Compensatory expression of multidrug-resistance genes encoding ABC transporters in dermatophytes.
Genomic sequencing of several dermatophyte species has revealed that they show small differences in genetic content and genome organization, although each fungus has adapted to specific niches. Thus, it seemed relevant to compare gene expression between species. Here, we examined the transcription modulation of three ATP-binding cassette (ABC) transporter genes (pdr1, mdr2 and mdr4), which code for membrane transporter proteins in four species of Trichophyton ; T. interdigitale, T. rubrum, T. tonsurans and T. equinum . These fungal species were challenged with sub-lethal doses of griseofulvin, itraconazole, terbinafine and amphotericin B. A mutant strain of T. interdigitale, Δmdr2, was also analysed for the modulation of pdr1 and mdr4 genes to evaluate the possible functional interaction among these three genes. Disruption of the mdr2 gene resulted in the accumulation of high levels of mdr4 transcripts when challenged with griseofulvin, suggesting that the mdr4 gene is compensating for the inactivation of mdr2 by providing resistance to this antifungal. Although the three ABC transporter genes have high homology between the four dermatophytes analysed, it is likely that they have specific functions, suggesting that the action of each drug is dependent on other factors inherent to each species. Our data suggest that these ABC transporter genes act synergistically in dermatophytes, and they may compensate for one another when challenged with antifungal drugs. This may be an important cause of therapeutic failure when treating fungal infections.
Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, 14049-900 Ribeirão Preto, SP, Brazil.
Maíra Pompeu
MP
Martins
Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, 14049-900 Ribeirão Preto, SP, Brazil.
Ana Carolina Capovilla
ACC
Franceschini
Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, 14049-900 Ribeirão Preto, SP, Brazil.
Tiago Rinaldi
TR
Jacob
Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, 14049-900 Ribeirão Preto, SP, Brazil.
Antonio
A
Rossi
Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, 14049-900 Ribeirão Preto, SP, Brazil.
Nilce Maria
NM
Martinez-Rossi
D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics; D000935:Antifungal Agents / Q000494:pharmacology*; D026141:Drug Resistance, Multiple, Fungal; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D055786:Gene Knockout Techniques; D019450:Genes, MDR; D014158:Transcription, Genetic; D014249:Trichophyton / Q000187:drug effects* / Q000235:genetics*
D018528:ATP-Binding Cassette Transporters; D000935:Antifungal Agents