基于Hog-MAPK信号通路探讨白念珠菌氟康唑耐药机制的实验研究

中国真菌学杂志　 2015, Vol. 10 　Issue (6): 345-351.

基于Hog-MAPK信号通路探讨白念珠菌氟康唑耐药机制的实验研究

闻轶旸, 黄欣, 沈帅帅, 赵敬军

上海市同济医院皮肤科, 上海 200065

收稿日期:2015-11-18 出版日期:2015-12-28 发布日期:2015-12-28
通讯作者: 黄欣,E-mail:alida_huang@163.com E-mail:alida_huang@163.com
作者简介:闻轶旸,男(汉族),硕士,住院医师.E-mail:414907668@qq.com
基金资助:
上海市科委自然科学基金(13ZR1437900)

A Study of fluconazole resistance mechanism of Candida albicans based on Hog-MAPK signal pathway

WEN Yi-yang, HUANG Xin, SHEN Shuai-shuai, ZHAO Jing-jun

Department of Dermatology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065

Received:2015-11-18 Online:2015-12-28 Published:2015-12-28

摘要/Abstract

摘要：

目的探讨Hog-MAPK信号通路在白念珠菌氟康唑耐药机制中的作用。方法通过Real-Time PCR、Western blot等方法比较白念珠菌氟康唑敏感株与耐药株Hog-MAPK信号通路相关的HOG1等基因的mRNA表达,以及磷酸化p38 MAPK蛋白表达的差异,并应用微量液基稀释法检测白念珠菌HOG1基因缺陷株及其原始亲代菌株/标准株对氟康唑MIC值的差异。结果白念珠菌氟康唑敏感株与耐药株之间Hog-MAPK信号通路相关基因mRNA表达和蛋白表达存在一定差异性,敏感株的表达在一定程度上低于耐药株,HOG1基因缺陷株对氟康唑更为敏感。结论白念珠菌氟康唑耐药性可能与Hog-MAPK信号通路中部分基因和蛋白表达有关,这些基因和蛋白表达的降低可能使耐药性发生改变。

关键词: 白念珠菌, Hog-MAPK信号通路, 耐药性

Abstract:

Obejectives To investigate the role of Hog-MAPK signaling pathway in the fluconazole resistance mechanism of Candida albicans mechanism.Methods Using Real-Time PCR and Western blot to compare the expression of HOG1 gene and Phosphorylation p38 MAPK protein from Hog-MAPK signaling pathway in fluconazole sensitive strain and resistance strain,then dectect the fluconazole MIC of Candida albicans HOG1 mutant and its original parent strain/standard strain.Results The difference of the expression of Hog-MAPK signaling pathway related gene and protein is found between Candida albicans fluconazole sensitive strain and resistant strain,the expression of sensitive strain is less than resistant strain to a certain extent,and HOG1 mutant strain is more sensitive to fluconazole.Conclusion The fluconazole resistance mechanism of Candida albicans may be associated with some gene and protein from Hog-MAPK pathway.The decreased expression of these genes and proteins may cause change of resistance to fluconazole.

Key words: Candida albicans, Hog-MAPK signaling pathway, drug resistance

中图分类号:

R379.4

闻轶旸, 黄欣, 沈帅帅, 赵敬军. 基于Hog-MAPK信号通路探讨白念珠菌氟康唑耐药机制的实验研究[J]. 中国真菌学杂志, 2015, 10(6): 345-351.

WEN Yi-yang, HUANG Xin, SHEN Shuai-shuai, ZHAO Jing-jun. A Study of fluconazole resistance mechanism of Candida albicans based on Hog-MAPK signal pathway[J]. Chinese Journal of Mycology, 2015, 10(6): 345-351.

参考文献

[1] Schelenz S,Abdallah S,Gray G et al.Epidemiology of oral yeast colonization and infection in patients with hematological malignancies,head neck and solid tumors[J].J Oral Pathol Med,2011,40(1):83-89.
[2] Walsh TJ,Groll A,Hiemenz J,Fleming R,Roilides E,Anaissie E.Infections due to emerging and uncommon medically important fungal pathogens[J].Clin Microbiol Infect,2004,10(Suppl 1):48-66.
[3] Alvez F,Figueras C,Rosello E.Emerging invasive fungal infections[J].An Pediatr(Barc),2010,73(1):52.E1-6.
[4] 廖万清.深部真菌感染治疗进展[J].中国麻风皮肤病杂志,2003,19(6):597-600.
[5] 廖璞,程海平.白色念珠菌致病性研究[J].中华医院感染学杂志,2005,15(4):470.
[6] Bader T,Schroppel K,Bentink S,Agabian N,Kohler G,Morshhauser J.Role of calcineurin in stress resistance,morphogensis,and virulence of a Candida albicans wild-type strain[J].Infect Immun,2006,74(7):4366-4369.
[7] White TC,Pfaller MA,Rinaldi MG et al.Stable azole drug resistance associated with a substrain of Candida albicans from an HIV-infected patient[J].Oral Dis,1997,3(Suppl1):S102-109.
[8] 黄悦,张子平,程波.HOG1基因对白念珠菌超微结构的影响[J].中国真菌学杂志,2010,5(1):13-16.
[9] Referencemethod for broth dilution antifungal susceptibility testing of yeasts;approved standard-third edition.(M27-A3)[J].Infobase,2009,28(14).
[10] Cuenda A,Rousseau S.p38 MAP-kinases pathway regulation,function and role in human diseases[J].Biochim Biophys Acta,2007,1773(8):1358-1375.
[11] Cheetham J,Maccallum DM,Doris KS,et al.MAPKKK-independent regulation of the HOG1 stress-activated protein kinase in Candida albicans[J].J Biol Chem,2011,286(49):42002-42016.
[12] Vivaneos AP,Jara M,Zuin A,et al.Oxidative stress in Schizosaccharomyces pombe:different H₂O₂ levels,different response pathways[J].Mol Genet Genomics,2006,276(6):495-502.
[13] 黄金竹,母连军.抗真菌约物的研究进展[J].World Notes on Antibiotics,2007,28(6):246-251.
[14] 颜钰,曹颖瑛,姜远英.白念珠菌耐药机制新进展[J].中国真菌学杂志,2013,8(5):311-315.
[15] 王端礼.医学真菌学-实验室检验指南[M].第一版.北京:人民卫生出版社,2005:103-107.