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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。

Immunotherapy with tacrolimus (FK506) does not select for resistance to calcineurin inhibitors in Candida albicans isolates from liver transplant patients.

作者信息

Reedy Jennifer L, Husain Shahid, Ison Michael, Pruett Timothy L, Singh Nina, 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

Antimicrob Agents Chemother. 2006 Apr;50(4):1573-7. doi: 10.1128/AAC.50.4.1573-1577.2006.

DOI:10.1128/AAC.50.4.1573-1577.2006
PMID:16569889
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1426937/
Abstract

In Candida albicans, calcineurin mediates tolerance to azole antifungal drugs, survival in serum, and virulence. In this study, we examined 24 Candida isolates from liver transplant recipients receiving a calcineurin inhibitor as a component of their immunosuppressive therapy. We were unable to detect a difference in susceptibility to calcineurin inhibitors in combination with fluconazole, serum, or calcium in these isolates.

摘要

在白色念珠菌中，钙调神经磷酸酶介导对唑类抗真菌药物的耐受性、在血清中的存活能力及毒力。在本研究中，我们检测了24株来自接受钙调神经磷酸酶抑制剂作为免疫抑制治疗一部分的肝移植受者的念珠菌分离株。我们未能在这些分离株中检测到钙调神经磷酸酶抑制剂与氟康唑、血清或钙联合使用时敏感性的差异。

相似文献

1
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.
2
Synergistic effect of calcineurin inhibitors and fluconazole against Candida albicans biofilms.钙调神经磷酸酶抑制剂与氟康唑对白色念珠菌生物膜的协同作用。
Antimicrob Agents Chemother. 2008 Mar;52(3):1127-32. doi: 10.1128/AAC.01397-07. Epub 2008 Jan 7.
3
The calcineurin target, Crz1, functions in azole tolerance but is not required for virulence of Candida albicans.钙调神经磷酸酶的靶点Crz1在唑类耐受性中发挥作用，但白色念珠菌的毒力并不需要它。
Infect Immun. 2004 Dec;72(12):7330-3. doi: 10.1128/IAI.72.12.7330-7333.2004.
4
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.
5
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.
6
Calcineurin A of Candida albicans: involvement in antifungal tolerance, cell morphogenesis and virulence.白色念珠菌的钙调神经磷酸酶A：参与抗真菌耐受性、细胞形态发生和毒力。
Mol Microbiol. 2003 May;48(4):959-76. doi: 10.1046/j.1365-2958.2003.03495.x.
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Calcineurin is essential for survival during membrane stress in Candida albicans.钙调神经磷酸酶对于白色念珠菌在膜应激期间的存活至关重要。
EMBO J. 2002 Feb 15;21(4):546-59. doi: 10.1093/emboj/21.4.546.
8
Calcineurin promotes infection of the cornea by Candida albicans and can be targeted to enhance fluconazole therapy.钙调神经磷酸酶促进白色念珠菌对角膜的感染，可作为靶点以增强氟康唑治疗效果。
Antimicrob Agents Chemother. 2006 Nov;50(11):3963-5. doi: 10.1128/AAC.00393-06. Epub 2006 Aug 21.
9
Combination of fluconazole with non-antifungal agents: a promising approach to cope with resistant Candida albicans infections and insight into new antifungal agent discovery.氟康唑与非抗真菌药物联合应用：一种有前途的应对耐药白色念珠菌感染的方法，并为新型抗真菌药物的发现提供了思路。
Int J Antimicrob Agents. 2014 May;43(5):395-402. doi: 10.1016/j.ijantimicag.2013.12.009. Epub 2014 Jan 22.
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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Heliyon. 2024 Mar 4;10(6):e27346. doi: 10.1016/j.heliyon.2024.e27346. eCollection 2024 Mar 30.
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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。
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The calcineruin inhibitor cyclosporine a synergistically enhances the susceptibility of Candida albicans biofilms to fluconazole by multiple mechanisms.钙调神经磷酸酶抑制剂环孢素A通过多种机制协同增强白色念珠菌生物膜对氟康唑的敏感性。
BMC Microbiol. 2016 Jun 18;16(1):113. doi: 10.1186/s12866-016-0728-1.
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High-throughput nano-biofilm microarray for antifungal drug discovery.高通量纳米生物膜微阵列用于抗真菌药物发现。
mBio. 2013 Jun 25;4(4):e00331-13. doi: 10.1128/mBio.00331-13.
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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.
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Direct effects of non-antifungal agents used in cancer chemotherapy and organ transplantation on the development and virulence of Candida and Aspergillus species.癌症化疗和器官移植中使用的非抗真菌药物对念珠菌属和曲霉属物种的发育和毒力的直接影响。
Virulence. 2011 Jul-Aug;2(4):280-95. doi: 10.4161/viru.2.4.16764. Epub 2011 Jul 1.
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Identification of antifungal compounds active against Candida albicans using an improved high-throughput Caenorhabditis elegans assay.利用改良的高通量秀丽隐杆线虫 assay 鉴定抗白色念珠菌的抗真菌化合物。
PLoS One. 2009 Sep 14;4(9):e7025. doi: 10.1371/journal.pone.0007025.
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Signaling cascades as drug targets in model and pathogenic fungi.信号级联作为模式真菌和致病真菌中的药物靶点。
Curr Opin Investig Drugs. 2008 Aug;9(8):856-64.
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Synergistic effect of calcineurin inhibitors and fluconazole against Candida albicans biofilms.钙调神经磷酸酶抑制剂与氟康唑对白色念珠菌生物膜的协同作用。
Antimicrob Agents Chemother. 2008 Mar;52(3):1127-32. doi: 10.1128/AAC.01397-07. Epub 2008 Jan 7.

本文引用的文献

1
Calcineurin is required for Candida albicans to survive calcium stress in serum.钙调神经磷酸酶是白色念珠菌在血清中抵抗钙应激所必需的。
Infect Immun. 2005 Sep;73(9):5767-74. doi: 10.1128/IAI.73.9.5767-5774.2005.
2
In vitro interactions between antifungals and immunosuppressants against Aspergillus fumigatus.抗真菌药物与免疫抑制剂对烟曲霉的体外相互作用。
Antimicrob Agents Chemother. 2004 May;48(5):1664-9. doi: 10.1128/AAC.48.5.1664-1669.2004.
3
Calcineurin is essential for virulence in Candida albicans.钙调神经磷酸酶对白色念珠菌的毒力至关重要。
Infect Immun. 2003 Sep;71(9):5344-54. doi: 10.1128/IAI.71.9.5344-5354.2003.
4
Changes in the spectrum and risk factors for invasive candidiasis in liver transplant recipients: prospective, multicenter, case-controlled study.肝移植受者侵袭性念珠菌病的谱变化及危险因素：前瞻性、多中心、病例对照研究。
Transplantation. 2003 Jun 27;75(12):2023-9. doi: 10.1097/01.TP.0000065178.93741.72.
5
Calcineurin is essential for Candida albicans survival in serum and virulence.钙调神经磷酸酶对于白色念珠菌在血清中的存活及毒力至关重要。
Eukaryot Cell. 2003 Jun;2(3):422-30. doi: 10.1128/EC.2.3.422-430.2003.
6
Calcineurin A of Candida albicans: involvement in antifungal tolerance, cell morphogenesis and virulence.白色念珠菌的钙调神经磷酸酶A：参与抗真菌耐受性、细胞形态发生和毒力。
Mol Microbiol. 2003 May;48(4):959-76. doi: 10.1046/j.1365-2958.2003.03495.x.
7
Fungal infections in the recipients of solid organ transplantation.实体器官移植受者中的真菌感染
Infect Dis Clin North Am. 2003 Mar;17(1):113-34, viii. doi: 10.1016/s0891-5520(02)00067-3.
8
Calcineurin is essential for survival during membrane stress in Candida albicans.钙调神经磷酸酶对于白色念珠菌在膜应激期间的存活至关重要。
EMBO J. 2002 Feb 15;21(4):546-59. doi: 10.1093/emboj/21.4.546.
9
Trends in invasive fungal infections in liver transplant recipients: correlation with evolution in transplantation practices.
Transplantation. 2002 Jan 15;73(1):63-7. doi: 10.1097/00007890-200201150-00011.
10
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.