Aspergillus infections: resistance to azole treatment increased in the presence of diesel particles

The dose of itraconazole necessary to reach the minimal inhibitory concentration (MIC) for Aspergillus fumigatus was more than 64-fold in the presence of diesel particles in the growth medium. Thus, diesel pollution may be influential for resistance to antifungal treatment of Aspergillus infections.

The fungal pathogen A. fumigatus releases spores that may cause severe infections, especially in immunocompromised patients and several respiratory conditions like COPD, asthma, and cystic fibrosis [1,2]. Valentina Huang (Imperial College London, UK) pointed out that the increased use of antifungal agents in the last decades has led to a worldwide surge in azole-resistant Aspergillus infections [1]. To shed further light on the possible influence of air pollution on the emergence of this azole resistance, the researchers performed passaging of A. fumigatus in Sabouraud dextrose agar with and without diesel particles, using rising concentrations of itraconazole. Comparing susceptibility testing observed an appropriate correlation between the visual readings for MIC and absorbance results, thus the latter was used for further analyses. The MIC results of the passages were compared with the expected ranges of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) of the A. fumigatus strain ATCC204305. Apart from assessing MIC, genetic analyses were also performed.

Overall, a decreased susceptibility was determined with a 2 to 4 times higher itraconazole concentration needed for MIC. However, in the passages with diesel particles, the MIC for the azole was over 64-fold. In terms of genetics, the reverse transcription PCR analysis revealed a 2-fold expression of the fungal CYP51 protein in the presence of diesel compared with passages without. Results for drug efflux mediated by membrane transporters and Sanger sequencing for mutation on the CYP51A gene found no significant changes.

The authors expressed that these findings demonstrate the accelerated evolution of resistance against azole antifungal agents in the presence of diesel particles, but they also stated that further genetic analysis will be required to identify the underlying resistance mechanisms.

1. Ito K, et al. Accelerated evolution of azole resistant Aspergillus fumigatus by diesel particles. Abstract 2182, ERS International Congress 2023, 9–13 September, Milan, Italy.
2. Sen P, et al. Drug Target Insights. 2022;16:25-35.

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Posted on 29 October, 202329 October, 2023