Transporters in the Paracoccidioides brasiliensis transcriptome: insights on drug resistance.
In the struggle for life, the capacity of microorganisms to synthesize and secrete toxic compounds (inhibiting competitors) plays an important role in successful survival of these species. This ability must come together with the capability of being unaffected by these same compounds. Several mechanisms are thought to avoid the toxic effects. One of them is toxin extrusion from the intracellular environment to the outside vicinity, using special transmembrane proteins, referred to as transporters. These proteins are also important for other reasons, since most of them are involved in nutrient uptake and cellular excretion. In cancer cells and in pathogens, and particularly in fungi, some of these proteins have been pointed out as responsible for an important phenotype known as multidrug resistance (MDR). In the present study, we tried to identify in the Paracoccidioides brasiliensis transcriptome, transporter-ortholog genes from the two major classes: ATP binding cassette and major facilitator superfamily transporter. We found 22 groups with good similarity with other fungal ATP binding cassette transporters, and four Paracoccidioides brasilienses assembled expressed sequence tags that probably code for major facilitator superfamily proteins. We also focused on fungicide resistance orthologs already characterized in other pathogenic fungi. We were able to find homologs to C. albicans CDR1, CDR2, and MDR1, Saccharomyces cerevisiae PDR5 and Aspergillus AtrF genes, all of them related to azole resistance. As current treatment for paracoccidioidomycosis mainly uses azole derivatives, the presence of these genes can be postulated to play a similar role in P. brasiliensis, warning us for the possibility of resistant isolate emergence.
Costa
Christiane da Silva
Cda S
Laboratório de Biologia Molecular, CEL, IB, Universidade de Brasília, 70910-900 Brasília, DF, Brazil.
Albuquerque
Flávia Caixeta
FC
Andrade
Rosângela Vieira
RV
Oliveira
Gina Camilo de
GC
Almeida
Mauro Fernandes de
MF
Brigido
Marcelo de Macedo
Mde M
Maranhão
Andrea Queiroz
AQ
D018528:ATP-Binding Cassette Transporters / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D000935:Antifungal Agents / Q000494:pharmacology*; D026141:Drug Resistance, Multiple, Fungal / Q000235:genetics* / Q000502:physiology; D020224:Expressed Sequence Tags / Q000378:metabolism*; D006801:Humans; D026901:Membrane Transport Proteins / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D010228:Paracoccidioides / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D018528:ATP-Binding Cassette Transporters; D000935:Antifungal Agents; D026901:Membrane Transport Proteins