Fungal pathogen gene provides clues for treating aspergillosis

Image by US Department of Health and Human Services. - US Department of Health and Human Services, Center for disease control [2]., Public Domain, https://commons.wikimedia.org/w/index.php?curid=568269

Aspergillus fumigatus is a common fungus; it grows in many places including soil, plant matter, and dust around the world. It can also invade the human body. While most healthy people can eliminate A. fumigatus, the fungus can cause the disease known as aspergillosis in people with compromised immune systems.

 

A. fumigatus can bind to a protein in epithelial cells of the lungs, and evade elimination by taking up residence in phagosomes. Scientists from Leibniz Institute for Natural Product Research and Infection Biology have recently investigated how this pathogenic fungus disrupts a natural protective response in the lungs. The findings have been reported in Cell Host & Microbe (see: “Aspergillus fumigatus hijacks human p11 to redirect fungal-containing phagosomes to non-degradative pathway”).

 

Lung epithelial cells form a crucial barrier against pathogens in the air, including fungal spores. While these cells are not specialized pathogen destroyers like some immune cells, they can still surround foreign material and invaders, and lock them into compartments called phagosomes. The phagosome undergoes a maturation process, and the trapped invaders are eliminated.

 

The study has shown that fungal spores can alter this defensive response. A fungal protein made by A. fumigatus called HscA can bind to a human protein called p11, which triggers a series of events that stops the phagosome from degrading the fungus.

 

When the researchers eliminated the p11 protein, fungal spores in phagosomes are destroyed. If the fungal protein, HscA is switched off, the fungal spores are still destroyed. However, if the fungal and human proteins are functioning normally, the phagosomes never mature and the fungal spores are not destroyed. The investigators found that the fungi that remained in the immature phagosomes formed extensions called hyphae, and some spores were also released from the cell to cause infection in neighboring cells.

 

The researchers also found that the same mechanisms were at work in different immune cells.

 

The researchers also found that when people carry a certain mutation in their p11 gene, they are less likely to get aspergillosis. Hence, both Hsca and p11 could help treat aspergillosis.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)