MORAN GP, MACCALLUM DM, SPIERING MJ, COLEMAN DC, SULLIVAN DJ., DIFFERENTIAL REGULATION OF THE TRANSCRIPTIONAL REPRESSOR NRG1 ACCOUNTS FOR ALTERED HOST CELL INTERACTIONS IN CANDIDA ALBICANS AND CANDIDA DUBLINIENSIS, MOLECULAR MICROBIOLOGY, 66, 4, 2007, 915 - 929
MOLECULAR MICROBIOLOGY 66 4
Candida dubliniensis is genetically closely related to C. albicans, but causes fewer
infections in humans and exhibits reduced virulence and filamentation in animal
models of infection. We investigated the role of the C. dubliniensis transcriptional
repressor-encoding gene CdNRG1 in regulating this phenotype. Deletion of both
copies of CdNRG1 increased the formation of true hyphae by C. dubliniensis in
response to serum, exogenous cAMP and CO2. In addition, deletion of CdNRG1
greatly enhanced filamentation and survival of C. dubliniensis in co-culture with
murine macrophages. In the reconstituted human oral epithelium (RHE)
infection model, the nrg1! mutant caused increased tissue damage relative to the
wild-type strain. However, deletion of CdNRG1 did not change the virulence of
C. dubliniensis in the systemic mouse model of infection. The increased rate of
hypha formation in C. albicans relative to C. dubliniensis in response to
phagocytosis by macrophages and serum was associated with rapid
downregulation of NRG1 expression in C. albicans. This study demonstrates that
the reduced virulence of C. dubliniensis is due to the inability of this species to
modulate NRG1 expression in response to the same environmental signals that
promote filamentation in C. albicans.
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