Abstract

The C. glabrata ERG11 gene, encoding the cytochrome P-450-dependent `-14 demethylase, was deleted in order to assess the effect on sterol synthesis, aerobic viability and azole susceptibility. A mutant in which both ERG3 and ERG11 was deleted was aerobically viable and accumulate 14methylfecosterol. A mutant in which only ERG11 was deleted was not aerobically viable but gave rise to an aerobically viable revertant which accumulated both lanosterol and obtusifoliol. This ERG11 mutant had an intact ERG3 gene and increased ERG3 message on Northern analysis. This contrasts with S. cereviseae, in which aerobically viable ERG11 revertants have no functional ERG3 gene. The ERG11 revertant and the ERG3, ERG11 mutant were resistant to azoles, slightly more resistant to amphotericin B and more readily killed by human neutrophils or hydrogen peroxide. We have enrolled four patients in our study of oropharyngeal candidiasis in AIDS patients. One of the four had increased azole resistance in both his C. albicans and C. glabrata isolates at time of relapse. The mechanism by which resistance occurred is under study.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000654-04
Application #
5200552
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Bennett, John E (2009) The changing face of febrile neutropenia-from monotherapy to moulds to mucositis. Management of mycoses in neutropenic patients: a brief history, 1960-2008. J Antimicrob Chemother 63 Suppl 1:i23-6
Greene, Reginald E; Schlamm, Haran T; Oestmann, Jorg-W et al. (2007) Imaging findings in acute invasive pulmonary aspergillosis: clinical significance of the halo sign. Clin Infect Dis 44:373-9
Chen, Kuang-Hua; Miyazaki, Taiga; Tsai, Huei-Fung et al. (2007) The bZip transcription factor Cgap1p is involved in multidrug resistance and required for activation of multidrug transporter gene CgFLR1 in Candida glabrata. Gene 386:63-72
Zonios, Dimitrios I; Falloon, Judith; Huang, Chiung-Yu et al. (2007) Cryptococcosis and idiopathic CD4 lymphocytopenia. Medicine (Baltimore) 86:78-92
Bennett, John E (2006) The debate: a case for randomized controls in invasive aspergillosis. Med Mycol 44 Suppl 1:S305-8
Miyazaki, Taiga; Miyazaki, Yoshitsugu; Izumikawa, Koichi et al. (2006) Fluconazole treatment is effective against a Candida albicans erg3/erg3 mutant in vivo despite in vitro resistance. Antimicrob Agents Chemother 50:580-6
Stevens, Wesley T; Bolan, Charles D; Oblitas, Jaime M et al. (2006) Streptococcus agalactiae sepsis after transfusion of a plateletpheresis concentrate: benefit of donor evaluation. Transfusion 46:649-51
Tsai, Huei-Fung; Krol, Anna A; Sarti, Kelly E et al. (2006) Candida glabrata PDR1, a transcriptional regulator of a pleiotropic drug resistance network, mediates azole resistance in clinical isolates and petite mutants. Antimicrob Agents Chemother 50:1384-92
Miyazaki, Taiga; Tsai, Huei-Fung; Bennett, John E (2006) Kre29p is a novel nuclear protein involved in DNA repair and mitotic fidelity in Candida glabrata. Curr Genet 50:11-22
Bennett, John E (2006) Echinocandins for candidemia in adults without neutropenia. N Engl J Med 355:1154-9

Showing the most recent 10 out of 29 publications