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- Name help_outline itraconazole Identifier CHEBI:6076 (CAS: 84625-61-6) help_outline Charge 0 Formula C35H38Cl2N8O4 InChIKeyhelp_outline VHVPQPYKVGDNFY-ZPGVKDDISA-N SMILEShelp_outline CCC(C)n1ncn(-c2ccc(cc2)N2CCN(CC2)c2ccc(OC[C@H]3CO[C@@](Cn4cncn4)(O3)c3ccc(Cl)cc3Cl)cc2)c1=O 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline ATP Identifier CHEBI:30616 (Beilstein: 3581767) help_outline Charge -4 Formula C10H12N5O13P3 InChIKeyhelp_outline ZKHQWZAMYRWXGA-KQYNXXCUSA-J SMILEShelp_outline Nc1ncnc2n(cnc12)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1,284 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H2O Identifier CHEBI:15377 (CAS: 7732-18-5) help_outline Charge 0 Formula H2O InChIKeyhelp_outline XLYOFNOQVPJJNP-UHFFFAOYSA-N SMILEShelp_outline [H]O[H] 2D coordinates Mol file for the small molecule Search links Involved in 6,264 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline ADP Identifier CHEBI:456216 (Beilstein: 3783669) help_outline Charge -3 Formula C10H12N5O10P2 InChIKeyhelp_outline XTWYTFMLZFPYCI-KQYNXXCUSA-K SMILEShelp_outline Nc1ncnc2n(cnc12)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 841 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline phosphate Identifier CHEBI:43474 Charge -2 Formula HO4P InChIKeyhelp_outline NBIIXXVUZAFLBC-UHFFFAOYSA-L SMILEShelp_outline OP([O-])([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 1,002 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,521 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:33503 | RHEA:33504 | RHEA:33505 | RHEA:33506 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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| Gene Ontology help_outline |
Publications
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Trichophyton rubrum azole resistance mediated by a new ABC transporter, TruMDR3.
Monod M., Feuermann M., Salamin K., Fratti M., Makino M., Alshahni M.M., Makimura K., Yamada T.
The mechanisms of terbinafine resistance in a set of clinical isolates of <i>Trichophyton rubrum</i> have been studied recently. Of these isolates, TIMM20092 also showed reduced sensitivity to azoles. The azole resistance of TIMM20092 could be inhibited by milbemycin oxime, prompting us to examine ... >> More
The mechanisms of terbinafine resistance in a set of clinical isolates of <i>Trichophyton rubrum</i> have been studied recently. Of these isolates, TIMM20092 also showed reduced sensitivity to azoles. The azole resistance of TIMM20092 could be inhibited by milbemycin oxime, prompting us to examine the potential of <i>T. rubrum</i> to develop resistance through multidrug efflux transporters. The introduction of a <i>T. rubrum</i> cDNA library into <i>Saccharomyces cerevisiae</i> allowed the isolation of one transporter of the major facilitator superfamily (MFS) conferring resistance to azoles (TruMFS1). To identify more azole efflux pumps among 39 ABC and 170 MFS transporters present within the <i>T. rubrum</i> genome, we performed a BLASTp analysis of <i>Aspergillus fumigatus</i>, <i>Candida albicans</i>, and <i>Candida glabrata</i> on transporters that were previously shown to confer azole resistance. The identified candidates were further tested by heterologous gene expression in <i>S. cerevisiae</i> Four ABC transporters (TruMDR1, TruMDR2, TruMDR3, and TruMDR5) and a second MFS transporter (TruMFS2) proved to be able to operate as azole efflux pumps. Milbemycin oxime inhibited only TruMDR3. Expression analysis showed that both <i>TruMDR3</i> and <i>TruMDR2</i> were significantly upregulated in TIMM20092. TruMDR3 transports voriconazole (VRC) and itraconazole (ITC), while TruMDR2 transports only ITC. Disruption of <i>TruMDR3</i> in TIMM20092 abolished its resistance to VRC and reduced its resistance to ITC. Our study highlights TruMDR3, a newly identified transporter of the ABC family in <i>T. rubrum</i>, which can confer azole resistance if overexpressed. Finally, inhibition of TruMDR3 by milbemycin suggests that milbemycin analogs could be interesting compounds to treat dermatophyte infections in cases of azole resistance. << Less
Antimicrob. Agents Chemother. 0:0-0(2019) [PubMed] [EuropePMC]
This publication is cited by 7 other entries.