Non-fatal Candida albicans cph1/cph1 efg1/efg1 transcription factor mutants forming filaments and causing inflammation in a mouse model of systemic infection.
Chia Geun Chen (1), Yun Liang Yang (2), Hsiao Hsu Cheng (1), Chia Li Su (1), Shiu Feng Huang (3), Chiung Tong Chen (4), Yu Tien Liu (5), Ih Jen Su (1), Hsiu Jung Lo (1)
(1) Division of Clinical Research, NHRI, 35 Keyan Road, Miaoli County, 350, Taiwan; (2) Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan; (3) Division of Molecular & Genomic Medicine, NHRI, Miaoli County; (4) Division of Biotechnology & Pharmaceutical Research, NHRI, Miaoli County, Taiwan; (5) Depertment of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan
The cph1/cph1 efg1/efg1 Candida albicans mutant cells failed to form filaments and were defective in invasion under standard conditions in culture media and also were non-fatal in a mouse model of systemic infection. Homogenates of kidneys from the mice infected with the wild-type cells and the mutant cells yielded a mean of 2.1 x 10 7 CFU/g and 2.2 x 10 6 CFU/g, respectively. The kidneys from the mice infected with the wild-type cells showed extensive renal cortical necrosis associated with neutrophilic infiltration, among which abundant wild-type hyphal cells were detected. Hence, tubular necrosis leading to renal failure in the mice injected with the wild-type cells may be the cause of death. The kidneys from the mice infected with the mutant cells showed only mild and focal inflammation in the cortical region without tissue necrosis. Despite that the cph1/cph1 efg1/efg1 mutant cells formed filaments in vivo, the mutant cells were present mainly in the renal pelvic cavity and no Candida cell was detected in the inflammatory region of the renal parenchyma. The cph1/cph1 efg1/efg1 mutant cells were sufficient to induce host inflammation but were unable to invade sufficiently to kill the host. Base on these observations, we conclude that filamentous growth per se is not sufficient to be fatal in the mouse model. Thus, the genes unrelated to cell morphology but regulated by Cph1 and/or Efg1 are also required for virulence.