Removing a core septin gene from Aspergillus fumigatus turned caspofungin from a drug that merely halts the fungus into one that kills it, in both laboratory and animal tests.
Aspergillus fumigatus is a mould that most people inhale without consequence. Its spores are everywhere — in compost, in soil, in household dust — and a healthy immune system disposes of them without the host ever noticing. For people whose immune systems are compromised, the same spores can establish a rapid and severe respiratory infection with a mortality rate that remains, even with treatment, between 30 and 90 per cent.
A study in Molecular Biology of the Cell from a team at Virginia Tech and collaborating institutions reports a way to make one of the available drugs substantially more effective, by identifying what the fungus is doing to survive it.
A drug that stops the fungus without killing it
Triazoles are the frontline treatment for invasive aspergillosis. When they fail — and resistance is spreading — the second line is a class called echinocandins, of which caspofungin is one. Echinocandins work by interfering with construction of the fungal cell wall, and their limitation is written into how they are classified: against Aspergillus they are fungistatic rather than fungicidal. They stop the fungus from growing. They do not kill it.
For a patient whose immune system cannot finish the job, that distinction matters enormously. A halted infection in an immunocompromised host is an infection waiting for the drug to be withdrawn.
The team’s approach was to ask what the fungus relies on to survive the drug’s assault on its cell wall. They engineered strains lacking particular cell-wall-regulating proteins and then applied the echinocandin. In one case the drug killed the modified fungus outright, in laboratory culture and in animal tests. The gene whose deletion produced that effect, named in the paper’s title, is aspB, a core septin gene — septins being a family of proteins involved in organising the cell membrane and cytoskeleton, including at sites where new wall is being built.
The result identifies aspB as the protein most responsible for the fungus’s ability to tolerate echinocandin treatment. That makes it a drug target: a compound that inhibited the septin would, in principle, convert caspofungin from a holding action into a cure.
Ten drugs against hundreds
The study’s significance is best understood against how thin the antifungal arsenal is. “When it comes to antifungal drugs, there are very few options available compared to antibacterial drugs,” said Rebecca Jean Busch, a doctoral candidate in biological sciences at Virginia Tech who led the study. “We have hundreds of antibacterial drugs, and we have somewhere around 10 [antifungal drugs].”
The reason for the gap is biological. Fungi are eukaryotes, as humans are, which means the cellular machinery a drug might attack is often machinery our own cells also use. Antibacterial drugs can exploit the many fundamental differences between bacterial and human cells; antifungal drugs have far fewer such openings. The cell wall, which human cells lack entirely, is one of the few clean targets available — which is why making the drugs that attack it work better is a disproportionately valuable goal.
“Once you get a strain of the fungus that’s resistant, it’s like, what else do we treat you with?” Busch said.
That question is becoming less hypothetical. “Even with treatment, the mortality rate can vary between 30-90 percent,” said José M. Vargas-Muñiz, an assistant professor of biological sciences at Virginia Tech, who was part of the team. “And now environmentally acquired antifungal-resistant Aspergillus are starting to infect patients.” Resistance arising in the environment rather than in the patient is a particular problem, because it means a person can be infected with a resistant strain from the outset, before any drug has been administered.
Who is at risk, and why it is missed
The population vulnerable to invasive aspergillosis is larger and less obvious than it may appear. It includes people with blood cancers, transplant recipients and others with profoundly suppressed immunity, but Busch notes it also extends to some people taking immune-modulating drugs for conditions such as psoriasis or rheumatoid arthritis — treatments taken by many people who would not describe themselves as immunocompromised.
Diagnosis is a further obstacle. “There’s a lot of people who just don’t know that these terrible fungal diseases exist,” Busch said. “This is different; it’s an invasive fungal infection and hard to diagnose unless the doctors already kind of know what they’re looking for.” An infection that progresses quickly and is difficult to identify is one where delay is costly.
The authors put the economic burden at roughly $1.3 billion a year in the United States, describing it as the highest per-patient cost of any invasive fungal disease.
Groundwork, not a treatment
Busch is measured about what the work delivers. “It lays the groundwork for the future,” she said — and that is the right framing. Deleting a gene in a laboratory strain is not the same as inhibiting its protein product with a drug in a patient. Septins are present in human cells too, which raises the question of whether a septin inhibitor could be made selective enough for fungi to be safe, and the release says nothing about that. Nor does it report how many animals were tested, what the survival figures were, or which animal model was used.
Two documentation gaps are worth flagging. The release lists no funding sources and includes no conflict-of-interest statement. It also carries an internal date inconsistency: the release is dated 1 October 2026 while giving the article’s publication date as 16 October 2026, two weeks later.
What remains is a specific, testable target in a disease with few of them: a single fungal protein whose absence turns an existing, approved drug from containment into cure.
Notes
- “Deletion of core septin gene aspB in Aspergillus fumigatus results in fungicidal activity of caspofungin.” Molecular Biology of the Cell, 16 October 2026. DOI: 10.1091/mbc.E26-03-0151.
- Virginia Tech. “A deadly fungus may not live to see the last of us.” EurekAlert!, 1 October 2026. https://www.eurekalert.org/news-releases/1146222.