Irish Times Achilles Heel Probe For Deadly Fungus (Aspergillus Fumigatus)

[Guest guest]

Irish Times Sept 30, 2010 Achilles heel probe for deadly fungus

" ...we are interested in Aspergillus to see if we can find new Achilles

heels that maybe we can use to attack the fungus.â€

To find that chink in the armour, they zoned in on gliotoxin, a molecule

the fungus makes and releases to help it bypass the host’s immune system and

establish an infection.

“What struck us is how could the fungus protect itself against this

molecule, because it’s also a eukaryotic cell like humans,†says Doyle.

“We

couldn’t quite understand how the fungus was able to make it and protect

itself.

â€

Aspergillus also ploughs quite a bit of effort into making the toxin, he

adds. “There are 13 genes involved in making this small molecule. We

thought: why is the fungus investing so much energy and time in making this

molecule? Was the fungus playing a high-risk game, that it was it making this

molecule to enable the infectious process but it could be damaged by it too?â€

_http://www.irishtimes.com/newspaper/sciencetoday/2010/0930/1224279982317.ht

ml_

(http://www.irishtimes.com/newspaper/sciencetoday/2010/0930/1224279982317.html)

Sharon Noonan Kramer

[Guest guest]

Self-Protection against Gliotoxin—A Component of the Gliotoxin Biosynthetic

Cluster, GliT, Completely Protects Aspergillus fumigatus Against Exogenous

Gliotoxin

The pathogenic fungus Aspergillus fumigatus causes disease in immunocompromised

individuals such as cancer patients. The fungus makes a small molecule called

gliotoxin which helps A. fumigatus bypass the immune system in ill people, and

cause disease. Although a small molecule, gliotoxin biosynthesis is enabled by a

complex series of enzymes, one of which is called GliT, in A. fumigatus.

Amazingly, nobody has really considered that gliotoxin might be toxic to A.

fumigatus itself. Here we show that absence of GliT makes A. fumigatus highly

sensitive to added gliotoxin and inhibits fungal growth, both of which can be

reversed by restoring GliT. Neither can the fungus make or release its own

gliotoxin when GliT is missing. We also show that gliotoxin sensitivity can be

totally overcome by adding glutathione, which is an important anti-oxidant

within cells. We demonstrate that gliotoxin addition increases the production of

GliT, and that GliT breaks the disulphide bond in gliotoxin which may be a step

in the pathway for gliotoxin protection or release from A. fumigatus. We

conclude that gliotoxin may mainly be involved in protecting A. fumigatus

against oxidative stress and that it is an accidental toxin.

http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000952

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> Irish Times Sept 30, 2010 Achilles heel probe for deadly fungus

> " ...we are interested in Aspergillus to see if we can find new Achilles

> heels that maybe we can use to attack the fungus.â€

> To find that chink in the armour, they zoned in on gliotoxin, a molecule

> the fungus makes and releases to help it bypass the host’s immune system and

> establish an infection.

> “What struck us is how could the fungus protect itself against this

> molecule, because it’s also a eukaryotic cell like humans,†says Doyle.

“We

> couldn’t quite understand how the fungus was able to make it and protect

itself.

> â€

> Aspergillus also ploughs quite a bit of effort into making the toxin, he

> adds. “There are 13 genes involved in making this small molecule. We

> thought: why is the fungus investing so much energy and time in making this

> molecule? Was the fungus playing a high-risk game, that it was it making this

> molecule to enable the infectious process but it could be damaged by it

too?â€

> _http://www.irishtimes.com/newspaper/sciencetoday/2010/0930/1224279982317.ht

> ml_

>

(http://www.irishtimes.com/newspaper/sciencetoday/2010/0930/1224279982317.html)

>

>

> Sharon Noonan Kramer

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