Drug-resistant mold spreads and infects the lungs of susceptible people

A new study from Imperial College London finds that drug-resistant mold spreads from the environment and infects the lungs of susceptible people.

Researchers found six cases of people being infected with a drug-resistant form of a fungus called Aspergillus fumigatus that could be traced to spores in the environment. Their findings use samples from England, Wales, Scotland and Ireland, and are published in Natural microbiology.

Aspergillus fumigatus is an environmental mold that can cause fungal lung disease. While people with healthy lungs clear inhaled spores, people with lung conditions or weakened immune systems sometimes cannot, which means the spores can stay in the lungs and cause an infection called aspergillosis. Aspergillosis affects 10 to 20 million people worldwide. The infection is usually treated with an antifungal drug, but emerging resistance to these drugs has been reported.

This resistance has evolved due to the widespread agricultural use of azole fungicides, according to the researchers. Azole drugs that work similarly are the first-line treatment for patients infected with the mold Aspergillus fumigatus, so exposure of the fungus to azole fungicides in the environment means it is often in a resistant form. drugs before he even meets the people he infects.

The researchers call for greater surveillance of Aspergillus fumigatus in the environment and the clinic to help understand the risk it poses.

Understanding the environmental hotspots and genetic basis for the evolution of fungal drug resistance requires urgent attention, as resistance compromises our ability to prevent and treat this disease. The prevalence of drug-resistant aspergillosis has risen from negligible levels before 1999 to 3-40% of cases today across Europe. At the same time, more and more people may be susceptible to Aspergillus fumigatus infection due to the growing number of people receiving stem cell or solid organ transplants, undergoing immunosuppressive therapy, or suffering from lung or severe viral respiratory infections.

Matthew Fisher, Senior Author, Professor, Imperial School of Public Health

In the study, researchers isolated 218 samples of Aspergillus fumigatus across England, Wales, Scotland and Ireland between 2005 and 2017. About 7 in 10 samples were from infected people (153 samples from 143 patients in five hospitals) and the rest came from the environment (65 samples) – including soil, compost, plant bulbs, air and other sources.

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

They found six strains of Aspergillus fumigatus that existed in the environment and that had infected six patients. The researchers say the genetic similarities indicated that the fungus had spread from the environment to the patient.

Lead author Dr Johanna Rhodes, from the Imperial MRC’s Center for Global Disease Analysis within the School of Public Health, says: “Increasingly, clinically seen cases of aspergillosis are resistant to first-line azole drugs.However, we don’t know how patients get these infections – whether they develop in the lungs while the infection is being treated or whether the mold spores that infect them are resistant to drugs in the first place.Our study finds that both routes of infection are possible and confirms concerns that pre-resistant mold spores from the environment can enter and infect people’s lungs, causing disease that is more difficult to treat. .”

Of the 218 samples, almost half (106 samples) were resistant to at least one of the first-line azole drugs used in the clinic. Specifically, 48% (104 samples) were resistant to itraconazole, 29% (64 samples) to voriconazole, and 21% to posaconazole. More than 10% of samples (26, including 23 environmental and 3 patient samples) were resistant to two or more azole drugs.

In the 218 samples, the researchers found 50 new genes associated with drug resistance. Digging deeper into the DNA, they also found five new combinations of single-digit changes in DNA (called single nucleotide polymorphisms, or SNPs) associated with drug resistance, including one multi-drug resistant.

By examining the genes of the Aspergillus fumigatus samples, the researchers discovered that there were two distinct groups: group A (123 of 218 samples) and group B (95 samples). About 80% of Group A samples were drug resistant, while about 85% of Group B were not. While the two groups were distinct, the researchers found signs of exchanging genetic material and, in some cases, creating new versions of drug resistance.

The researchers say these findings indicate that the full spectrum of azole resistance in Aspergillus fumigatus has yet to be understood.

Dr Rhodes says: “Our findings highlight new routes of transmission of resistant infections to humans and demonstrate the need to better understand where and how Aspergillus fumigatus generates drug resistance.