Transcriptional profiles ofTrichophyton rubrumin response to itraconazole

Abstract

Trichophyton rubrum is the predominant causative agent for superficial dermatomycosis. In order to understand how triazole antifungal agents interact with dermatophytes, the gene expression response of T. rubrum to itraconazole was studied by large-scale gene expression profiling. A total of 670 genes were found to be responsive to itraconazole, including 305 that were up-regulated and 365 down-regulated. Most genes involved in lipid metabolism and especially in ergosterol biosynthesis were up-regulated in response to itraconazole, including ERG6, ERG7, ERG11, ERG24, ERG25 and ERG26. In addition, transcription of some genes involved in cell stress response, drug efflux, and small molecule transport was also affected by itraconazole. Differential expression of selected genes was confirmed by real-time reverse transcription polymerase chain reaction (RT-PCR). This is the first microarray hybridization analysis of T. rubrum exposed to a triazole antifungal agent.

Transcriptional profile of Paracoccidioides spp. in response to itraconazole

“…Similar and different groups were also observed in other fungi in response to different azoles [8,9,11,12,15] (Figure 5). Among the genes affected, we identified genes in common with other fungi, as well as genes unique to Paracoccidioides .…”

“…Because ERG transcripts and proteins levels were changed in the presence of azoles in fungi such as T. rubrum [9], S. cerevisiae [8], C. albicans [11,12] and A. fumigatus [13] we investigated whether ergosterol synthesis-related transcripts such as lanosterol 14 α-demethylase ( ERG11 ), C5,6-desaturase ( ERG3 ), delta-24-sterol C-methyltransferase ( ERG6 ), C-22 sterol desaturase ( ERG5 ) and C-4 methyl sterol oxidase ( ERG25 ) were changed in Paracoccidioides Pb 01 after 1 h, 2 h and 6 h of exposure to itraconazole using specific oligonucleotides in qRT-PCR. The results showed that all transcripts were increased at all time points (Figure 2B).…”

“…The global response to azoles, including itraconazole, of fungi such as Saccharomyces cerevisiae [8], Trichophyton rubrum [9], Aspergillus fumigatus [10] and Candida albicans [11,12] has been studied using transcriptional and proteomic approaches. In general, the findings revealed both specific and nonspecific antifungal-induced changes in gene and protein regulation.…”

Dermatophyte Virulence Factors: Identifying and Analyzing Genes That May Contribute to Chronic or Acute Skin Infections

“…In order to identify additional factors that play a role during infection, investigators have examined the transcriptional response of dermatophytes exposed to environmental factors such as growth on lipids [37, 38], changes in pH [38, 39], and the presence of antifungal drugs [38, 40–45]. They have also assessed transcript abundance during different stages of growth [46–49].…”

In Vitro and In Vivo Assessment of Dermatophyte Acquired Resistance to Efinaconazole, a Novel Triazole Antifungal

“…Using a similar methodology, it was found that efinaconazole did not increase the MIC in one Trichophyton mentagrophytes strain (data not shown). Antifungal drug exposure is believed to induce a stress response in fungal cells, leading to decreased drug susceptibility via a variety of mechanisms, such as the induction of drug efflux pumps (13). To assess the effects of efinaconazole exposure on the susceptibility of T. rubrum to commercially available antifungal drugs, the MICs of itraconazole, terbinafine, amorolfine, and ciclopirox were also determined.…”