Abstract

Background: Aspergillus fumigatus is a common airborne fungal pathogen, which are colonised in asthma, COPD and CF lung. In the past few decades, increased usage of antifungal agents has led to a surge in azole resistant Aspergillus infections globally. Air pollution, a major source of chemicals and oxidants, causing DNA damage, is potentially a risk factor of mutations in microorganisms.

Objectives: We hypothesised that air pollutants such as diesel particles could accelerate the emergence of azole resistance in the presence of azole treatment.

Methods: A. fumigatus was passaged with escalating concentrations of itraconazole in the presence and absence of diesel particles in Sabouraud dextrose agar. Susceptibility testing (minimum inhibitory concentration (MIC) assay) to antifungal agents was then conducted, and gene expression of multidrug efflux transporters and CYP51A gene sequence were analysed by RT-PCR and Sanger sequencing.

Results: Passages of A. fumigatus with itraconazole caused 2-4-fold increase of MIC against itraconazole (reduced susceptibility) after passage 4, but when passaged with itraconazole in the presence of diesel particles, MIC of itraconazole became >64 fold higher than that for original fungus. No changes in CYP51A sequence and gene expression of multidrug efflux transporters were observed except for moderate induction of CYP51 protein.

Conclusions: Diesel particles were found to accelerate evolution of resistance against azole antifungal agents. Further gene analysis will be required to identify the underlying resistance mechanisms.