Transcription factor Pho4 is involved in the regulation of drug susceptibility of Candida albicans

Abstract

Abstract:

Objective To study the influence of Candida albicans transcription factors (TFs) on drug susceptibility and the relevant regulating mechanisms, a screening of a TF deletion mutant library had been conducted.Methods The broth microdilution method and spot assay were used to determine the susceptibility of TF deletion strains.The expression of multidrug resistance genes MDR1, CDR1 and ERG11 were examined by real-time PCR, and the analysis of rhodamine 6G efflux was performed to evaluate the efflux pump activity.Results The measurement of drug minimal inhibitory concentration and spot assay indicated an increase of susceptibility to fluconazole and miconazole in PHO4 deleted mutant compared to the parental strain.Although the mutant had a higher expression of the drug resistance genes, the amount of rhodamine 6G efflux and the oxidative stress resistance of it were lower than the parental strain.Conclusion Deletion of PHO4 in C.albicans might cause a decrease in oxidative stress resistance and drug efflux ability, finally result in hypersusceptibility to antifungal drugs.

Key words: Candida albicans, transcription factor, drug susceptibility, drug efflux

CLC Number:

R379.4

QIN Yu-lin, XU Hong-tao, ZHANG Lu-lu, ZHANG Jin-yu, JIANG Yuan-ying, CAO Yong-bing. Transcription factor Pho4 is involved in the regulation of drug susceptibility of Candida albicans[J]. Chinese Journal of Mycology, 2016, 11(2): 65-69.

References

[1] Kontoyiannis DP,Lewis RE.Antifungal drug resistance of pathogenic fungi[J].Lancet,2002,359(9312):1135-1144.
[2] Morschhauser J.The genetic basis of fluconazole resistance development in Candida albicans[J].Biochim Biophys Acta,2002,1587(2-3):240-248.
[3] Morschhauser J.Regulation of multidrug resistance in pathogenic fungi[J].Fungal Genet Biol,2010:47(2):94-106.
[4] Coste AT,Karababa M,Ischer F,et al.TAC1,transcriptional activator of CDR genes,is a new transcription factor involved in the regulation of Candida albicans ABC transporters CDR1 and CDR2[J].Eukaryot Cell,2004,3(6):1639-1652.
[5] Znaidi S,Weber S,Al-Abdin OZ,et al.Genomewide location analysis of Candida albicans Upc2p,a regulator of sterol metabolism and azole drug resistance[J].Eukaryot Cell,2008,7(5):836-847.
[6] Sasse C,Schillig R,Reimund A,et al.Inducible and constitutive activation of two polymorphic promoter alleles of the Candida albicans multidrug efflux pump MDR1[J].Antimicrob Agents Chemother,2012,56(8):4490-4494.
[7] Sellam A,Tebbji F,Nantel A.Role of Ndt80p in sterol metabolism regulation and azole resistance in Candida albicans[J].Eukaryot cell,2009,8(8):1174-1183.
[8] Romanowski K,Zaborin A,Valuckaite V,et al.Candida albicans isolates from the gut of critically ill patients respond to phosphate limitation by expressing filaments and a lethal phenotype[J].PloS One,2012,7(1):e30119.
[9] Smith DA,Nicholls S,Morgan BA,et al.A conserved stress-activated protein kinase regulates a core stress response in the human pathogen Candida albicans[J].Mol Biol Cell,2004,15(9):4179-4190.
[10] Alonso-Monge R,Navarro-Garcia F,Roman E,et al.The Hog1 mitogen-activated protein kinase is essential in the oxidative stress response and chlamydospore formation in Candida albicans[J].Eukaryot Cell,2003,2(2):351-361.
[11] Herrero-de-Dios C,Alonso-Monge R,Pla J.The lack of upstream elements of the Cek1 and Hog1 mediated pathways leads to a synthetic lethal phenotype upon osmotic stress in Candida albicans[J].Fungal Genet Biol,2014,69:31-42.
[12] Monge RA,Roman E,Nombela C,et al.The MAP kinase signal transduction network in Candida albicans[J].Microbiology,2006,152(Pt 4):905-912.
[13] Urrialde V,Prieto D,Pla J,et al.The Pho4 transcription factor mediates the response to arsenate and arsenite in Candida albicans[J].Front Microbiol,2015,6:118.

[1]	ZHANG Jing-yun, PENG Jing-wen, WANG Qiong, GAO Ying, CHEN Wan-xin, SHEN Yong-nian, LI Dong-mei, SHE Xiao-dong, LIU Wei-da. The role of EGFR in the pathogenesis of vaginal candidiasis [J]. Chinese Journal of Mycology, 2020, 15(2): 65-71.
[2]	TAN Jing-wen, XU Hong, SONG Jin-feng, GAO Zhi-qin, YANG Hong, YANG Lian-juan, WEN Hai. In vitro antifungal susceptibility of polyhexamethylene biguanide against common superficial fungal species [J]. Chinese Journal of Mycology, 2020, 15(2): 93-96.
[3]	LIU Yu-lei, LIU Mei-qing, WANG Li, YUAN Hui, GUO Li-na. Epidemiology, antifungal drugs susceptibilities and prognosis of catheter-related candidemia in cardiovascular disease patients [J]. Chinese Journal of Mycology, 2020, 15(1): 37-42.
[4]	WANG Yu-ting, WANG Yu-zhu, LIU Jin-yan, MENG Ling-ning, LI Wei-hua, XIANG Ming-jie. Comparison of immune responses of yeast form and hyphae form Candida albicans to infection of vaginal epithelial cells [J]. Chinese Journal of Mycology, 2019, 14(4): 193-199.
[5]	CAI Qing, YANG Lian-juan, GAO Zhi-qin, REN Hong-jin, YANG Hong, TAN Jing-wen. In vitro study of the effect of romidepsin on fluconazole againgst Candida albicans [J]. Chinese Journal of Mycology, 2019, 14(4): 200-203,216.
[6]	SHI Gao-xiang, JIANG Jing-jing, WANG Yun-xia, ZHAO Ting, SHAO Jing, WANG Tian-ming, Wang Chang-zhong. Inhibitory effect of extract of Sophorae Flavescentis Radix-Cnidii Fructus Couplet medicines against Candida albicans isolate from VVC [J]. Chinese Journal of Mycology, 2019, 14(3): 147-153.
[7]	GAO Ying, WANG Qiong, LIANG Guan-zhao, SHE Xiao-dong, SHI Dong-mei, SHEN Yong-nian, SU Xiao-hong, LI Dong-mei, LIU Wei-da. The role of ALS3 and SSA1 gene expression of Candida albicans in the immune mechanism of vaginal candidiasis [J]. Chinese Journal of Mycology, 2019, 14(2): 65-69.
[8]	LIU Yu, YAN Lan, JIANG Yuan-ying. Study on the mechanism of NT-89 against Candida albicans based on quantitative proteomics [J]. Chinese Journal of Mycology, 2019, 14(2): 70-77.
[9]	MENG Ling-ning, LIU Jin-yan, ZHAO Yue, WANG Yu-ting, XIANG Ming-jie. Preparation of recombinant proteinphosphopantetheinyl transferase Ppt2 of Candida albicans [J]. Chinese Journal of Mycology, 2019, 14(1): 11-15.
[10]	SUI Xue, JIANG Yuan-ying, YAN Lan. Prediction of the epitopes of the cell wall protein Csp37 in Candida albicans [J]. Chinese Journal of Mycology, 2018, 13(6): 327-334.
[11]	WANG Yu-ting, LIU Jin-yan, ZHAO Yue, MENG Ling-ning, XIANG Ming-jie. Research progress of White-Gray-Opaque phenotypic switching system in Candida albicans [J]. Chinese Journal of Mycology, 2018, 13(6): 367-370.
[12]	HU Tang-ling, SHI Gao-xiang, XU Zhi-qing, DUAN Qiang-jun, SHAO Jing, WANG Tian-ming, WU Da-qiang, WANG Chang-zhong. Inhibitory effect of Butyl alcohol extract of BaiTouWeng decoction on Candida albicans cell wall [J]. Chinese Journal of Mycology, 2018, 13(5): 262-267.
[13]	ZHAO Xiao-xia, FENG Wen-Li. Research progress of adhesion-related genes of Candida albicans [J]. Chinese Journal of Mycology, 2018, 13(5): 309-313.
[14]	XU Hui-hui, JIANG Ling-huo. Inactivation of Candida albicans CaMIT1 gene with CRISPR/Cas9 approach and the phenotype analysis of its homozygous mutant [J]. Chinese Journal of Mycology, 2018, 13(4): 201-207.
[15]	ZHANG Xiao-long, LU Ren-yi, YAN Lan, JIANG Yuan-ying. Disruption and functional characterization of SIM1 gene in Candida albicans [J]. Chinese Journal of Mycology, 2018, 13(4): 223-228.