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1
Cryptococcus neoformans isolates from transplant recipients are not selected for resistance to calcineurin inhibitors by current immunosuppressive regimens.目前的免疫抑制方案并未筛选出对移植受者的新型隐球菌分离株具有钙调神经磷酸酶抑制剂抗性的菌株。
J Clin Microbiol. 2005 Jan;43(1):464-7. doi: 10.1128/JCM.43.1.464-467.2005.
2
Calcineurin inhibitor agents interact synergistically with antifungal agents in vitro against Cryptococcus neoformans isolates: correlation with outcome in solid organ transplant recipients with cryptococcosis.钙调神经磷酸酶抑制剂药物在体外与抗真菌药物协同作用，对抗新型隐球菌分离株：与实体器官移植受者隐球菌病的预后相关性。
Antimicrob Agents Chemother. 2008 Feb;52(2):735-8. doi: 10.1128/AAC.00990-07. Epub 2007 Dec 10.
3
and Assessment of FK506 Analogs as Novel Antifungal Drug Candidates.并评估 FK506 类似物作为新型抗真菌药物候选物。
Antimicrob Agents Chemother. 2018 Oct 24;62(11). doi: 10.1128/AAC.01627-18. Print 2018 Nov.
4
Cryptococcus neoformans in organ transplant recipients: impact of calcineurin-inhibitor agents on mortality.器官移植受者中的新型隐球菌：钙调神经磷酸酶抑制剂对死亡率的影响。
J Infect Dis. 2007 Mar 1;195(5):756-64. doi: 10.1086/511438. Epub 2007 Jan 23.
5
Synergistic antifungal activities of bafilomycin A(1), fluconazole, and the pneumocandin MK-0991/caspofungin acetate (L-743,873) with calcineurin inhibitors FK506 and L-685,818 against Cryptococcus neoformans.巴弗洛霉素A（1）、氟康唑以及棘白菌素MK-0991/醋酸卡泊芬净（L-743,873）与钙调神经磷酸酶抑制剂FK506和L-685,818对新型隐球菌的协同抗真菌活性。
Antimicrob Agents Chemother. 2000 Mar;44(3):739-46. doi: 10.1128/AAC.44.3.739-746.2000.
6
Immunosuppressive and nonimmunosuppressive cyclosporine analogs are toxic to the opportunistic fungal pathogen Cryptococcus neoformans via cyclophilin-dependent inhibition of calcineurin.免疫抑制性和非免疫抑制性环孢素类似物通过亲环蛋白依赖性抑制钙调神经磷酸酶，对机会性真菌病原体新型隐球菌具有毒性。
Antimicrob Agents Chemother. 2000 Jan;44(1):143-9. doi: 10.1128/AAC.44.1.143-149.2000.
7
The immunosuppressant FK506 and its nonimmunosuppressive analog L-685,818 are toxic to Cryptococcus neoformans by inhibition of a common target protein.免疫抑制剂FK506及其非免疫抑制类似物L-685,818通过抑制一种共同的靶蛋白对新型隐球菌有毒性作用。
Antimicrob Agents Chemother. 1997 Jan;41(1):156-61. doi: 10.1128/AAC.41.1.156.
8
Immunotherapy with tacrolimus (FK506) does not select for resistance to calcineurin inhibitors in Candida albicans isolates from liver transplant patients.使用他克莫司（FK506）进行免疫治疗不会在肝移植患者的白色念珠菌分离株中选择对钙调神经磷酸酶抑制剂产生耐药性。
Antimicrob Agents Chemother. 2006 Apr;50(4):1573-7. doi: 10.1128/AAC.50.4.1573-1577.2006.
9
ATP-binding cassette transporters and calcineurin inhibitors: potential clinical implications.ATP结合盒转运蛋白与钙调神经磷酸酶抑制剂：潜在的临床意义。
Transplant Proc. 2001 May;33(3):2420-1. doi: 10.1016/s0041-1345(01)02059-0.
10
Structure-Guided Synthesis of FK506 and FK520 Analogs with Increased Selectivity Exhibit Therapeutic Efficacy against Cryptococcus.结构导向的 FK506 和 FK520 类似物的合成，提高了选择性，对隐球菌表现出治疗效果。
mBio. 2022 Jun 28;13(3):e0104922. doi: 10.1128/mbio.01049-22. Epub 2022 May 23.

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Antifungal adjuvants: Preserving and extending the antifungal arsenal.抗真菌佐剂：保存并扩充抗真菌武器库。
Virulence. 2017 Feb 17;8(2):198-210. doi: 10.1080/21505594.2016.1216283. Epub 2016 Jul 26.
2
Genetic and genomic architecture of the evolution of resistance to antifungal drug combinations.抗真菌药物组合耐药性进化的遗传和基因组结构。
PLoS Genet. 2013 Apr;9(4):e1003390. doi: 10.1371/journal.pgen.1003390. Epub 2013 Apr 4.
3
Regulatory circuitry governing fungal development, drug resistance, and disease.调控真菌发育、耐药性和疾病的调控回路。
Microbiol Mol Biol Rev. 2011 Jun;75(2):213-67. doi: 10.1128/MMBR.00045-10.
4
Genome variation in Cryptococcus gattii, an emerging pathogen of immunocompetent hosts.新型隐球菌（Cryptococcus gattii）的基因组变异，这种病原体能感染免疫功能正常的宿主。
mBio. 2011 Feb 8;2(1):e00342-10. doi: 10.1128/mBio.00342-10. Print 2011.
5
Emergence and pathogenicity of highly virulent Cryptococcus gattii genotypes in the northwest United States.美国西北部高毒力隐球菌荚膜基因型的出现和致病性。
PLoS Pathog. 2010 Apr 22;6(4):e1000850. doi: 10.1371/journal.ppat.1000850.
6
First reported case of Cryptococcus gattii in the Southeastern USA: implications for travel-associated acquisition of an emerging pathogen.美国东南部首例加氏隐球菌病例：新兴病原体与旅行相关感染的影响。
PLoS One. 2009 Jun 10;4(6):e5851. doi: 10.1371/journal.pone.0005851.
7
Cryptococcosis in solid organ transplant recipients: current state of the science.实体器官移植受者的隐球菌病：科学现状
Clin Infect Dis. 2008 Nov 15;47(10):1321-7. doi: 10.1086/592690.
8
Role of a CUF1/CTR4 copper regulatory axis in the virulence of Cryptococcus neoformans.CUF1/CTR4铜调节轴在新型隐球菌毒力中的作用
J Clin Invest. 2007 Mar;117(3):794-802. doi: 10.1172/JCI30006. Epub 2007 Feb 8.

本文引用的文献

1
Adenylyl cyclase-associated protein Aca1 regulates virulence and differentiation of Cryptococcus neoformans via the cyclic AMP-protein kinase A cascade.腺苷酸环化酶相关蛋白Aca1通过环磷酸腺苷-蛋白激酶A级联反应调节新型隐球菌的毒力和分化。
Eukaryot Cell. 2004 Dec;3(6):1476-91. doi: 10.1128/EC.3.6.1476-1491.2004.
2
Antifungal attributes of immunosuppressive agents: new paradigms in management and elucidating the pathophysiologic basis of opportunistic mycoses in organ transplant recipients.免疫抑制剂的抗真菌特性：器官移植受者机会性真菌病管理的新范式及阐明其病理生理基础
Transplantation. 2004 Mar 27;77(6):795-800. doi: 10.1097/01.tp.0000117252.75651.d6.
3
Phospholipid-binding protein Cts1 controls septation and functions coordinately with calcineurin in Cryptococcus neoformans.磷脂结合蛋白Cts1控制新生隐球菌的隔膜形成，并与钙调神经磷酸酶协同发挥作用。
Eukaryot Cell. 2003 Oct;2(5):1025-35. doi: 10.1128/EC.2.5.1025-1035.2003.
4
Effect of degree of encapsulation upon virulence of Cryptococcus neoformans.包囊化程度对新型隐球菌毒力的影响。
Proc Soc Exp Biol Med. 1959 Aug-Sep;101:773-7. doi: 10.3181/00379727-101-25090.
5
Teaching old drugs new tricks: reincarnating immunosuppressants as antifungal drugs.让老药有新用：将免疫抑制剂变身抗真菌药物。
Curr Opin Investig Drugs. 2003 Feb;4(2):192-9.
6
Infections of the central nervous system in transplant recipients.移植受者的中枢神经系统感染
Transpl Infect Dis. 2000 Sep;2(3):101-11. doi: 10.1034/j.1399-3062.2000.020302.x.
7
Cryptococcus neoformans infection in organ transplant recipients: variables influencing clinical characteristics and outcome.器官移植受者中的新型隐球菌感染：影响临床特征及预后的变量
Emerg Infect Dis. 2001 May-Jun;7(3):375-81. doi: 10.3201/eid0703.010302.
8
Calcineurin regulatory subunit is essential for virulence and mediates interactions with FKBP12-FK506 in Cryptococcus neoformans.钙调神经磷酸酶调节亚基对新型隐球菌的毒力至关重要，并介导其与FKBP12-FK506的相互作用。
Mol Microbiol. 2001 Feb;39(4):835-49. doi: 10.1046/j.1365-2958.2001.02295.x.
9
Pathogenic roles for fungal melanins.真菌黑色素的致病作用。
Clin Microbiol Rev. 2000 Oct;13(4):708-17. doi: 10.1128/CMR.13.4.708.
10
RAS1 regulates filamentation, mating and growth at high temperature of Cryptococcus neoformans.RAS1调节新型隐球菌在高温下的丝状化、交配和生长。
Mol Microbiol. 2000 Apr;36(2):352-65. doi: 10.1046/j.1365-2958.2000.01852.x.

目前的免疫抑制方案并未筛选出对移植受者的新型隐球菌分离株具有钙调神经磷酸酶抑制剂抗性的菌株。

Cryptococcus neoformans isolates from transplant recipients are not selected for resistance to calcineurin inhibitors by current immunosuppressive regimens.

作者信息

Blankenship Jill R, Singh Nina, Alexander Barbara D, Heitman Joseph

机构信息

Department of Molecular Genetics and Microbiology, 322 CARL Building, Box 3546, Duke University Medical Center, Research Drive, Durham, NC 27710, USA.

出版信息

J Clin Microbiol. 2005 Jan;43(1):464-7. doi: 10.1128/JCM.43.1.464-467.2005.

DOI:10.1128/JCM.43.1.464-467.2005
PMID:15635017
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC540157/
Abstract

The immunosuppressants tacrolimus (FK506) and cyclosporine A inhibit calcineurin and have potent antifungal activity. In this study, 24% of Cryptococcus neoformans isolates from solid-organ transplant patients exhibited altered sensitivity to these drugs, which may have an impact on the infectious course but does not appear to be the consequence of immunosuppressive therapy.

摘要

免疫抑制剂他克莫司（FK506）和环孢素A可抑制钙调神经磷酸酶，并具有强大的抗真菌活性。在本研究中，实体器官移植患者分离出的新型隐球菌菌株中有24%对这些药物的敏感性发生了改变，这可能会对感染病程产生影响，但似乎并非免疫抑制治疗的结果。