BDSF抑制白念珠菌生物膜的形成
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
白念珠菌是一种极其重要的条件致病真菌,白念珠菌可形成生物膜,极大的增强了其抗药性,是临床上的一大难题。本实验中通过显微镜观察的方法,检测了cis-BDSF和trans-BDSF在体外对于白念珠菌的生长、出芽以及生物膜形成的影响。通过静置微孔板法构建白念珠菌生物膜模型,利用XTT法定量测定在白念珠菌生物膜生长的不同时间加入不同浓度的cis-BDSF和trans-BDSF对白念珠菌生物膜形成的抑制作用,并且通过显微镜观察其对生物膜结构和形成的影响,northern杂交检测cis-BDSF和trans-BDSF处理过的生物膜中菌丝特异性基因HWP1的表达变化。结果显示300μM的cis-BDSF和trans-BDSF均可抑制白念珠菌酵母相的生长,出芽抑制率可达70%。在0小时和1小时时加入300μM的cis-BDSF和trans-BDSF,对于生物膜的抑制率均可达90%(0小时)和60%(1小时),显著高于法尼醇和DSF。然而,四种药均不能对已经形成的生物膜造成影响。Northern杂交结果表明cis-BDSF和trans-BDSF可下调HWP1的表达。实时荧光定量分析同样显示经60μM的cis-BDSF和trans-BDSF处理,白念珠菌生物膜模型中HWP1和ALS3的表达量分别下调约90%(cis-BDSF)和70-80%(trans-BDSF),证明在生物膜形成早期(0或1小时)加入cis-BDSF和trans-BDSF可以显著抑制白念珠菌生物膜的形成,低浓度(3μM、30μM和60μM)时主要通过抑制其形态转变及菌丝相的附着实现的,而高浓度(300μM)时则通过抑制形态转变和菌丝相附着以及酵母相的生长的联合作用实现的。Cis-BDSF和trans-BDSF作为可能的治疗方法值得进行进一步研究。
Candida is an important opportunistic human fungal pathogen. Infections caused by C. albicans are related to the formation of a biofilm, which enhances the resistance of the C. albicans defense system, increases its resistance to antifungal drugs, and induces increase drug tolerance. Therefore, it makes clinical care more challenging. The in vitro activities of cis-BDSF (cis-2-dodecenoic acid) and trans-BDSF (trans-2-dodecenoic acid) against Candida albicans growth, germ tube germination and biofilm formation were estimated by optical density and microscopic assessment. C. albicans biofilms were prepared using the static microtitre plate model. The quantitative analysis of formation of biofilm was performed by XTT [2,3-bis (2-methoxy-4-nitro-5-sulfo-phenyl)-2H-tetrazolium-5-carboxanilide] reduction assay to evaluate the effect of different concentrations of cis-BDSF and trans-BDSF at different times. The reduction in biofilm structure and formation was visualized by inverted microscopy. Northern blot was employed to estimate the mRNA expression levels of the hyphae specific gene HWP1. We found that at 300μM, cis-BDSF and trans-BDSF inhibited yeast growth and reduced germ tube formation by 70%. At 300μM, by exogenous addition at 0 and 1 h, cis-BDSF and trans-BDSF reduced biofilm formation by about 90%(0 h) and 60%(1 h) and were more effective against biofilm formation than farnesol and DSF (cis-11-methyl-2-dodecenoic acid). However, none of the four drugs were able to destroy pre-formed biofilms. Northern blot showed that the mRNA expression levels of HWP1, were down regulated after cis-BDSF or trans-BDSF treatment. ALSo real-time RT-PCR analysis showed that both HWP1 and ALS3 were down regulated bycis-BDSF (90%)andtrans-BDSF (70-80%) at 60μM, demonstrating that cis-BDSF and trans-BDSF can strongly block biofilm formation in C. albicansby interfering with the morphological switch and the adhesion of hypha, and ALSo conbined with the inhibition of the yeast growth at higher concentration (300μM). The results suggest that they may be potential therapeutic agent worthy of further study.
引文
[1]Cao, YY; Cao, YB; Xu, Z; Ying, K; Li, Y; Xie, Y; Zhu, ZY; Chen, WS; Jiang, YY. cDNA microarray analysis of differential gene expression in Candida albicans biofilm exposed to farnesol [J]. Antimicrobial Agents and Chemotherapy,2005,49(2):584-589.
    [2]Pierce, CG; Thomas, DP; Lopez-Ribot, JL.Effect of tunicamycin on Candida albicans biofilm formation and maintenance [J]. Journal of Antimicrobial Chemotherapy,2009,63(3):473-479.
    [3]Douglas, U. Candida biofilms and their role in infection [J]. Trends in Microbiology,2003,11(1): 30-36.
    [4]Kumamoto, CA. Candida biofilms [J]. Current Opinion in Microbiology,2002,5(6):608-611.
    [5]Borecka-Melkusova, S; Moran, GP; Sullivan, DJ; Kucharikova, S; Chorvat, D; Bujdakova, H. The expression of genes involved in the ergosterol biosynthesis pathway in Candida albicans and Candida dubliniensis biofilms exposed to fluconazole [J]. Mycoses,2009,52(2):118-128.
    [5]Lo, HJ; Kohler, JR; DiDomenico, B; Loebenberg, D; Cacciapuoti, A; Fink, GR. Nonfilamentous C-albicans mutants are avirulent [J]. Cell,1997,90(5):939-949.
    [7]Brown, AJP; Gow, NAR. Regulatory networks controlling Candida albicans morphogenesis [J]. Trends in Microbiology,1999,7(8):333-338.
    [8]Brown, DH; Giusani, AD; Chen, X; Kumamoto, CA. Filamentous growth of Candida albicans in response to physical environmental cues and its regulation by the unique CZF1 gene [J]. Molecular Microbiology,1999,34(4):651-662.
    [9]Bassler, BL; Wright, M; Showalter, RE; Silverman, MR. INTERCELLULAR SIGNALING IN VIBRIO-HARVEYI-SEQUENCE AND FUNCTION OF GENES REGULATING EXPRESSION OF LUMINESCENCE [J]. Molecular Microbiology,1993,9(4):773-786.
    [10]Fuqua, WC; Winans, SC; Greenberg, EP. QUORUM SENSING IN BACTERIA-THE LUXR-LUXI FAMILY OF CELL DENSITY-RESPONSIVE TRANSCRIPTIONAL REGULATORS [J]. Journal of Bacteriology,1994, 176(2):269-275.
    [11]Withers, H; Swift, S; Williams, P. Quorum sensing as an integral component of gene regulatory networks in Gram-negative bacteria [J]. Current Opinion in Microbiology,2001,4(2):186-193.
    [12]Senadheera, D; Cvitkovitch, DG In Bacterial Signal Transduction:Networks and Drug Targets,2008; Vol.631; pp 178-188.
    [13]Ruby, EG. Lessons from a cooperative, bacterial-animal association:The Vibrio fischeri Euprymna scolopes light organ symbiosis [J]. Annual Review of Microbiology,1996,50(591-624.
    [14]罗利龙;罗瑞娟;邱健;宋水山.细菌群体感应及其感染策略的研究进展[J].生物学杂志,2010,27(6):4.
    [15]Interdomain cross talk; Cugini, C; Kolter, DA; A., HD, Eds.; ASM Press:Washington DC,2008.
    [16]Metabolites as intercellular signALS for regulation of community level traits.; Monds, RD; O'Toole, GA, Eds.; ASM Press:Washington DC,2008.
    [17]Lingappa, BT; Prasad, M; Lingappa, Y; Hunt, DF; Biemann, K. PHENETHYL ALCOHOL AND TRYPTOPHOL-AUTOANTIBIOTICS PRODUCED BY FUNGUS CANDIDA ALBICANS [J]. Science,1969. 163(3863):192-&.
    [18]Dabrowa, N; Taxer, SSS; Howard, DH. GERMINATION OF CANDIDA-ALBICANS INDUCED BY PROLINE [J]. Infection and Immunity,1976,13(3):830-835.
    [19]Hazen, KC; Cutler, JE. AUTO-REGULATION OF GERM TUBE FORMATION BY CANDIDA-ALBICANS [J]. Infection and Immunity,1979,24(3):661-666.
    [20]Hazen, KC; Cutler, JE. ISOLATION AND PURIFICATION OF MORPHOGENIC AUTOREGULATORY SUBSTANCE PRODUCED BY CANDIDA-ALBICANS [J]. Journal of Biochemistry,1983,94(3):777-783.
    [21]Hornby, JM; Jensen, EC; Lisec, AD; Tasto, JJ; Jahnke, B; Shoemaker, R; Dussault, P; Nickerson, KW. Quorum sensing in the dimorphic fungus Candida albicans is mediated by farnesol [J]. Applied and Environmental Microbiology,2001,67(7):2982-2992.
    [22]Oh, KB; Miyazawa, H; Naito, T; Matsuoka, H. Purification and characterization of an autoregulatory substance capable of regulating the morphological transition in Candida albicans [J]. Proceedings of the National Academy of Sciences of the United States of America,2001,98(8):4664-4668.
    [23]Shchepin, R; Dumitru, R; Nickerson, KW; Lund, M; Dussault, PH. Biologically active fluorescent farnesol analogs [J]. Chemistry & Biology,2005,12(6):639-641.
    [24]Molero, G; DiezOrejas, R; NavarroGarcia, F; Monteoliva, L; Pla, J; Gil, C; SanchezPerez, M; Nombela, C. Candida albicans:genetics, dimorphism and pathogenicity. [J]. Int and Microbiol,1998,1(12.
    [25]Ramage. G; Saville, SP; Wickes, BL; Lopez-Ribot, JL. Inhibition of Candida albicans biofilm formation by farnesol, a quorum-sensing molecule [J]. Applied and Environmental Microbiology,2002, 68(11):5459-5463.
    [26]Wang, LH; He, YW; Gao, YF; Wu, JE; Dong, YH; He, CZ; Wang, SX; Weng, LX; Xu, JL; Tay, L; Fang, RX; Zhang, LH. A bacterial cell-cell communication signal with cross-kingdom structural analogues [J]. Molecular Microbiology,2004,51(3):903-912.
    [27]Chen, H; Fujita, M; Feng, QH; Clardy, J; Fink, GR. Tyrosol is a quorum-sensing molecule in Candida albicans [J]. Proceedings of the National Academy of Sciences of the United States of America,2004, 101(14):5048-5052.
    [28]Nickerson, KW; Atkin, AL; Hornby, JM. Quorum sensing in dimorphic fungi:Farnesol and beyond [J]. Applied and Environmental Microbiology,2006,72(6):3805-3813.
    [29]Daniels, R; Vanderleyden, J; Michiels, J. Quorum sensing and swarming migration in bacteria [J]. Fems Microbiology Reviews,2004,28(3):261-289.
    [30]Kaiser, D. Signaling in myxobacteria [J]. Annual Review of Microbiology,2004,58(75-98.
    [31]Parsek, MR; Greenberg, EP. Sociomicrobiology:the connections between quorum sensing and biofilms [J]. Trends in Microbiology,2005,13(1):27-33.
    [32]Suntharalingam, P; Cvitkovitch, DG. Quorum sensing in streptococcal biofilm formation [J]. Trends in Microbiology,2005,13(1):3-6.
    [33]Visick, KL; Fuqua, C. Decoding microbial chatter:Cell-cell communication in bacteria [J]. Journal of Bacteriology,2005,187(16):5507-5519.
    [34]Zhang, LH; Dong, YH. Quorum sensing and signal interference:diverse implications [J]. Molecular Microbiology,2004,53(6):1563-1571.
    [35]Dong, YH; Zhang, XF; Xu, JL; Zhang, LH. Insecticidal Bacillus thuringiensis silences Erwinia carotovora virulence by a new form of microbial antagonism, signal interference [J]. Applied and Environmental Microbiology,2004,70(2):954-960.
    [36]Hogan, DA; Vik, A; Kolter, R. A Pseudomonas aeruginosa quorum-sensing molecule influences Candida albicans morphology [J]. Molecular Microbiology,2004,54(5):1212-1223.
    [37]Boon, C; Deng, YY; Wang, LH; He, YW; Xu, JL; Fan, Y; Pan, SQ:Zhang, LH. A novel DSF-like signal from Burkholderia cenocepacia interferes with Candida albicans morphological transition [J].!sme Journal,2008,2(1):27-36.
    [38]Sharkey, LL; McNemar, MD; Saporito-lrwin, SM; Sypherd, PS; Fonzi, WA. HWP1 functions in the morphological development of Candida albicans downstream of EFG1, TUP1, and RBF1 [J]. Journal of Bacteriology,1999,181(17):5273-5279.
    [39]Chen, JY; Zhou, S; Wang, Q; Chen, X; Pan, T; Liu, HP. Crk1, a novel Cdc2-related protein kinase, is required for hyphal development and virulence in Candida albicans [J]. Molecular and Cellular Biology, 2000,20(23):8696-8708.
    [40]Csank, C; Schroppel, K; Leberer, E; Harcus, D; Mohamed, O; Meloche, S; Thomas, DY; Whiteway, M. Roles of the Candida albicans mitogen-activated protein kinase homolog, Ceklp, in hyphal development and systemic candidiasis [J]. Infection and Immunity,1998,66(6):2713-2721.
    [41]Chen, JY; Chen, J; Lane, S; Liu, HP. A conserved mitogen-activated protein kinase pathway is required for mating in Candida albicans [J]. Molecular Microbiology,2002,46(5):1335-1344.
    [42]Eisman, B; Alonso-Monge, R; Roman, E; Arana, D; Nombela, C; Pla, J. The Cek1 and Hog1 mitogen-activated protein kinases play complementary roles in eell wall biogenesis and chlamydospore formation in the fungal pathogen Candida albicans [J]. Eukaryotic Cell,2006,5(2): 347-358.
    [43]DiezOrejas, R; Molero, G; NavarroGarcia, F; Pla, J; Nombela, C; SanchezPerez, M. Reduced virulence of Candida albicans MKC1 mutants:A role for mitcgen-activated protein kinase in pathogenesis [J]. Infection and Immunity,1997,65(2):833-837.
    [44]Willoughby, D; Cooper, DMF. Organization and Ca2+ regulation of adenylyl cyclases in cAMP microdomains [J]. Physiological Reviews,2007,87(3):965-1010.
    [45]Rocha, CRC; Schroppel, K; Harcus, D; Marcil, A; Dignard D; Taylor, BN; Thomas, DY; Whiteway, M; Leberer, E. Signaling through adenylyl cyclase is essential for hyphal growth and virulence in the pathogenic fungus Candida albicans [J]. Molecular Biology of the Cell,2001,12(11):3631-3643.
    [46]Cao, F; Lane, S; Raniga, PP; Lu, Y; Zhou, Z; Ramon, K; Chen, JY; Liu, HP. The Flo8 transcription factor is essential for hyphal development and virulence in Candida albicans [J]. Molecular Biology of the Cell, 2006,17(1):295-307.
    [47]Klengel, T; Liang, WJ; Chaloupka, J; Ruoff, C; Schroppel, K; Naglik, JR; Eckert, SE; Mogensen, EG; Haynes, K; Tuite, MF; Levin, LR; Buck, J; Muhlschlegel, FA. Fungal adenylvl cyclase integrates CO2 sensing with cAMP signaling and virulence [J]. Current Biology,2005,15(22):2021-2026.
    [48]Aguilera, j; Van Dijken, JP; De Winde, JH; Pronk, JT. Carbonic anhydrase (Nce103p):an essential biosynthetic enzyme for growth of Saccharomyces cerevisiae at atmospheric carbon dioxide pressure [J]. Biochemical Journal,2005,391(311-316.
    [49]Bahn, YS; Cox, GM; Perfect, JR; Heitman, J. Carbonic anhydrase and CO2 sensing during Cryptocloccus neoformans growth, differentiation, and virulence [J]. Current Biology,2005,15(22): 2013-2020.
    [50]Gotz, R; Gnann, A; Zimmermann, FK. Deletion of the carbonic anhydrase-like gene NCE103 of the yeast Saccharomyces cerevisiae causes an oxygen-sensitive growth defect [J]. Yeast,1999,15(10A): 855-864.
    [51]Miller, MB; Bassler, BL. Quorum sensing in bacteria [J]. Annual Review of Microbiology,2001, 55(165-199.
    [52]Clark, D; Rowlett, RS; Coleman, JR; Klessig, DF. Complementation of the yeast deletion mutant Delta NCE103 by members of the beta class of carbonic anhydrases is dependent on carbonic anhydrase activity rather than on antioxidant activity [J]. Biochemical Journal,2004,379(609-615.
    [53]Buffo, J; Herman, MA; Soil, DR. A CHARACTERIZATION OF PH-REGULATED DIMORPHISM IN CANDIDA-ALBICANS [J]. Mycopathologia,1984,85(1-2):21-30.
    [54]Pratt, LA; Kolter, R. Genetic analyses of bacterial biofilm formation [J]. Current Opinion in Microbiology,1999,2(6):598-603.
    [55]Costerton, JW; Stewart, PS; Greenberg, EP. Bacterial biofilms:A common cause of persistent infections [J]. Science,1999,284(5418):1318-1322.
    [56]王丹敏;靳颖;董小青;刘丽英.白色念珠菌生物膜生长动力学分析和形态学观察[J].武警医学院学报,2010,19(9):4.
    [57]Oral Candidiasis; Samaranayake, LP; MacFarlane, TW, Eds.; Wright-Butterworth:London,1990.
    [58]Donlan, RM; Costerton, JW. Biofilms:Survival mechanisms of clinically relevant microorganisms [J]. Clinical Microbiology Reviews,2002,15(2):167-+.
    [59]Baillie, GS; Douglas, U. Role of dimorphism in the development of Candida albicans biofilms [J]. Journal of Medical Microbiology,1999,48(7):671-679.
    [60]Chandra, J; Kuhn, DM; Mukherjee, PK; Hoyer, LL; McCormick, T; Ghannoum, MA. Biofilm formation by the fungal pathogen Candida albicans:Development, architecture, and drug resistance [J]. Journal of Bacteriology,2001,183(18):5385-5394.
    [61]Ramage, G; Vande Walle, K; Wickes, BL; Lopez-Ribot, JL. Biofilm formation by Candida dubliniensis [J]. Journal of Clinical Microbiology,2001,39(9):3234-3240.
    [62]Ramage, G; VandeWalle, K; Lopez-Ribot, JL; Wickes, BL. The filamentation pathway controlled by the Efgl regulator protein is required for normal biofilm formation and development in Candida albicans [J]. Ferms Microbiology Letters,2002,214(1):95-100.
    [63]Ramage, G; Bachmann, S; Patterson, TF; Wickes, BL; Lopez-Ribot, JL. Investigation of multidrug efflux pumps in relation to fluconazole resistance in Candida albicans biofilms [J]. Journal of Antimicrobial Chemotherapy,2002,49(6):973-980.
    [64]Hawser, SP; Douglas, U. BIOFILM FORMATION BY CANDIDA SPECIES ON THE SURFACE OF CATHETER MATERIALS IN-VITRO [J]. Infection and Immunity,1994,62(3):915-921.
    [65]Mukherjee, PK; Mohamed, S; Chandra, J; Kuhn, D; Liu, SQ; Antar, OS; Munyon, R; Mitchell, AP; Andes, D; Chance, MR; Rouabhia, M; Ghannoum, MA. Alcohol dehydrogenase restricts the ability of the pathogen Candida albicans to form a biofilm on catheter surfaces through an ethanol-based mechanism [J]. Infection and Immunity,2006,74(7):3804-3816.
    [66]Radford, DR; Sweet, SP; Challacombe, SJ; Walter, JD. Adherence of Candida albicans to denture-base materiALS with different surface finishes [J]. Journal of Dentistry,1998,26(7):577-583.
    [67]Chandra, J; Patel, JD; Li, J; Zhou, GY; Mukherjee, PK; McCormick, TS; Anderson, JM; Ghannoum, MA. Modification of surface properties of biomateriALS influences the ability of Candida albicans to form biofilms [J]. Applied and Environmental Microbiology,2005,71(12):8795-8801.
    [68]Parahitiyawa, NB; Samaranayake, YH; Samaranayake, LP; Ye, J; Tsang, PWK; Cheung, BPK; Yau, JYY; Yeung, SKW. Interspecies variation in Candida biofilm formation studied using the Calgary biofilm device [J]. Apmis,2006,114(4):298-306.
    [69]Nikawa, H; Hamada, T; Yamamoto, T; Kumagai, H. Effects of salivary or serum pellicles on the Candida albicans growth and biofilm formation on soft lining materiALS in vitro [J]. Journal of Oral Rehabilitation,1997,24(8):594-604.
    [70]Thein, ZM; Samaranayake, YH; Samaranayake, LP. In vitro biofilm formation of Candida albicans and non-albicans Candida species under dynamic and anaerobic conditions [J]. Archives of Oral Biology, 2007,52(8):761-767.
    [71]Biswas, SK; Chaffin, WL. Anaerobic growth of Candida albicans does not support biofilm formation under similar conditions used for aerobic biofilm [J]. Current Microbiology,2005,51(2):100-104.
    [72]Revnaud, AH; Nygaard-Ostby, B; Boygard, GK; Eribe, ER; Olsen, I; Gjermo, R. Yeasts in periodontal pockets [J]. Journal of Clinical Periodontology,2001,28(9):860-864.
    [73]Siqueira, JF; Sen, BH. Fungi in endodontic infections [J]. Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontics,2004,97(5):632-641.
    [74]Baillie, GS; Douglas, U. Effect of growth rate on resistance of Candida albicans biofilms to antifungal agents [J]. Antimicrobial Agents and Chemotherapy,1998,42(8):1900-1905.
    [75]AI-Fattani, MA; Douglas, U. Biofilm matrix of Candida albicans and Candida tropicalis:chemical composition and role in drug resistance [J]. Journal of Medical Microbiology,2006,55(8):999-1008.
    [76]Hawser, SP; Baillie, GS; Douglas, U. Production of extracellular matrix by Candida albicans biofilms [J]. Journal of Medical Microbiology,1998,47(3):253-256.
    [77]Jin, Y; Yip, HK; Samaranayake, YH; Yau, JY; Samaranayake, LP. Biofilm-forming a ability of Candida albicans is unlikely to contribute to high levels of oral yeast carriage in cases of human immunodeficiency virus infection [J]. Journal of Clinical Microbiology,2003,41(7):2961-2967.
    [78]Nobile, GJ; Mitchell, AP. Regulation of cell-surface genes and biofilm formation by the C-albicans transcription factor Bcrlp [J]. Current Biology,2005,15(12):1150-1155.
    [79]Nobile, CJ; Andes, DR; Nett, JE; Smith, FJ; Yue, F; Phan, QT; Edwards, JE; Filler, SG; Mitchell, AP. Critical role cf Bcr1-dependent adhesins in C-albicans biofilm formation in vitro and in vivo [J]. Plos Pathogens,2006,2(7):636-649.
    [80]Nobile, CJ; Nett, JE; Andes, DR; Mitchell, AP. Function of Candida albicans adhesin HWP1 in biofilm formation [J]. Eukaryotic Cell,2006,5(10):1604-1610.
    [81]Green, CB; Cheng, G; Chandra, J; Mukherjee, P; Ghannoum, MA; Hoyer, LL.RT-PCR detection of Candida albicans ALS gene expression in the reconstituted human epithelium (RHE) model of oral candidiasis and in model biofilms [J]. Microbiology-Sgm,2004,150(267-275.
    [82]Hoyer, LL; Green, CB; Oh, SH; Zhao, XM. Discovering the secrets of the Candida albicans agglutinin-like sequence (ALS) gene family-a sticky pursuit [J]. Medical Mycology,2008,46(1):1-15.
    [83]Argimon, S; Wishart, JA; Leng, R; Macaskill, S; Mavor, A; Aiexandris, T; Nicholls, S; Knight, AW; Enjalbert, B; Walmsley, R; Odds, FC; Gow, NAR; Brown, AJP. Developmental regulation of an adhesin gene during cellular morphogenesis in the fungal pathogen Candida albicans [J). Eukaryotic Cell,2007, 6(4):682-692.
    [84]Ramage, G; vande Walle, K; Wickes, BL; Lopez-Ribot, JL. Standardized method for in vitro antifungal susceptibility testing of Candida albicans biofilms [J]. Antimicrobial Agents and Chemotherapy,2001,45(9):2475-2479.
    [85]沈亮亮;叶元康.氟康唑与5-氟胞嘧啶体外联合抗白念珠菌临床分离株的研究[J].同济大学学报(医学版),2005,26(6):3.
    [86]刘小平;樊尚荣;李建武.妇科门诊患者外阴阴道念珠菌病的检出率和抗真菌药物敏感性研究[J].中国妇产科临床杂志,2004,5(2):5.
    [87]Dupont, PF. CANDIDA-ALBICANS, THE OPPORTUNIST-A CELLULAR AND MOLECULAR PERSPECTIVE [J]. Journal of the American Podiatric Medical Association,1995,85(2):104-115.
    [88]Braun, P. Surface hydrophobicity enchance corticosterone incorporation in Candida albicans. [J]. Infection and Immunity,1994,62(3.
    [89]Louie, A; Dixon, DM; Elmaghrabi, EA; Burnett, JW; Baltch, AL; Smith, RP. RELATIONSHIP BETWEEN CANDIDA-ALBICANS EPIDERMOLYTIC PROTEINASE ACTIVITY AND VIRULENCE IN MICE [J]. Journal of Medical and Veterinary Mycology,1994,32(1):59-64.
    [90]Cannon, RD; Holmes, AR; Mason, AB; Monk, BC. ORAL CANDIDA-CLEARANCE, COLONIZATION, OR CANDIDIASIS [J]. Journal of Dental Research,1995,74(5):1152-1161.
    [91]Gaur, NK; Klotz, SA; Henderson, RL. Overexpression of the Candida albicans ALA1 gene in Saccharomyces cerevisiae results in aggregation following attachment of yeast cells to extracellular matrix proteins, adherence properties similar to those of Candida albicans [J]. Infection and Immunity, 1999,67(11):6040-6047.
    [92]Sundstrom, P. Adhesins in Candida albicans [J]. Current Opinion in Microbiology,1999,2(4): 353-357.
    [93]温旺荣;王德春;陈红;朱忠勇.白念珠菌的毒力研究——蛋白酶活力的测定[J].中国人兽共患病杂志,1999,15(6):4.
    [94]Ray, TL; Payne, CD. SCANNING ELECTRON-MICROSCOPY OF EPIDERMAL ADHERENCE AND CAVITATION IN MURINE CANDIDIASIS-A ROLE FOR CANDIDA ACID PROTEINASE [J]. Infection and Immunity,1988,56(8):1942-1949.
    [95]Kyung, JKC; Lehman, D; Good, C; Magee, PT. GENETIC-EVIDENCE FOR ROLE OF EXTRACELLULAR PROTEINASE IN VIRULENCE OF CANDIDA-ALBICANS [J]. Infection and Immunity,1985,49(3):571-575.
    [96]王丹敏;韩景天;董小青;屈野.白色念珠菌蛋白酶与其毒力关系的研究[J].中国微生态杂志,2000,12(4):3.
    [97]苑天红;王明永;吴升伟;王正蓉;吴承龙.白念珠菌二相性与致病性关系[J].中国公共卫生,2005,21(1):2.
    [98]石宏宴;马荣;王彦.149株念珠菌鉴定与药敏分析[J].大连医科大学学报,2007,29(4):2.
    [99]Hawser, SP; Douglas, U. RESISTANCE OF CANDIDA-ALBICANS BIOFILMS TO ANTIFUNGAL AGENTS IN-VITRO [J]. Antimicrobial Agents and Chemotherapy,1995,39(9):2128-2131.
    [100]AI-Fattani, MA; Douglas, LJ. Penetration of Candida biofilms by antifungal agents [J]. Antimicrobial Agents and Chemotherapy,2004,48(9):3291-3297.
    [101]Garcia-Sanchez, S; Aubert, S; Iraqui, I; Janbon, G; Ghigo, JM; d'Enfert, C. Candida albicans biofilms: a developmental state associated with specific and stable gene expression patterns [J]. Eukaryotic Cell, 2004,3(2):536-545.
    [102]Mukherjee, PK; Chandra, J; Kuhn, DA; Ghannoum, MA. Mechanism of fluconazole resistance in Candida albicans biofilms:Phase-specific role of efflux pumps and membrane sterols [J]. Infection and Immunity,2003,71(8):4333-4340.
    [103]Keren, I; Kaldalu, N; Spoering, A; Wang, YP; Lewis, K. Persister cells and tolerance to antimicrobiALS [J]. Fems Microbiology Letters,2004,230(1):13-18.
    [104]Keren, I; Shah, D; Spoering, A; Kaldalu, N; Lewis, K. Specialized persister cells and the mechanism of multidrug tolerance in Escherichia coli [J]. Journal of Bacteriology,2004,186(24):8172-8180.
    [105]LaFleur, MD; Kumamoto, CA; Lewis, K. Candida albicans biofilms produce antifungal-tolerant persister cells [J]. Antimicrobial Agents and Chemotherapy,2006,50(11):3839-3846.
    [106]Inhibitors of yeast filamentous growth and method of their manufacture; Wang, LH, Ed.; U. S. P. A. Publication:Singapore,2006.
    [107]Staab, JF; Sundstrom, P. Genetic organization and sequence analysis of the hypha-specific cell wall protein gene HWPI of Candida albicans [J]. Yeast,1998,14(7):681-686.
    [108]Staab, JF; Bahn, YS; Tai, CH; Cook, PF; Sundstrom, P. Expression of transglutaminase substrate activity on Candida albicans germ tubes through a coiled, disulfide-bonded N-terminal domain of HWPI requires C-terminal glycosylphosphatidylinositol modification [J]. Journal of Biological Chemistry,2004,279(39):40737-40747.
    [109]Stephens, C. Microbiology:Breaking down biofilms[J]. Current Biology,2002,12(4):R132-R134.
    [110]Ramage, G; Wickes, BL; Lopez-Ribot, JL; Biofilms of Candida albicans and their associated resistance to antifungal agent [J]. Am Clin Lab,2001,20(3.
    [111]Ramage, G; Walle, KV; Wickes, BL; Lopez-Ribot, JL Characteristics of biofilm formation by Candida albicans. [J]. Rev Iberoameric Micologia,2001,18(8.
    [112]Costerton, JW. OVERVIEW OF MICROBIAL BIOFILMS [J]. Journal of Industrial Microbiology,1995, 15(3):137-140.
    [113]Davies, DG; Parsek, MR; Pearson, JP; Iglewski, BH; Costerton, JW; Greenberg, EP. The involvement of cell-to-cell signALS in the development of a bacterial biofilm [J]. Science,1998,280(5361):295-298.
    [114]Parsek, MR; Greenberg, EP In Biofilms,1999; Vol.310; pp 43-55.
    [115]Singh, PK; Schaefer, AL; Parsek, MR; Moninger, TO; Welsh, MJ; Greenberg, EP. Quorum-sensing signALS indicate that cystic fibrosis lungs are infected with bacterial biofilms [J]. Nature,2000, 407(6805):762-764.
    [116]Henriques, M; Martins, M; Azeredo, J; Oliveira, R. Effect of farnesol on Candida dubliniensis morphogenesis [J]. Letters in Applied Microbiology,2007,44(2):199-205.
    [117]Davies, DG; Marques, CNH. A Fatty Acid Messenger Is Responsible for Inducing Dispersion in Microbial Biofilms [J]. Journal of Bacteriology,2009,191(5):1393-1403.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700