Aspergillus fumigatus

About this image:

The electron microscope image shows a  white blood cell (neutrophil granulocytes, grey) ingesting several attached spores of Aspergillus fumigatus (conidia, green).

Members of the genus Aspergillus are molds growing in the form of filaments (hyphae) composed of multiple cells. Aspergillus spores (specialized cell form for dispersal) are found in almost all oxygen-rich environments and are very common in the air we breath but generally they only cause health problems in individuals with weakened immune systems. Approximately 170 species of Aspergillus have been described but only about 20 have been found to cause disease. In humans, by far the most common disease causing species of Aspergillus encountered is Aspergillus fumigatus that can cause a group of diseases located within the body known as "invasive aspergillosis", which may be in the form of infections affecting one or multiple organs, bloodvessels and bloodstream or causing systemic poisoning. By far the most significant risk factor for aspergillosis is the status of the immune system of an individual. As such, aspergillosis mostly affects patients whose immune system’s ability to fight infectious diseases is reduced, especially those with cancer of the blood or bone marrow, patients undergoing chemotherapy, transplant patients and other diseases affecting the immune system such as HIV or AIDS, chronic granulomatous disease as well as other diseases such as chronic obstructive pulmonary disease or cystic fibrosis.

Invasive aspergillosis generally occurs in the lung or the air-filled compartments of the nose’s cavity but can also occur in the ear, eye or multiple other organs or sites within the body. The disease is characterized by acute inflammation and destruction of tissue (necrosis), although in patients with abnormally low number of white blood cells (neutropenia) the acute inflammatory response is greatly reduced. At the site of infection, A. fumigatus has a preference for invading blood vessels causing blockage and hence tissue death and necrosis with leakage of red blood cells into the surrounding tissue spaces. A diagnostic marker for invasive infection with this group of organisms is the microscopical identification of hyphae that are split into cells by internal cross-walls. However, unambiguous identification of A. fumigatus can only be made after culture or with molecular biology techniques (polymerase chain reaction).

Due to the the patient’s often severe underlying diseases and the difficulty of diagnosing fungal infections at an early stage, clinical cure of invasive fungal infections is difficult to achieve. For patients with invasive aspergillosis caused by A. fumigatus the mortality rate can be above 50%. Despite more options for treating patients with invasive fungal infections becoming available in the recent years, current drugs fighting fungal infection (antifungals) still have significant limitations. These relate mainly to administration, i.e. the need for fast and reliable uptake into the bloodstream, as well as safety and tolerability. Further, functional impairment of organs such as kidney or liver and potential drug-drug interaction prevent the use of some antifungals. Hence, new treatment options for patients with invasive aspergillosis are urgently required.

Image credit: Priyanka Narang, Manfred Rohde, and Matthias Gunzer, Helmholtz Centre for Infection Research. (2007) PLoS Pathogens Issue Image | Vol. 3(2) February 2007. PLoS Pathog 3(2): ev03.i02. doi: 10.1371/image.ppat.v03.i02