Breaking the mold: Research teams sequence three fungus genomes

From garden compost to forest greenery, the mold Aspergillus fumigatus lurks across much of the world. And so does its impact. The most common mold causing infection, A. fumigatus triggers allergic reactions, asthma attacks–and even deadly infections among people with weakened immune systems.

Now, in the December 22 issue of the journal Nature, scientists at The Institute for Genomic Research (TIGR) and their collaborators report the mold’s sequenced genome. The genome could lead researchers to A. fumigatus genes with the potential to generate better diagnostics and treatment for fungal infection. “This genome sequence is going to be central for developing tools for effectively managing A. fumigatus infections as they become more prevalent in the aging population,” predicts first author William Nierman, a microbiologist at TIGR.

Nierman co-authored two additional Aspergillus genome papers in the same issue of Nature. One describes a genome project on Aspergillus oryzae, a nonpathogenic food industry workhorse that has produced sake (rice wine), miso (soybean paste), and shoyu (soy sauce) for 2,000 years. The third paper reports the genome sequence of model organism Aspergillus nidulans and compares the organism to A. oryzae and A. fumigatus. The work was carried out collaboratively at several institutions in the U.S., U.K., Spain, Japan, France, Brazil, Austria, Switzerland, and Germany. David Denning of the University of Manchester coordinated the projects.

Unlike most fungi, A. fumigatus likes it hot–and hotter. The fungus enjoys an unusual range of temperatures. At home in the compost heap, A. fumigatus tolerates temperatures up to 70 degrees Celsius. The fungus becomes a human pathogen because it’s perfectly comfortable at body temperature, 37 degrees C. Altering ambient temperatures in the lab, TIGR scientists tracked gene activity, documenting different A. fumigatus genes that turned on and off, as the environment warmed.

The A. fumigatus genome is 28 Mb in size, consisting of 8 chromosomes bearing a total of almost 10,000 genes. Which genes make the mold virulent? Some 700 A. fumigatus genes significantly differ–or do not even occur–in a similar, yet less infectious fungus, Neosartorya fischeri. Nierman and colleagues are now searching these unique genes for clues to A. fumigatus infectivity.

It’s a complex task. Suspect genes encode proteins involved in central metabolic pathways, cell signaling, cell wall biosynthesis, pigment biosynthesis, and secondary metabolite production. In other words, A. fumigatus’s virulence genes are likely complex and mixed up with normal metabolic capabilities, Nierman says. He and his colleagues now plan to systematically “knock out,” or disable, genes that might make A. fumigatus infectious. Eventually, Nierman adds, this work could lead to better therapies for serious asthma, allergy, and other conditions.