Scientists determine drug-resistant mold that infects human lungs

According to a recent study conducted by Imperial College London, drug-resistant mold is disseminated from the environment and affects the lungs of those who are susceptible.

Scientists determine drug-resistant mold that infects human lungs

Image Credit: Imperial College London

The scientists determined six cases of humans infected with Aspergillus fumigatus, a drug-resistant fungus that they linked to spores in the environment. Their findings, which were published in Nature Microbiology, were based on samples from England, Wales, Scotland, and Ireland.

Aspergillus fumigatus is a fungal lung disease-causing mold found in the environment. People with healthy lungs can remove inhaled spores, but those with lung diseases or poor immune systems may not be able to, resulting in the spores remaining in the lungs and producing aspergillosis.

Aspergillosis is a fungal infection that affects 10–20 million individuals globally. Antifungal medicines are commonly used to treat the illness, however, growing resistance to these drugs has been noted.

According to scientists, this resistance has arisen as a result of the widespread use of azole fungicides in agriculture. Azole medications that function similarly are the first-line treatment for people infected with the Aspergillus fumigatus mold, thus the fungus’ access to azole fungicides in the environment implies it is often drug-resistant before it attacks people.

The researchers recommend that Aspergillus fumigatus be monitored more closely in the environment and clinics to better understand the harm it poses.

Understanding the environmental hotspots and genetic basis of evolving fungal drug resistance needs urgent attention because resistance is compromising our ability to prevent and treat this disease.”

Matthew Fisher, Study Senior Author and Professor, School of Public Health, Imperial College London

The prevalence of drug-resistant aspergillosis has grown from negligible levels before 1999 to up to 3-40% of cases now across Europe,” he added.

Fisher further states, “At the same time, more and more people might be susceptible to Aspergillus fumigatus infection because of growing numbers of people receiving stem cell or solid organ transplants, being on immunosuppressive therapy, or having lung conditions or severe viral respiratory infections.”

Study confirms infection concerns

Between 2005 and 2017, the scientists isolated 218 Aspergillus fumigatus samples from England, Wales, Scotland, and Ireland for the research. Around 7 out of 10 samples were from infected individuals (153 from 143 patients in five hospitals) and the rest (65 samples) came from the surroundings, including soil, compost, plant bulbs, the air, and other factors.

The scientists analyzed the DNA recovered from the sample molds to see if there was a convergence in the resistant spores found in the environment and certain patients.

They discovered six Aspergillus fumigatus strains in the environment that had infected six people. The genetic traits, according to the researchers, suggested that the fungus had transferred from the atmosphere to the patient.

Increasingly, the cases of aspergillosis seen in the clinic are resistant to first-line azole drugs.”

Dr Johanna Rhodes, Lead Author, MRC Centre for Global Disease Analysis, School of Public Health, Imperial College London

However, we’ve not been sure how patients are acquiring these infections—whether they develop in the lungs during treatment for the infection, or whether the mold spores that infect them are drug-resistant in the first place,” she says.

Dr Rhodes also comments, “Our study finds that both routes of infection are possible and confirms concerns that pre-resistant mold spores in the environment are able to enter and infect people’s lungs causing harder-to-treat disease.”

Almost half of the 218 samples (106 samples) were subject to at least one of the clinic’s first-line azole medications. Itraconazole resistance was found in 48% (104 samples), voriconazole resistance in 29% (64 samples), and posaconazole resistance in 21%. More than 10% of the samples (26 in total, 23 from the environment, and 3 from patients) were susceptible to two or more azole medications.

The scientists determined 50 novel genes linked to medication resistance among the 218 samples. They also discovered five novel combinations of single-digit alterations in the DNA (named single nucleotide polymorphisms, or SNPs) that were linked to medication resistance, some of which were resistant to multiple treatments, after digging further into the DNA.

When the researchers looked at the genes of the Aspergillus fumigatus samples, they discovered two unique groups: group A (123 of the 218 samples) and group B (95 samples). About 80% of samples in group A were resistant to drugs, whereas roughly 85% of samples in group B were not. While the two groups were separate, the scientists discovered evidence of genetic material swapping and, in some instances, the creation of new drug resistance variants.

These data, according to the researchers, imply that the complete spectrum of azole resistance in Aspergillus fumigatus is still unknown.

Dr Rhodes concludes, “Our findings highlight new ways of resistant infections passing to people and show that a better understanding of where and how Aspergillus fumigatus is generating drug resistance is needed.”

Source:
Journal reference:

Rhodes, J., et al. (2022) Population genomics confirms acquisition of drug-resistant Aspergillus fumigatus infection by humans from the environment. Nature Microbiology. doi.org/10.1038/s41564-022-01091-2.

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