Veterinarian discovers new fungal species

Aspergillus felis identified in cats, dogs and humans

July 3, 2013 (published)
By Phyllis DeGioia

Photo courtesy of Dr. Vanessa Barrs
This Cornish Rex is seen with exophthalmos and third eyelid prolapse associated with a left retrobulbar fungal granuloma caused by A. felis before and after treatment.
A veterinarian in Australia has identified a previously unknown species of fungus that can infect cats, humans and dogs with life-threatening consequences.

Dr. Vanessa Barrs, a clinician and researcher at the University of Sydney's Faculty of Veterinary Science, says mold spores isolated from three cats presenting in 2006 with tumor-like growths in their eye sockets and nasal cavities initially were mistaken for Aspergillus fumigatus, a common fungus known to infect humans and other animals worldwide.

However, six years of research revealed the infection stemmed from a new fungus species — one she's named Aspergillus felis.

Findings from Barrs and her colleagues recently were published by the open-access online science and medicine journal PLOS ONE. In the article, lead author Barrs describes how she came across three cats presenting with unusual sinonasal or sino-orbital fungal infections at the University of Sydney's Valentine Charlton Cat Centre (VCCC).

Initial cultures examined by the university's Centre for Infectious Diseases at Westmead Hospital identified the fungus as A. fumigatus. But that was simply the closest match, and treating the infections was unusually difficult. The fungus proved resistant to powerful anti-fungal drugs typically used to treat A. fumigatus cases.

That's when Barrs suspected she might be dealing with an unknown pathogen. "I began to recruit cases for a prospective study including cats presented to the VCCC and fungal cultures submitted from veterinarians around Australia who were seeing similar cases," she said in an email interview with the VIN News Service. 

Six years of investigation followed. Barrs examined several areas of the fungus's genome and did mating studies to see if the fungi in her samples were able to sexually reproduce.

The result: Barrs discovered that A. felis can reproduce asexually and sexually. All Aspergillus fungi reproduce asexually by a process of mitosis, where the fungal filaments called hyphae elongate and produce asexual spores called conidia. Some Aspergillus species also can reproduce sexually if two colonies of opposite mating type grow together in the environment; their fungal hyphae fuse together and they reproduce by a process of meiosis where they produce sexual spores.

Photo by Dr. Vanessa Barrs
In this axial CT scan, the exophthalmos and third eyelid prolapse associated with a left retrobulbar fungal granuloma caused by A. felis is clearly seen in the left ventromedial orbit with invasion of paranasal soft-tissues.
The new fungal species is heterothallic, meaning it requires two compatible partners to produce sexual spores. It has a fully functioning reproductive cycle, can readily mate with partners of an opposite mating type and can produce sexual spores within seven to 10 days, Barrs explained.

That finding led Barrs to wonder whether the fungus she was dealing with was A. viridinutans, another Aspergillus species. For further analysis, she called on renowned mycologist Robert Samson and his team at the CBS Fungal Biodiversity Centre, an institute of the Royal Netherlands Academy of Arts and Sciences in Utrecht.

Eventually, with the help of research teams at the CBS Fungal Biodiversity Centre as well as medical doctors and veterinarians from Australia, Netherlands, United Kingdom and Hungary, Barrs authored a paper on sinonasal and sino-orbital aspergillosis, describing the syndrome of upper respiratory aspergillosis in 23 cats. It was published in the January 2012 edition of The Veterinary Journal.

That's when more suspected cases of the new fungal species started coming to light. In the U.K., a veterinarian sent a feline fungal culture for analysis at the Regional Mycology Laboratory at the University Hospital of South Manchester. Results showed A. felis. And an article in Medical Mycology described a 56-year-old man in Portugal whose atypical pneumonia had been associated with A. viridinutans. The patient developed chronic invasive pulmonary aspergillosis, and the infection lasted more than 18 months.

Barrs thought the case sounded familiar to what she was seeing in feline patients: the condition was chronic, and the infection could move from tissue to bone or the brain. The pathogen showed resistance to some anti-fungal medications. Barrs contacted the authors and joined their research team. A fungal culture from the 56-year-old man proved to be the the first documented isolate of A. felis from a human patient.  

So far, A. felis has been documented in two humans, and researchers are trying to understand the range of clinical syndromes associated with infection. The second human patient had leukemia and invasive pulmonary aspergillosis. The humans with A. felis had fungal pneumonia, but unlike cats, they had no disease in their eye sockets.  

A. felis is one of more than 250 species of Aspergillus. Aspergillus species are ubiquitous organisms that obtain nutrients from dead organic matter and opportunistic pathogens; they decay vegetation in soil and help recycle carbon and nitrogen, Barrs said. Some Aspergillus species are more prevalent in certain geographic regions. The abundant spores of Aspergillus species are aerosolized and disseminated widely via air currents. Humans generally inhale hundreds of Aspergillus spores every day, and those with a normal immune response can expel them. 

Photo by Julia Beatty
Dr. Vanessa Barrs, seen with her cat Bobby-Rae, was the primary researcher on the project and chose the name of the new fungal species.
Now that it's identified, Barrs expects to start hearing about A. felis infections with greater frequency.

"We have now detected A. felis in cats from Australia, the United Kingdom and more recently Belgium, although that is unpublished," Barrs said. "I suspect that recent reports of A. viridinutans from cats with SOA (sino-orbital aspergillosis) in Japan could also be due to A. felis infection. I do think A. felis is likely to be detected as a causative agent of SOA in cats worldwide and that infections will be documented in other mammals and also in birds. A. felis is extremely similar in morphological appearance to A. fumigatus, and reliable identification requires molecular methods, which are becoming more widely available." 

Barrs and her colleagues estimate the survival rate of cats with A. felis is 15 percent. Cats with sinonasal aspergillosis caused by A. felis have a better prognosis, she said, noting a greater than 75-percent response rate to treatment. 

So far, A. felis has been documented in one immunocompromised dog that was being treated for immune-mediated hemolytic anemia, and the infection was fatal. Barrs believes it is possible that some cases of disseminated aspergillosis in dogs previously attributed to A. fumigatus could have been caused by A. felis. However, recent molecular research conducted by her group shows that greater than 98 percent of cases of SOA in dogs are caused by A. fumigatus.  

The next step for Barrs and her research colleagues is to identify whether some human patients in Australia diagnosed with fungal disease actually have A. felis. She also plans to continue veterinary research on other species of Aspergillus and mycotic infections in dogs and cats.  

"We are interested in why apparently systemically immunocompetent cats that test negative for feline immunodeficiency virus and feline leukemia virus are susceptible to A. felis infection," Barrs said.

Of the more than 55 cases of upper respiratory aspergillosis reported in cats, more than a third were brachycephalic, mostly of Persian or Himalayan breeds. Barrs said she's interested in researching why these cats are susceptible to infection with the ultimate aim of improving treatment outcomes.  

As for the once-in-a-lifetime opportunity to name a new species, Barrs followed her heart.  

“Everyone asks me why I didn’t call it Aspergillus Barrsei!” she said. “I wanted to name this fungus after the host in which it was first discovered: the domestic cat. These infections are so devastating in cats, and during the course of the investigations, it was heartbreaking to treat some cats that, despite months of treatment with powerful anti-fungal drugs, developed progressive disease with neurological involvement. So I named the fungus in memory of these cats.”

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