Diesel pollution increases Aspergillus fumigatus resistance to itraconazole by over 64 times, highlighting the need to identify resistance mechanisms.
The presence of diesel particles resulted in an over 64 times higher minimal inhibitory concentration (MIC) of itraconazole needed for Aspergillus fumigatus. This points to an increased advancement of azole resistance through diesel pollution, according to a study presented at the 2023 ERS International Congress.
Increasing resistance of A fumigatus to azole-based therapy has been noticed worldwide. As the airborne pathogen plays a role in several respiratory conditions like COPD, asthma and cystic fibrosis, Imperial College-based research investigated the possible influence of air pollution (ie, diesel particles), on the emergence of azole resistance.
The study performed passaging of A fumigatus in Sabouraud dextrose agar with and without diesel particles, using rising concentrations of itraconazole. Apart from assessing MIC assays, genetic analyses were also performed. 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 of the ATCC204305 A fumigatus.
Overall, a decreased susceptibility was determined with a two- to four-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 polymerase chain reaction analysis revealed a two-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 concluded 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 gene analysis is required to identify the underlying resistance mechanisms.
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