Genetic Testing Reveals Often-Overlooked Fungal Infections in California Clinics

A new study published in JAMA Network Open reveals that a rarely diagnosed and frequently drug-resistant species, Aspergillus tubingensis, may be one of the most common causes of fungal infections in Southern California. Using genome sequencing, researchers found that this fungi is routinely misidentified as another fungal species, potentially masking its true impact on public health.

“We were expecting most of these infections to be caused by Aspergillus niger,” said Lance B. Price, senior author of the study, professor of environmental and occupational health at the George Washington University Milken Institute School of Public Health and visiting scholar at Statens Serum Institut in Copenhagen. “But the DNA sequencing data showed that the vast majority were actually Aspergillus tubingensis—a potentially more dangerous species that had been flying under the radar.”

The team analyzed more than 2,400 clinical samples from Kaiser Permanente Southern California between 2019 and 2023.

Nearly three-quarters of the samples initially identified as Aspergillus niger were actually Aspergillus tubingensis, their analysis found, and this misidentified fungus was frequently resistant to itraconazole and posaconazole, two triazole antifungals commonly used to treat serious fungal infections.

Identifying this confusion is important, researchers said, because triazole antifungals are first-line treatments for aspergillosis, a potentially life-threatening fungal infection. Resistance to these drugs is increasing in environmental fungi, which could compromise treatment for vulnerable patients.

Although often dismissed as an environmental contaminant, Aspergillus tubingensis was found in respiratory samples, suggesting it may be an underrecognized cause of invasive disease.

The study also raises questions about the role of agriculture in shaping fungal resistance. Like Aspergillus fumigatus, which has developed resistance due to widespread fungicide use, Aspergillus tubingensis is a soil-dwelling species that may be exposed to triazoles in vineyards, orchards, and other crops.

“California uses nearly 200,000 kilograms of triazole fungicides each year,” said Price. “We don’t know whether this widespread use is selecting for resistant Aspergillus tubingensis strains or simply boosting the environmental presence of the species, but both possibilities raise concerns and deserve further investigation.”

The researchers call for better fungal diagnostics in clinical laboratories, antifungal treatment guidelines specific to Aspergillus tubingensis and studies on agricultural fungicide use and its potential link to drug resistance.

“It’s not clear whether Aspergillus tubingensis infections are becoming more common or if we’ve just been missing them all along,” said Price. “But either way, we’re overdue for a closer look.”

The team is also working to identify what puts people at risk for Aspergillus tubingensis infections, which is a first step toward practical guidance on prevention.

Reference: Wang Y, Aziz M, Bush K, et al. Triazole resistance and misidentification of Aspergillus tubingensis in Southern California. JAMA Netw Open. 2025;8(12):e2543630. doi: 10.1001/jamanetworkopen.2025.43630

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