Researchers discover that drug-resistant mold can infect people

Imperial College London’s new study has found that drug resistant mold is spreading from the surrounding environment and infecting people’s lungs.

Six cases of Aspergillus fumigatus infection were found by the researchers. The environment could have been responsible for their discovery. Their findings were published in the journal Science. Nature Microbiology.

Aspergillus fumigatus, an environmental mold, can cause fungal lung diseases. People with healthy lungs can remove inhaled spores easily, but people with weakened immune systems or lung conditions may not be able to do so. This can lead to an infection called aspergillosis. Aspergillosis is a condition that affects between 10-20 million people around the world. Usually, the infection can be treated with an antifungal drug. However, resistance has been reported.

Researchers say this resistance evolved due to the widespread use of azolefungicides in agriculture. Similar-effect azole drugs are used as the first-line treatment of patients with Aspergillus fumigus mold infection. This is because the fungus’ exposure in the environment to azolefungicides means that it is often drug-resistant before it ever encounters the people infected.

The researchers recommend that Aspergillus fumigatus be monitored more closely in the clinic and in the environment to understand the risks it poses.

Professor Matthew Fisher from Imperial’s School of Public Health is the senior author. He says: “Understanding both the environmental hotspots as well as genetic basis of evolving fungal drugs resistance must be urgently addressed, because resistance is compromising how we can prevent and treat this disease.”

He states that “the prevalence of drug-resistant Aspergillosis has increased from negligible levels prior to 1999 to up to 3-40% now across Europe.” Aspergillus fumigatus infection is increasing in people who are receiving stem cell or solid transplants, immunosuppressive therapy, have severe lung conditions, or are suffering from severe viral respiratory infections.

Researchers isolated 218 Aspergillus fusigatus samples from England and Wales, Scotland, Ireland, and Ireland between 2005-2017. Between 2005 and 2017, 75% of the samples were taken from patients (153 samples from 143 patients in five hospital). The rest (65 samples) were collected from the environment, including soil, compost, plants bulbs, and other sources.

The DNA was extracted from the sample molds by the researchers and sequenced to determine if there was crossover among the resistant spores that were found in the environment or in some patients.

Six strains of Aspergillus fusigatus were found in the environment that had infected six patients. Researchers concluded that the genetic similarities between the six strains of Aspergillus fumigatus were indicative that the fungus had spread from its environment to the patient.

Dr. Johanna Rhodes from Imperial’s MRC Center for Global Disease Analysis in the School of Public Health is the lead author. She says that “Increasingly, the cases of Aspergillosis seen at the clinic are resistant first-line azole medications. We don’t know how patients get these infections. It is possible that they develop in their lungs while they are receiving treatment. Or if the mold spores infecting them are resistant to drugs. Both routes of infection can be found in our study. This confirms the concern that mold spores that are resistant to treatment are capable of entering and infecting people’s lungs, causing more difficult-to-treat diseases.

Nearly half (106) of the 218 samples tested were resistant at least to one of the first-line anti-azole drugs used in clinic. 48% (104 samples), 29% (64 sample) to voriconazole and 21% (21 samples) to posaconazole were all resistant. More than 10% (26 samples, 23 environmental samples, and 3 samples from patients) were resistant at least two azole drugs.

The researchers discovered 50 genes that are associated with drug resistance in the 218 samples. They also discovered five new combinations of single-digit DNA changes (called single nucleotide Polymorphisms or SNPs) which were associated with drug resistance. One of these was resistant to multiple drugs.

Researchers looked at the genes in Aspergillus fumigatus samples and found two distinct groups: group A (123 of 218 samples) versus group B (95 samples). About 80% of the samples in group A were resistant to drugs, while 85% of those in group B were not. Although the two groups were quite distinct, researchers found evidence of them swapping genetic material. In some cases, they even created new forms of drug resistant.

These findings, according to the researchers, indicate that Aspergillus fumigatus has yet to fully understand the spectrum of azole resistance.

Dr. Rhodes states that “our findings highlight new ways in which resistant infections can be passed to people and show the need for a better understanding of how Aspergillus fumigatus generates drug resistance.”