Journal of Antimicrobial Chemotherapy (2001) 47, 527-536
© 2001 The British Society for Antimicrobial Chemotherapy
Mechanisms of fluconazole resistance in Candida albicans isolates from Japanese AIDS patients
a Teikyo University Institute of Medical Mycology, 359 Otsuka, Hachioji, Tokyo 192-0395, Japan; b Molecular Microbiology Laboratory, Department of Oral Sciences and Orthodontics, School of Dentistry, University of Otago, PO Box 647, Dunedin, New Zealand; c Department of Mycology, Nippon Roche Research Center, 200 Kajiwara, Kamakura, Kanagawa 247-0063, Japan
Four Candida albicans isolates, TIMM 3163, TIMM 3164, TIMM 3165 and TIMM 3166, with reduced fluconazole susceptibility were obtained from three AIDS patients in Japan, and the mechanisms of their drug resistance were studied. All isolates showed lower levels of intracellular accumulation of fluconazole than ATCC 10231, a susceptible control strain of C. albicans. Increased amounts of CDR1 and CDR2 mRNA encoding putative ATP binding cassette (ABC) transporters were associated with the azole resistance of all TIMM isolates, apart from TIMM 3164. In addition, increased Cdr1p levels were immunodetected in the cell membrane fractions of all the TIMM strains except for TIMM 3164. Gene amplification was not responsible for CDR1 overexpression and there were no significant differences in the mRNA levels of CDR3 or CDR4 (ABC transporters) in the azole-susceptible and -resistant cells. CaMDR1 (a major facilitator superfamily) gene expression was not observed in any of the resistant isolates or the control strain. These results suggest that energy-dependent drug efflux associated with increased expression of CDR1 and CDR2 is involved in the fluconazole resistance mechanisms in two of the four isolates, TIMM 3165 and TIMM 3166. TIMM 3164 demonstrated energy-dependent drug efflux without overexpression of CDR1-4 or CaMDR1, indicating that some other pump may be operating. Despite showing low levels of drug efflux and overexpression of CDR1 and CDR2, efflux in TIMM 3163 was not energy dependent, suggesting that the expressed Cdr1p non-functional Cdr1p and that other resistance mechanisms may operate in this strain.
* Tel: +81-45-545-3178; Fax: +81-45-541-2359; E-mail: Kazunori_Maebashi{at}meiji.co.jp
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. D. Cannon, E. Lamping, A. R. Holmes, K. Niimi, P. V. Baret, M. V. Keniya, K. Tanabe, M. Niimi, A. Goffeau, and B. C. Monk Efflux-Mediated Antifungal Drug Resistance Clin. Microbiol. Rev., April 1, 2009; 22(2): 291 - 321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Tsao, F. Rahkhoodaee, and M. Raymond Relative Contributions of the Candida albicans ABC Transporters Cdr1p and Cdr2p to Clinical Azole Resistance Antimicrob. Agents Chemother., April 1, 2009; 53(4): 1344 - 1352. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Holmes, Y.-H. Lin, K. Niimi, E. Lamping, M. Keniya, M. Niimi, K. Tanabe, B. C. Monk, and R. D. Cannon ABC Transporter Cdr1p Contributes More than Cdr2p Does to Fluconazole Efflux in Fluconazole-Resistant Candida albicans Clinical Isolates Antimicrob. Agents Chemother., November 1, 2008; 52(11): 3851 - 3862. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Niimi, K. Maki, F. Ikeda, A. R. Holmes, E. Lamping, M. Niimi, B. C. Monk, and R. D. Cannon Overexpression of Candida albicans CDR1, CDR2, or MDR1 Does Not Produce Significant Changes in Echinocandin Susceptibility. Antimicrob. Agents Chemother., April 1, 2006; 50(4): 1148 - 1155. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Tanida, T. Okamoto, E. Ueta, T. Yamamoto, and T. Osaki Antimicrobial peptides enhance the candidacidal activity of antifungal drugs by promoting the efflux of ATP from Candida cells J. Antimicrob. Chemother., January 1, 2006; 57(1): 94 - 103. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pancholi, S. Park, D. Perlin, C. Kubin, and P. Della-Latta Molecular Characterization of Fluconazole Resistance in a Case of Candida albicans Ocular Infection J. Clin. Microbiol., December 1, 2004; 42(12): 5938 - 5939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Niimi, K. Niimi, Y. Takano, A. R. Holmes, F. J. Fischer, Y. Uehara, and R. D. Cannon Regulated overexpression of CDR1 in Candida albicans confers multidrug resistance J. Antimicrob. Chemother., December 1, 2004; 54(6): 999 - 1006. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Pinjon, G. P. Moran, C. J. Jackson, S. L. Kelly, D. Sanglard, D. C. Coleman, and D. J. Sullivan Molecular Mechanisms of Itraconazole Resistance in Candida dubliniensis Antimicrob. Agents Chemother., August 1, 2003; 47(8): 2424 - 2437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Riou, F. Guegnard, Y. Le Vern, and D. Kerboeuf Modulation of the multidrug resistance (MDR) system in the nematode Haemonchus contortus by changing cholesterol content: effects on resistance to anthelmintics J. Antimicrob. Chemother., August 1, 2003; 52(2): 180 - 187. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Niewerth, D. Kunze, M. Seibold, M. Schaller, H. C. Korting, and B. Hube Ciclopirox Olamine Treatment Affects the Expression Pattern of Candida albicans Genes Encoding Virulence Factors, Iron Metabolism Proteins, and Drug Resistance Factors Antimicrob. Agents Chemother., June 1, 2003; 47(6): 1805 - 1817. [Abstract] [Full Text] [PDF]
|
|