Tool Unlocks Genetic Secrets of Pneumocystis Fungi

Researchers use extracellular vesicles to deliver gene-editing tools and study this difficult-to-culture pathogen.

Jan. 28, 2026 at 7:39pm

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Researchers at the University of Cincinnati College of Medicine have developed a new tool that uses extracellular vesicles (EVs) from mouse lungs to deliver gene-editing molecules into Pneumocystis murina, a species of fungus that infects mice. This approach allows them to genetically modify the fungus and study its genetic machinery, which has long been poorly understood due to the difficulty of culturing Pneumocystis in a lab. The researchers say this strategy could extend beyond Pneumocystis to other obligate fungal and host-restricted pathogens that have resisted traditional laboratory manipulation.

Why it matters

Pneumocystis is a genus of fungal pathogens that cause severe pneumonia, particularly in immunocompromised people like those with HIV/AIDS or who have received organ transplants. However, the mechanisms by which it infects a host organism and acquires resistance to known treatments remain largely unknown, making it difficult to develop new therapeutics. This new tool provides a way to genetically modify Pneumocystis and study its genetic workings, which could lead to a better understanding of how it causes infection and resistance, potentially paving the way for improved treatments.

The details

The researchers used extracellular vesicles (EVs) from mouse lungs to deliver gene-editing molecules like CRISPR-Cas9 into Pneumocystis murina, a species that infects mice. This allowed them to successfully introduce genetic modifications into the fungus, which has been difficult to study in the lab since it only replicates in its mammalian host. The researchers were able to target a specific gene connected to resistance to a common prophylactic drug, which could help inform the development of better drugs, especially in parts of the world where people with compromised immune systems lack access to quality healthcare.

  • The study was recently published in the journal mBio in January 2026.

The players

A. George Smulian, M.D.

An infectious disease researcher and senior author on the study who has studied the genetic machinery of Pneumocystis for decades.

Steve Sayson, Ph.D.

A molecular biologist who led the study and had been studying extracellular vesicles within the host environment where Pneumocystis lives.

University of Cincinnati College of Medicine

The institution where the researchers who conducted this study are based.

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What they’re saying

“This really is the first use of host EVs as a transport mechanism to introduce DNA and nucleic acid material into pathogenic organisms.”

— A. George Smulian, M.D., Infectious disease researcher and senior author

“So now we're able to interrogate that process to say what's causing resistance. Maybe we can develop a better drug.”

— Steve Sayson, Ph.D., Molecular biologist and lead author

What’s next

The researchers say the next step is to find ways to better understand the genetic transformation initiated by the EVs, including controlling more genes and the level of expression.

The takeaway

This new tool provides a potential framework for delivering genetic tools into difficult-to-study pathogens like Pneumocystis, which could lead to a better understanding of how these fungi cause infection and develop resistance, ultimately informing the development of improved treatments.