Fungi can cause a range of infections and problems for humans. However, despite the fact that we encounter and inhale fungal spores nearly every time we step outside, we don’t often end up with a fungal infection. Why is that? The truth is, our immune systems have developed mechanisms to detect and destroy fungal spores that enter our bodies before they have time to grow, replicate, and cause a full-blown infection.
However, while the human body is designed to easily fight off fungal infections, this is not necessarily the case for people who have compromised immune systems. In fact, for immunocompromised people, the fungus Aspergillus fumigatus (A. fumigatus) can cause a serious pulmonary infection with a mortality rate as high as 50%.
There is a medication that exists to treat this type of fungal infection: caspofungin. However, in high enough doses, caspofungin has the opposite of its intended effect: rather than reducing fungal loads in the body, it can increase fungal growth. Until now, however, researchers did not have a clear sense of why this was happening.
Researchers at the University of Massachusetts—Amherst have conducted a full genomic analysis of A. fumigatus to better understand why this particular treatment sometimes makes infections worse. Their work is described in a recent article published in Microbiology Spectrum.
The research team, a collaboration between researchers from Vanderbilt University, The University of Tennessee, and the University of São Paolo were able to identify two genes in A. fumigatus that appear to contribute to the unfortunate effects of caspofungin.
The team sequenced the genomes of 67 samples looking for answers to how different gene variations could lead to fungal growth in people who receive high doses of caspofungin. Using CRISPR, researchers were able to remove the two identified genes, which helped confirm the paradoxical effect of caspofungin.
Researchers hope to further study these genomes and identify other genes that could contribute to the negative effects of caspofungin. The hope is to develop more targeted drugs that could eliminate the shortcomings of caspofungin.