RRC ID 46943
Author Ueno K, Matsumoto Y, Uno J, Sasamoto K, Sekimizu K, Kinjo Y, Chibana H.
Title Intestinal resident yeast Candida glabrata requires Cyb2p-mediated lactate assimilation to adapt in mouse intestine.
Journal PLoS One
Abstract The intestinal resident Candida glabrata opportunistically infects humans. However few genetic factors for adaptation in the intestine are identified in this fungus. Here we describe the C. glabrata CYB2 gene encoding lactate dehydrogenase as an adaptation factor for survival in the intestine. CYB2 was identified as a virulence factor by a silkworm infection study. To determine the function of CYB2, we analysed in vitro phenotypes of the mutant Δcyb2. The Δcyb2 mutant grew well in glucose medium under aerobic and anaerobic conditions, was not supersensitive to nitric oxide which has fungicidal-effect in phagocytes, and had normal levels of general virulence factors protease, lipase and adherence activities. A previous report suggested that Cyb2p is responsible for lactate assimilation. Additionally, it was speculated that lactate assimilation was required for Candida virulence because Candida must synthesize glucose via gluconeogenesis under glucose-limited conditions such as in the host. Indeed, the Δcyb2 mutant could not grow on lactate medium in which lactate is the sole carbon source in the absence of glucose, indicating that Cyb2p plays a role in lactate assimilation. We hypothesized that Cyb2p-mediated lactate assimilation is necessary for proliferation in the intestinal tract, as the intestine is rich in lactate produced by bacteria flora, but not glucose. The Δcyb2 mutant showed 100-fold decreased adaptation and few cells of Saccharomyces cerevisiae can adapt in mouse ceca. Interestingly, C. glabrata could assimilate lactate under hypoxic conditions, dependent on CYB2, but not yeast S. cerevisiae. Because accessible oxygen is limited in the intestine, the ability for lactate assimilation in hypoxic conditions may provide an advantage for a pathogenic yeast. From those results, we conclude that Cyb2p-mediated lactate assimilation is an intestinal adaptation factor of C. glabrata.
Volume 6(9)
Pages e24759
Published 2011-1-1
DOI 10.1371/journal.pone.0024759
PII PONE-D-11-06791
PMID 21931845
PMC PMC3170380
MeSH Animals Bombyx / microbiology Candida glabrata / genetics Candida glabrata / growth & development* Candida glabrata / metabolism* Candida glabrata / pathogenicity Fungal Proteins / genetics Fungal Proteins / metabolism* Intestines / microbiology* Lactic Acid / metabolism* Mice Mutation Nitric Oxide / pharmacology Virulence / genetics Virulence / physiology*
IF 2.74
Times Cited 58
Pathogenic microorganisms NA