Aspergillus fumigatus

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A Microbial Biorealm page on the genus Aspergillus fumigatus

Contents

Classification

Higher order taxa

Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes; Eurotiomycetidae; Eurotiales; Trichocomaceae; mitosporic Trichocomaceae; Aspergillus

Species

NCBI: Taxonomy

Aspergillus Fumigatus

Description and significance

Aspergillus fumigatus is a filamentous fungus that can be found worldwide. It is considered an airborne saprophytic fungi. Because of this, it naturally lives in the soil and is a common mould found among compost and plant surfaces. Here it plays a key role in recycling the carbon and nitrogen from deceased organisms. Its conidia can be taken up with the wind and float through the air. It is estimated that there are approximately ten conidia found within every cubic meter of air (2).

Aspergillus fumigatus is also considered to be an opportunistic pathogen to immunocompromised individuals (1). Within recent years, this has become a point of interest as more medical strategies have involved the use of immunosuppressive therapies. This has lead to an increase in Aspergillus fumigates related illnesses, also known as Aspergillosis (1). The fungi gains access to an individual through the respiratory tract and can lead to various allergies and diseases of varying severity up to and including death. When infected, mortality rates are estimated up to 50% (1). Currently treatments consist of antifungal medications and remain relatively ineffective (8). Sequencing of the fungus was completed in 2005 with the use of the clinically isolated strain Af293 (8). With this, attention has been moved in understanding the life cycle and metabolic systems present in the species in order to develop a successful form of treatment.

Genome structure

The isolated strain of Af293 was found to consist of a haploid 29.4-megabase genome. The sequence consists of eight chromosomes consisting of 9,926 genes (8). Found within the genome were sets of temperature dependent gene sets that allow it to survive in varying temperatures up to 70 C, temperatures characteristic of compost piles. At varying temperatures, including those found in the human body and topical soil, there has shown to be different gene expression patterns with comparable numbers of genes being differentially expressed (3).

Also found within the genome were genes previously known for being involved in sexual reproduction, hinting at a recent evolutionary history of sexual reproduction in a fungus previously thought to reproduce asexually (5). Evidence for sexual reproduction was found in the two mating types Mat-2 and Mat-1, each showing expression during mycelial growth at the RNA level of α pheromone precursors and receptors (2). Precursors were found to have a higher expression within Mat-1 (5). The fungi’s source of virulence is found within 26 clusters, all consisting of polyketide synthase and non-ribosomal peptide synthase genes. These clusters encode the secondary metabolites that aid in virulence (8).

Cell structure and metabolism

Aspergillus fumigatus is known to be a producer of various proteinases that are thought to aid in virulence, however their roles in doing so are largely unknown (4). They are thought to be able to break down barriers within the host to allow for entry. Evidence of this is found in the ability of proteinases secreted by the fungus to hydrolyze pulmonary basal lamina (4). Three proteinases that have been able to be identified are an alkaline proteinase, a metalloproteinase, and an aspartic proteinase (4). Contrary to other common fungal pathogens, human serum does not inhibit Aspergillus fumigatus from growing or secreting these proteinases. It has actually shown to stimulate growth and secretion by up to 80%. It is possible that the fungus uses the serum as a nutrient source, a topic of current research (4).

Also contrary to other fungal pathogens, this particular species does not use lipids and fatty acids as its primary carbon source during growth. It is currently thought, and being researched, that proteins from host tissue likely represent a major carbon source during growth (7).

Ecology/Pathology

Aspergillus fumigatus is found predominately in the soil. It is a saprophytic fungi that breaks down carbon and nitrogen from deceased hosts and plays a key role in compost piles (1). In the conidia form however, it can become airborne in the atmosphere and gain access to other hosts, including that of the human body.

As stated earlier, Aspergillus fumigatus is one of the most common of the genus Aspergillus to cause disease within immunocompromised individuals. The infections can range from allergies to life-threatening infections. It is an opportunistic fungus that enters the body through the lungs, and in individuals with suppressed immune systems can quickly spread to the blood stream, brain, and the rest of the body. Three of the most severe of the infections, also known as Aspergillosis, include Allergic Bronchopulmonary Aspergillosis, Aspergilloma, and Invasive Aspergillosis or IA. IA is known to have approximately three thousand cases a year with a mortality rate above 50% (1). In recent years, there has been an increase in Aspergillosis cases as a result of an increase in the use of immunosuppressive therapies. Those at risk include bone marrow recipients, organ transplant patients, cancer patients, and AIDS patients (4). Often diagnosis is difficult and occurs late. This is because of the fairly common symptoms of fever and respiratory problems (cough, chest pain, breathlessness, etc) that do not respond to antibiotics. Diagnosis is then often made via x-rays and blood tests. Current treatment with antifungal drugs shows limited effectiveness.

Infection occurs when conidia that are released into the atmosphere enter the lungs. It is estimated that several hundred conidia are inhaled by an individual throughout the day. In most cases the immune system is able to fight off advances (1). However in immunocompromised individuals, it is thought the conidia gain entrance into the body by secreting proteinases able to break down barriers found in the lungs. As mentioned earlier, three proteinases have been identified that aid in the virulence of the fungus; however strains lacking any number of these proteinases still maintained levels of virulence (4).

Current Research

1.Using a isocitrate lyase mutant, it was shown that Aspergillus fumigatus does not require fatty acid metabolism to develop and subsequently cause Aspergillosis within its host. As a result of this, research continues to find the carbon source that is used to aid in the fungi’s developments. Currently research is being done to test the hypothesis that carbon is retrieved from proteins released from the host’s tissue (7).

2.Because of its environment Aspergillus fumigatus it is often exposed to fluctations in pH and temperature, as well as reactive oxygen species. Current research has focused on how the fungus deals with this. A stress response regulated by cAMP-dependent protein kinase (PKA) plays a role in regulating the growth and virulence of the fungus. It has been shown in experiments that mutants for the regulatory subunit of PKA are more susceptible to oxidative damage and abnormalities in the conidia, hindering its ability to become airborne and taken in by individuals(6).

3.A current research study has attempted to further explain how Aspergillus fumigatus gains access into the body via the lungs. In this study, the interaction between the conidia and the alveolar macrophage was looked at. It was found that the conidia are able to inhibit caspase 3 by an unknown mechanism, thereby inhibiting host cell apoptosis of alveolar macrophages (9).

References

1.Latge, Jean-Paul. Aspergillus Fumigatus and Aspergillosis. Clin Microbial Rev. 12, 310-350 (1999).

2.Gow, Neil A.R. Fungal Genomics: Forensic Evidence of Sexual Activity. Current Biology, Vol. 15, pR509-R511 (2005).

3.Arnaud Firon, François Villalba, Roland Beffa, and Christophe d'Enfert. Identification of Essential Genes in the Human Fungal Pathogen Aspergillus fumigatus by Transposon Mutagenesis. Eukaryot Cell. April 2(2), pg 247-255 (2003).

4.Anna H. T. Gifford, Jodine R. Klippenstein, and Margo M. Moore. Serum Stimulates Growth of and Proteinase Secretion by Aspergillus fumigatus. Infection and Immunity 70(1), pg 19-26 (2002).

5.Paoletti, Mathieu et al. Evidence for Sexuality in the Opportunistic Fungal Pathogen Aspergillus fumigatus. Current Biology 15(13) pg 1242-1248 (2005).

6.Zhao, Wei et al. Deletion of the Regulatory Subunit of Protein Kinase A in Aspergillus fumigatus Alters Morphology, Sensitivity to Oxidative Damage, and Virulence. Infection and Immunity 74(8), pg 4865-4874 (2006).

7.Schöbel, Felicitas et al. Aspergillus fumigatus Does Not Require Fatty Acid Metabolism via Isocitrate Lyase for Development of Invasive Aspergillosis. Infection and Immunity 75(3), pg 1237-1244 (2007).

8.Nierman, William C. et al. Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus. Nature 438(22), pg 1152-1156 (2005).

9.Katrin Volling, Axel A. Brakhage, Hans Peter Saluz. Apoptosis inhibition of alveolar macrophages upon interaction with conidia of Aspergillus fumigatus. FEMS Microbiology Letters (Online Early Articles) Aug. 20, 2007.


Edited by Paul Schaefer, student of Rachel Larsen

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