遗传 ›› 2011, Vol. 33 ›› Issue (10): 1048-1056.doi: 10.3724/SP.J.1005.2011.01048
王倩, 崔志峰
收稿日期:
2011-04-08
修回日期:
2011-07-25
出版日期:
2011-10-20
发布日期:
2011-10-25
通讯作者:
崔志峰
E-mail:zfcui@zjut.edu.cn
基金资助:
国家重点基础研究发展计划项目(973计划)资助(编号:2010CB126100)
WANG Qian, CUI Zhi-Feng
Received:
2011-04-08
Revised:
2011-07-25
Online:
2011-10-20
Published:
2011-10-25
摘要: 真菌的多向耐药性ABC转运蛋白(ATP-binding cassette transporters)是导致多药耐药性和抗真菌药物治疗效果明显下降的主要原因。文章对酿酒酵母(Saccharomyces cerevisiae)和主要致病真菌白色假丝酵母(Candida albicans)、新型隐球酵母(Cryptococcus neoformans)和烟曲霉(Aspergillus fumigatus)中的多向耐药性ABC转运蛋白的种类、药物外排机制以及基因表达调控网络的研究进展作一综述, 为深入了解真菌的多向耐药性机制以及探讨克服多向耐药性的策略和提高药效提供参考。
王倩,崔志峰. 真菌的多向耐药性ABC转运蛋白[J]. 遗传, 2011, 33(10): 1048-1056.
WANG Qian, CUI Zhi-Feng. Pleiotropic drug resistance ABC transporters in fungi[J]. HEREDITAS, 2011, 33(10): 1048-1056.
[1] Cannon RD, Lamping E, Holmes AR, Niimi K, Baret PV, Keniya MV, Tanaba K, Niimi M, Goffeau A, Monk BC. Efflux-mediated antifungal drug resistance. Clin Microbiol Rev, 2009, 22(2): 291-321.[2] Bauer BE, Schüller C, Kuchler K. Inventory & Evolution of Fungal ABC Protein Genes. In: Holland IB, Coole S, Kuchler K, Higgins C, eds. ABC Proteins: From Bacteria to Man. London: Academic Press, Elsevier Science, 2003: 295-316.[3] Gaur M, Choudhury D, Prasad R. Complete inventory of ABC proteins in human pathogenic yeast, Candida albicans. J Mol Microbiol Biotechnol, 2005, 9(1): 3-15.[4] Jungwirth H, Kuchler K. Yeast ABC transporters-A tale of sex, stress, drugs and aging. FEBS Lett, 2006, 580(4): 1131-1138.[5] Morschhäuser J. Regulation of multidrug resistance in pathogenic fungi. Fungal Genet Biol, 2010, 47(2): 94-106.[6] Taglicht D, Michaelis S. Saccharomyces cerevisiae ABC proteins and their relevance to human health and disease. Methods Enzymol, 1998, 292: 130-162.[7] Lamping E, Baret PV, Holmes AR, Monk BC, Goffeau A, Cannon RD. Fungal PDR transporters: Phylogeny, topology, motifs and function. Fungal Genet Biol, 2010, 47(2): 127-142.[8] Goffeau A, Barrell BG, Bussey H, Davis RW, Dujon B, Feldmann H, Galibert F, Hoheisel JD, Jacq C, Johnston M, Louis EJ, Mewes HW, Murakami Y, Philippsen P, Tettelin H, Oliver SG. Life with 6000 genes. Science, 1996, 274(5287): 546-567.[9] Decottignies A, Goffeau A. Complete inventory of the yeast ABC proteins. Nat Genet, 1997, 15(2): 137-145.[10] Balzi E, Wang M, Leterme S, van Dyck L, Goffeau A. PDR5: a novel yeast multidrug resistance conferring transporter controlled by the transcription regulator PDR1. J Biol Chem, 1994, 269(3): 2206-2214.[11] Bissinger PH, Kuchler K. Molecular cloning and expression of the Saccharomyces cerevisiae STS1 gene product. A yeast ABC transporter conferring mycotoxin resistance. J Biol Chem, 1994, 269(6): 4180-4186.[12] Hirata D, Yano K, Miyahara K, Miyakawa T. Saccharomyces cerevisiae YDR1, which encodes a member of the ATP-binding cassette (ABC) superfamily, is required for multidrug resistance. Curr Genet, 1994, 26(4): 285-294.[13] Kolaczkowski M, van der Rest M, Cybularz-Kolaczkowski A, Soumillion JP, Konings WN, Goffeau A. Anticancer drugs, ionophoric peptides, and steroids as substrates of the yeast multidrug transporter Pdr5p. J Biol Chem, 1996, 271(49): 31543-31548.[14] Miyahara K, Mizunuma M, Hirata D, Tsuchiya E, Miyakawa T. The involvement of the Saccharomyces cerevisiae multidrug resistance transporters Pdr5p and Snq2p in cation resistance. FEBS Lett, 1996, 399(3): 317-320.[15] Katzmann DJ, Burnett PE, Golin J, Mahé Y, Moye-Rowley WS. Transcriptional control of the yeast PDR5 gene by the PDR3 gene product. Mol Cell Biol, 1994, 14(7): 4653-4661.[16] Hellauer K, Akache B, MacPherson S, Sirard E, Turcotte B. Zinc cluster protein Rdr1p is a transcriptional repressor of the PDR5 gene encoding a multidrug transporter. J Biol Chem, 2002, 277(20): 17671-17676.[17] Miyahara K, Hirata D, Miyakawa T. yAP-1- and yAP-2-mediated, heat shock-induced transcriptional activation of the multidrug resistance ABC transporter genes in Saccharomyces cerevisiae. Curr Genet, 1996, 29(2): 103-105.[18] Servos J, Haase E, Brendel M. Gene SNQ2 of Saccharomyces cerevisiae, which confers resistance to 4-nitro-quinoline-N-oxide and other chemicals, encodes a 169 kDa protein homologous to ATP-dependent permeases. Mol Gen Genet, 1993, 236(2-3): 214-218.[19] Decottignies A, Lambert L, Catty P, Degand H, Epping EA, Moye-Rowley WS, Balzi E, Goffeau A. Identification and characterization of SNQ2, a new multidrug ATP binding cassette transporter of the yeast plasma membrane. J Biol Chem, 1995, 270(30): 18150-18157.[20] Mahé Y, Parle-McDermott A, Nourani A, Delahodde A, Lamprecht A, Kuchler K. The ATP-binding cassette multidrug transporter Snq2 of Saccharomyces cerevisiae: a novel target for the transcription factors Pdr1 and Pdr3. Mol Microbiol, 1996, 20(1): 109-117.[21] Cui ZF, Shiraki T, Hirata D, Miyakawa T. Yeast gene YRR1, which is required for resistance to 4-nitroquinoline N-oxide, mediates transcriptional activation of the multidrug resistance transporter gene SNQ2. Mol Microbiol, 1998, 29(5): 1307-1315.[22] Le Crom S, Devaux F, Marc P, Zhang XT, Moye-Rowley WS, Jacq C. New insights into the pleiotropic drug resistance network from genome-wide characterization of the YRR1 transcription factor regulation system. Mol Cell Biol, 2002, 22(8): 2642-2649.[23] Kolaczkowska A, Kolaczkowska M, Goffeau A, Moye-Rowley WS. Compensatory activation of the multidrug transporters Pdr5p, Snq2p, and Yor1p by Pdr1p in Saccharomyces cerevisiae. FEBS Lett, 2008, 582(6): 977-983.[24] Wolfger H, Mahe Y, Parle-McDermott A, Delahodde A, Kuchler K. The yeast ATP binding cassette (ABC) protein genes PDR10 and PDR15 are novel targets for the Pdr1 and Pdr3 transcriptional regulators. FEBS Lett, 1997, 418(3): 269-274.[25] Wolfger H, Mamnun YM, Kuchler K. The yeast Pdr15p ATP-binding cassette (ABC) protein is a general stress response factor implicated in cellular detoxification. J Biol Chem, 2004, 279(12): 11593-11599.[26] Rockwell NC, Wolfger H, Kuchler K, Thorner J. ABC trans-porter Pdr10 regulates the membrane microenvironment of Pdr12 in Saccharomyces cerevisiae. J Membrane Biol, 2009, 229(1): 27-52.[27] Piper P, Mahé Y, Thompson S, Pandjaitan R, Holyoak C, Egner R, Mühlbauer M, Coote P, Kuchler K. The Pdr12 ABC transporter is required for the development of weak organic acid resistance in yeast. EMBO J, 1998, 17(15): 4257-4265.[28] Kren A, Mamnun YM, Bauer BE, Schüller C, Wolfger H, Hatzixanthis K, Mollapour M, Gregori C, Piper P, Kuchler K. War1p, a novel transcription factor controlling weak acid stress response in yeast. Mol Cell Biol, 2003, 23(5): 1775-1785.[29] Wilcox LJ, Balderes DA, Wharton B, Tinkelenberg AH, Rao G, Sturley SL. Transcriptional profiling identifies two members of the ATP-binding cassette transporter superfamily required for sterol uptake in yeast. J Biol Chem, 2002, 277(36): 32466-32472.[30] Kohut P, Wüstner D, Hronska L, Kuchler K, Hapala I, Vala-chovic M. The role of ABC proteins Aus1p and Pdr11p in the uptake of external sterols in yeast: Dehydroergosterol fluo rescence study. Biochem Biophys Res Commun, 2011, 404(1): 233-238.[31] Kuchler K, Sterne RE, Thorner J. Saccharomyces cerevisiae STE6 gene product: a novel pathway for protein export in eukaryotic cells. EMBO J, 1989, 8(13): 3973-3984.[32] Katzmann DJ, Hallstrom TC, Voet M, Wysock W, Golin J, Volckaert G, Moye-Rowley WS. Expression of an ATP-binding cassette transporter-encoding gene (YOR1) is required for oligomycin resistance in Saccharomyces cerevisiae. Mol Cell Biol, 1995, 15(12): 6875-6883.[33] Cui Z, Hirata D, Tsuchiya E, Osada H, Miyakawa T. The multidrug resistance-associated protein (MRP) subfamily (Yrs1/Yor1) of Saccharomyces cerevisiae is important for the tolerance to a broad range of organic anions. J Biol Chem, 1996, 271(25): 14712-14716.[34] Katzmann DJ, Epping EA, Moye-Rowley WS. Mutational disruption of plasma membrane trafficking of Saccharomyces cerevisiae Yor1p, a homologue of mammalian multidrug resistance protein. Mol Cell Biol, 1999, 19(4): 2998-3009.[35] Zhang XT, Cui ZF, Miyakawa T, Moye-Rowley WS. Cross-talk between transcriptional regulators of multidrug resistance in Saccharomyces cerevisiae. J Biol Chem, 2001, 276(12): 8812-8819.[36] Szczypka MS, Wemmie JA, Moye-Rowley WS Thiele DJ. A yeast metal resistance protein similar to human cystic fibrosis transmembrane conductance regulator (CFTR) and multidrug resistance-associated protein. J Biol Chem, 1994, 269(36): 22853-22857.[37] Li ZS, Szczypka M, Lu YP, Thiele DJ, Rea PA. The yeast cadmium factor protein (YCF1) is a vacuolar glutathione S-conjugate pump. J Biol Chem, 1996, 271(11): 6509-6517.[38] Sharma KG, Mason DL, Liu GS, Rea PA, Bachhawat AK, Michaelis S. Localization, regulation, and substrate transport properties of Bpt1p, a Saccharomyces cerevisiae MRP-type ABC transporter. Eukaryot Cell, 2002, 1(3): 391-400.[39] Ortiz DF, St Pierre MV, Abdulmessih A, Arias IM. A yeast ATP-binding cassette-type protein mediating ATP-dependent bile acid transport. J Biol Chem, 1997, 272(24): 15358-15365.[40] Balzi E, Chen W, Ulaszewski S, Capieaux E, Goffeau A. The multidrug resistance gene PDR1 from Saccharomyces cerevisiae. J Biol Chem, 1987, 262(35): 16871-16879.[41] Delaveau T, Delahodde A, Carvajal E, Subik J, Jacq C. PDR3, a new yeast regulatory gene, is homologous to PDR1 and controls the multidrug resistance phenomenon. Mol Gen Genet, 1994, 244(5): 501-511.[42] Mamnun YM, Pandjaitan R, Mahé Y, Delahodde A, Kuchler K. The yeast zinc finger regulators Pdr1p and Pdr3p control pleiotropic drug resistance (PDR) as homo- and heterodimers in vivo. Mol Microbiol, 2002, 46(5): 1429-1440.[43] Delahodde A, Delaveau T, Jacq C. Positive autoregulation of the yeast transcription factor Pdr3p, which is involved in con-trol of drug resistance. Mol Cell Biol, 1995, 15(8): 4043- 4051.[44] Ben-Yaacov R, Knoller S, Caldwell GA, Becker JM, Koltin Y. Candida albicans gene encoding resistance to benomyl and methotrexate is a multidrug resistance gene. Antimicrob Agents Chemother, 1994, 38(4): 648-652.[45] Sanglard D, Kuchler K, Ischer F, Pagani JL, Monod M, Bille J. Mechanisms of resistance to azole antifungal agents in Candida albicans isolates from AIDS patients involve specific multidrug transporters. Antimicrob Agents Chemother, 1995, 39(11): 2378-2386.[46] Sanglard D, Ischer F, Monod M, Bille J. Susceptibilities of Candida albicans multidrug transporter mutants to various antifungal agents and other metabolic inhibitors. Antimicrob Agents Chemother, 1996, 40(10): 2300-2305.[47] Niimi M, Niimi K, Takano Y, Holmes AR, Fischer FJ, Uehara Y, Cannon RD. Regulated overexpression of CDR1 in Candida albicans confers multidrug resistance. J Antimicrob Chemother, 2004, 54(6): 999-1006.[48] Sanglard D, Ischer F, Monod M, Bille J. Cloning of Candida albicans genes conferring resistance to azole antifungal agents: characterization of CDR2, a new multidrug ABC transporter gene. Microbiology, 1997, 143 (Pt 2): 405-416.[49] Gauthier C, Weber S, Alarco AM, Alqawi O, Daoud R, Georges E, Raymond M. Functional similarities and differences between Candida albicans Cdr1p and Cdr2p transporters. Antimicrob Agents Chemother, 2003, 47(5): 1543-1554.[50] Talibi D, Raymond M. Isolation of a putative Candida albicans transcriptional regulator involved in pleiotropic drug resistance by functional complementation of a pdr1 pdr3 mutation in Saccharomyces cerevisiae. J Bacteriol, 1999, 181(1): 231-240.[51] Coste AT, Ramsdale M, Ischer F, Sanglard D. Divergent functions of three Candida albicans zinc-cluster transcription factors (CTA4, ASG1 and CTF1) complementing pleiotropic drug resistance in Saccharomyces cerevisiae. Microbiology, 2008, 154(Pt 5): 1491-1501.[52] Coste AT, Karababa M, Ischer F, Bille J, Sanglard D. TAC1, transcriptional activator of CDR genes, is a new transcription factor involved in the regulation of Candida albicans ABC transporters CDR1 and CDR2. Eukaryot Cell, 2004, 3(6): 1639-1652.[53] Coste A, Turner V, Ischer F, Morschhäuser J, Forche A, Selmecki A, Berman J, Bille J, Sanglard D. A mutation in Tac1p, a transcription factor regulating CDR1 and CDR2, is coupled with loss of heterozygosity at chromosome 5 to mediate antifungal resistance in Candida albicans. Genetics, 2006, 172(4): 2139-2156.[54] Chen CG, Yang YL, Shih HI, Su CL, Lo HJ. CaNdt80 is involved in drug resistance in Candida albicans by regulating CDR1. Antimicrob Agents Chemother, 2004, 48(12): 4505-4512.[55] Sellam A, Tebbji F, Nantel A. Role of Ndt80p in sterol metabolism regulation and azole resistance in Candida albicans. Eukaryot Cell, 2009, 8(8): 1174-1183.[56] Loftus BJ, Fung E, Roncaglia P, Rowley D, Amedeo P, Bruno D, Vamathevan J, Miranda M, Anderson IJ, Fraser JA, Allen JE, Bosdet IE, Brent MR, Chiu R, Doering TL, Hyman RW. The genome of the basidiomycetous yeast and human pathogen Cryptococcus neoformans. Science, 2005, 307(5713): 1321-1324.[57] Thornewell SJ, Peery RB, Skatrud PL. Cloning and characterization of CneMDR1: a Cryptococcus neoformans gene encoding a protein related to multidrug resistance proteins. Gene, 1997, 201(1-2): 21-29.[58] Posteraro B, Sanguinetti M, Sanglard D, La Sorda M, Boccia S, Romano L, Morace G, Fadda G. Identification and characterization of a Cryptococcus neoformans ATP binding cassette (ABC) transporter-encoding gene, CnAFR1, involved in the resistance to fluconazole. Mol Microbiol, 2003, 47(2): 357-371.[59] Nierman WC, Pain A, Anderson MJ, Wortman JR, Kim HS, Arroyo J, Berriman M, Abe K, Archer DB, Bermejo C, Bennett J, Bowyer P, Chen D, Collins M, Coulsen R, Denning DW. Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus. Nature, 2005, 438(7071): 1151-1156.[60] Tobin MB, Peery RB, Skatrud PL. Genes encoding multiple drug resistance-like proteins in Aspergillus fumigatus and Aspergillus flavus. Gene, 1997, 200(1-2): 11-23.[61] Slaven JW, Anderson MJ, Sanglard D, Dixon GK, Bille J, Roberts IS, Denning DW. Increased expression of a novel Aspergillus fumigatus ABC transporter gene, atrF, in the presence of itraconazole in an itraconazole resistant clinical isolate. Fungal Genet Biol, 2002, 36(3): 199-206.[62] da Silva Ferreira ME, Capellaro JL, dos Reis Marques E, Malavazi I, Perlin D, Park S, Anderson JB, Colombo AL, Arthington-Skaggs BA, Goldman MHS, Goldman GH. In vitro evolution of itraconazole resistance in Aspergillus fumigatus involves multiple mechanisms of resistance. Antimicrob Agents Chemother, 2004, 48(11): 4405-4413.[63] Nascimento AM, Goldman GH, Park S, Marras SAE, Delmas G, Oza U, Lolans K, Dudley MN, Mann PA, Perlin DS. Multiple resistance mechanisms among Aspergillus fumigatus mutants with high-level resistance to itraconazole. Antimicrob Agents Chemother, 2003, 47(5): 1719-1726.[64] Jain P, Akula I, Edlind T. Cyclic AMP signaling pathway modulates susceptibility of Candida species and Saccharomyces cerevisiae to antifungal azoles and other sterol biosynthesis inhibitors. Antimicrob Agents Chemother, 2003, 47(10): 3195-3201.[65] Bruno VM, Mitchell AP. Regulation of azole drug susceptibility by Candida albicans protein kinase CK2. Mol Microbiol, 2005, 56(2): 559-573. |
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