烟曲霉β-1,3-葡聚糖合成酶在分子调控及真菌感染中的作用

摘要/Abstract

摘要：

烟曲霉是最为常见的重要病原真菌之一，可引起侵袭性曲霉病、变应性支气管肺曲霉病、曲霉肿以及严重过敏性哮喘等多种疾病，病死率高。β-1，3-葡聚糖是烟曲霉细胞壁的主要骨架成份，也是重要免疫原性因子，由β-1，3-葡聚糖合成酶催化生成，该酶主要由催化亚基Fks蛋白和调节亚基Rho1蛋白组成，Rho1可利用自身活性状态转化和修饰调控β-1，3-葡聚糖的合成，也可能通过控制肌动蛋白骨架重排影响Fks胞内转位和功能。该文对β-1，3-葡聚糖的合成的分子调控机制与烟曲霉及其他病原真菌感染进行综述。

关键词: 烟曲霉, β-1,3-葡聚糖, 天然免疫应答, Rho蛋白

Abstract:

As a major pathogenic fungus,Aspergillus fumigatus is able to cause the invasive pulmonary aspergilosis with high mortality,or chronic infection and allergic disease.β-1,3-glucan is not only the back-bone of cell wall of A.fumigatus,but also an essential immunogenic factor.β-1,3-glucan synthase is composed of a catalytic subunit,Fks and regulatory subunit,Rho1.Rho1 can bind to Fks and regulate the synthesis of β-1,3-glucan through the transformation and modification of its active state.It also may affect cellular translocation and function of Fks by controlling the actin cytoskeleton rearrangement.

Key words: Aspergillus fumigatus, β-1,3-glucan, innate immune response, Rho-GTPase

中图分类号:

R379.6

张曦, 韩黎. 烟曲霉β-1,3-葡聚糖合成酶在分子调控及真菌感染中的作用[J]. 中国真菌学杂志, 2017, 12(5): 309-311,317.

ZHANG Xi, HAN Li. Molecular regulation on biosynthesis of β-1,3-glucan on cell wall of Aspergillus fumigatus[J]. Chinese Journal of Mycology, 2017, 12(5): 309-311,317.

参考文献

[1] Chen J,Wang F,Zheng S,et al.Pavement cells:a model system for non-transcriptional auxin signalling and crosstalks[J].J Exp Bot,2015,66(16):4957-4970.
[2] Haddadi P,Ma L,Wang H,et al.Genome-wide transcriptome analyses provides insights into the lifestyle transition and effector repertoire of Leptosphaeria maculans during colonization of B.napus seedlings[J].Mol Plant Pathol,2016,17(8):1196-1210.
[3] van der Meer JW,Joosten LA,Riksen N,et al.Trained immunity:A smart way to enhance innate immune defence[J].Mol Immunol,2015,68(1):40-44.
[4] Latge JP.The cell wall:a carbohydrate armour for the fungal cell[J].Mol Microbiol,2007,66(2):279-290.
[5] Perlin DS.Echinocandin resistance,susceptibility testing and prophylaxis:implications for patient management[J].Drugs,2014,74(14):1573-1585.
[6] Valiante V,Macheleidt J,Foge M,et al.The Aspergillus fumigatus cell wall integrity signaling pathway:drug target,compensatory pathways,and virulence[J].Front Microbiol,2015,4(6):325.
[7] Ishihara S,Hirata A,Nogami S,et al.Homologous subunits of 1,3-beta-glucan synthase are important for spore wall assembly in Saccharomyces cerevisiae[J].Eukaryot Cell,2007,6(2):143-156.
[8] Beauvais A,Bruneau JM,Mol PC,et al.Glucan synthase complex of Aspergillus fumigatus[J].J Bacteriol,2001,183(7):2273-2279.
[9] Periasamy A,Shadiac N,Amalraj A,et al.Cell-free protein synthesis of membrane (1,3)-β-d-glucan (curdlan) synthase:co-translational insertion in liposomes and reconstitution in nanodiscs[J].Biochim Biophys Acta,2013,1828(2):743-757.
[10] Rocha EM,Garcia-Effron G,Park S,et al.A Ser678Pro substitution in Fks1p confers resistance to echinocandin drugs in Aspergillus fumigatus[J].Antimicrob Agents Chemother,2007,51(11):4174-4176.
[11] Caballero-Lima D,Kaneva IN,Watton SP,et al.The spatial distribution of the exocyst and actin cortical patches is sufficient to organize hyphal tip growth[J].Eukaryot Cell,2013,12(7):998-1008.
[12] Delley PA,Hall MN.Cell wall stress depolarizes cell growth via hyperactivation of RHO1[J].J Cell Biol,1999,147(1):163-174.
[13] Zhang C,Cheng J,Jiang Y,et al.Application of caspofungin in China compared with amphotericin B and fluconazole[J].Ther Clin Risk Manag,2014,9(10):737-741.
[14] Tajadura V,Garcia B,Garcia I,et al.Schizosaccharomyces pombe Rgf3p is a specific Rho1 GEF that regulates cell wall beta-glucan biosynthesis through the GTPase Rho1p[J].J Cell Sci,2004,117(Pt25):6163-6174.
[15] Fitch PG,Gammie AE,Lee DJ,et al.Lrg1p Is a Rho1 GTPase-activating protein required for efficient cell fusion in yeast[J].Genetics,2004,168(2):733-746.
[16] Inoue SB,Qadota H,Arisawa M,et al.Prenylation of Rho1p is required for activation of yeast 1,3-beta-glucan synthase[J].J Biol Chem,1999,274(53):38119-38124.
[17] Bickle M,Delley PA,Schmidt A,et al.Cell wall integrity modulates RHO1 activity via the exchange factor ROM2[J].EMBO J,1998,17(8):2235-2245.
[18] Utsugi T,Minemura M,Hirata A,et al.Movement of yeast 1,3-beta-glucan synthase is essential for uniform cell wall synthesis[J].Genes Cells,2002,7(1):1-9.
[19] Hartmann S,Ridley AJ,Lutz S.The Function of Rho-Associated Kinases ROCK1 and ROCK2 in the Pathogenesis of Cardiovascular Disease[J].Front Pharmacol,2015,11(6):276.
[20] Chen Q,Pollard TD.Actin filament severing by cofilin dismantles actin patches and produces mother filaments for new patches[J].Curr Biol,2013,23(13):1154-1162.
[21] Curwin AJ,von Blume J,Malhotra V.Cofilin-mediated sorting and export of specific cargo from the Golgi apparatus in yeast[J].Mol Biol Cell,2012,23(12):2327-2338.
[22] Han L,Stope MB,de Jesus ML,et al.Direct stimulation of receptor-controlled phospholipase D1 by phospho-cofilin[J].EMBO J,2007,26(19):4189-4202.
[23] Zambuzzi-Carvalho PF,Fernandes AG,Valadares MC,et al.Transcriptional profile of the human pathogenic fungus Paracoccidioides lutzii in response to sulfamethoxazole[J].Med Mycol,2015,53(5):477-492.
[24] Harkins AL,Yuan G,London SD,et al.An oleate-stimulated,phosphatidylinositol 4,5-bisphosphate-independent phospholipase D in Schizosaccharomyces pombe[J].FEMS Yeast Res,2010,10(6):717-726.
[25] Dolan JW,Bell AC,Hube B,et al.Candida albicans PLD I activity is required for full virulence[J].Med Mycol,2004,42(5):439-447.
[26] Ko YT,Frost DJ,Ho CT,et al.Inhibition of yeast (1,3)-beta-glucan synthase by phospholipase A2 and its reaction products[J].Biochim Biophys Acta,1994,1193(1):31-40.
[27] De Pascale G,Tumbarello M.Fungal infections in the ICU:advances in treatment and diagnosis[J].Curr Opin Crit Care,2015,21(5):421-429.
[28] Dichtl K,Samantaray S,Aimanianda V,et al.Aspergillus fumigatus devoid of cell wall β-1,3-glucan is viable,massively sheds galactomannan and is killed by septum formation inhibitors[J].Mol Microbiol,2015,95(3):458-471.
[29] Schlosser A,Thomsen T,Moeller JB,et al.Characterization of FIBCD1 as an acetyl group-binding receptor that binds chitin[J].J Immunol,2009,183(6):3800-3809.
[30] Aranda-Martinez A,Lopez-Moya F,Lopez-Llorca LV.Cell wall composition plays a key role on sensitivity of filamentous fungi to chitosan[J].J Basic Microbiol,2016,56(10):1059-1070.
[31] Marcoszambrano,LJ,Gómezperosanz M,Escribano P,et al.Biofilm production and antibiofilm activity of echinocandins and liposomal amphotericin b in echinocandin-resistant yeast species[J].Antimicrob Agents Chemother,2016,60(6):3579-3586.