Exploring the resistance mechanisms in Trichosporon asahii: Triazoles as the last defense for invasive trichosporonosis.
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| Abstract |
Trichosporon asahii has recently been recognized as an emergent fungal pathogen able to cause invasive infections in neutropenic cancer patients as well as in critically ill patients submitted to invasive medical procedures and broad-spectrum antibiotic therapy. T. asahii is the main pathogen associated with invasive trichosporonosis worldwide. Treatment of patients with invasive trichosporonosis remains a controversial issue, but triazoles are mentioned by most authors as the best first-line antifungal therapy. There is mounting evidence supporting the claim that fluconazole (FLC) resistance in T. asahii is emerging worldwide. Since 2000, 15 publications involving large collections of T. asahii isolates described non-wild type isolates for FLC and/or voriconazole. However, very few papers have addressed the epidemiology and molecular mechanism of antifungal resistance in Trichosporon spp. Data available suggest that continuous exposure to azoles can induce mutations in the ERG11 gene, resulting in resistance to this class of antifungal drugs. A recent report characterizing T. asahii azole-resistant strains found several genes differentially expressed and highly mutated, including genes related to the Target of Rapamycin (TOR) pathway, indicating that evolutionary modifications on this pathway induced by FLC stress may be involved in developing azole resistance. Finally, we provided new data suggesting that hyperactive efflux pumps may play a role as drug transporters in FLC resistant T. asahii strains.
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| Authors | Ana Carolina Barbosa Padovan, Walicyranison Plinio da Silva Rocha, Ana Caroline de Moraes Toti, Daniel Felipe Freitas de Jesus, Guilherme Maranhão Chaves, Arnaldo Lopes Colombo |
| Journal | Fungal genetics and biology : FG & B (Fungal Genet Biol) Vol. 133 Pg. 103267 (12 2019) ISSN: 1096-0937 [Electronic] United States |
| PMID | 31513917 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review) |
| Copyright | Copyright © 2019 Elsevier Inc. All rights reserved. |
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