mg [dry

weight] [9]). Amatoxins have been found to account for 0.1%

to 0.7% of the dry weight of Amanita phalloides basidiocarps

(9). In a more relevant example, ergot sclerotia of field-grown

C. purpurea contain 1% to 2% ergot alkaloids by mass (5, 20).

The number of A. fumigatus conidia available in the air

depends on the substrate and the environment in which the

fungus is growing. Under favorable conditions the fungus can

sporulate prolifically. A typical culture of A. fumigatus on PDA

can yield 109 conidia per cm2 of culture surface area. The

number of viable A. fumigatus conidia per m3 of air ranges

from 0 to 200 CFU in clean environments (27) to 107 CFU

near composting facilities (12) to 1011 CFU near moldy hay or

other stored organic materials (27). If the intake rate was 0.63

m3 of air per h (32), the conidial ergot alkaloid content was 1%

by mass, and there was no further ergot alkaloid production

after inhalation of the fungus, the ergot alkaloid dose would

range from 3.7 pg per h (at 200 CFU/m3) to 180 ng per h (at

107 CFU per m3) to 1.8 mg per h (at 1011 CFU per m3). An

interesting point of reference is that an ingested dose of the

illicit and highly active ergot alkaloid lysergic acid diethylamide

(LSD) can range from hundreds of nanograms to hundreds of

micrograms (1), but based on U.S. Drug Enforcement Agency

data the dose is frequently in the range from 20 to 80 g

(http://www.nida.nih.gov/Infofax/lsd.html). To inhale a comparable

mass of A. fumigatus ergot alkaloids in 1 h would require

exposure to 107 to 1010 CFU per m3. Such high concentrations

of conidia are encountered only rarely. A more practical issue

to consider is whether there are potential health effects of a

less remarkable nature (e.g., effects on depression, blood pressure,

or sleep-wake cycles) that are associated with chronic

daily doses of ergot alkaloids in the nanogram to microgram

range. This issue has not been investigated.

The toxicity of the particular ergot alkaloids associated with

A. fumigatus conidia has not been studied extensively, but the

available data suggest that these mycotoxins have considerable

biological activity. Similar to other ergot alkaloids that have

been studied, festuclavine interacts with receptors for serotonin,

dopamine, and -adrenaline (7, 14, 24, 25). Festuclavine

and synthetic derivatives of festuclavine also are cytostatic in in

vitro assays with several bacteria and mouse lymphoma cell

lines (7, 8). Moreover, festuclavine is unique among the naturally

occurring ergot alkaloids in that it is directly mutagenic in

the Ames test (15). In the only published animal study of

fumigaclavine C, ingestion of relatively crude preparations of

this ergot alkaloid greatly reduced feed intake by treated calves

and caused hemorrhagic enteritis of the small and large intestines,

as well as patchy interstitial thickening of alveolar walls

of the animals (3).

Demonstration of the presence of ergot alkaloids at relatively

high concentrations in or on conidia of A. fumigatus does

not ipso facto indicate that the toxins play a role in pathogenesis,

other health effects, or any specific aspect of the biology of

the fungus. However, it does raise interesting questions for

further research. Studies with ergot alkaloid-deficient mutants,

such as the dmaW knockout strain described in the accompanying

paper (4), should be useful for assessing the contribution

of ergot alkaloids to virulence to animals or potential contributions

of the alkaloids to the ecological success of A. fumigatus.

Since minimization of the mass of a conidium appears to

have been selected for in this fungus, the presence of alkaloids

in quantities that exceed 1% of the mass of the conidium

should have been selected against unless they provided some

advantage to the fungus.

ACKNOWLEDGMENTS

This work was supported by USDA-NRI grant 2001-35319-10930

and Hatch funds.

We thank of the WVU Mass Spectrometry Center for

assistance with mass spectrometry, Barton Baker and Jim Kotcon for

helpful discussions, and and Cipoletti for technical

assistance.

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