Molecular and phenotypic analysis of mutations causing anionic phospholipid deficiency in closely related yeast species

Abstract

The pel1 mutation in Saccharomyces cerevisiae and the Cgpgs1Delta mutation in Candida glabrata result in deficiency of mitochondrial phosphatidylglycerolphosphate synthase and lack of two anionic phospholipids, phosphatidylglycerol and cardiolipin. DNA sequence analysis of the PCR-amplified pel1 mutant allele revealed that the pel1 mutation resulted from a single amino-acid substitution (Glu(463)Lys) in the C-terminal part of encoded enzyme. The CgPGS1 gene cloned in a centromeric pFL38 vector functionally complemented the pel1 mutation in S. cerevisiae. Likewise, the ScPGS1 gene cloned in pCgACU5 plasmid fully complemented the Cgpgs1Delta mutation in C. glabrata. This mutation increased the cell surface hydrophobicity and decreased biofilm formation. These results support a close evolutionary relatedness of S. cerevisiae and C. glabrata and point to the relationship between expression of virulence factors and anionic phospholipid deficiency in pathogenic C. glabrata.

Analysis of sphingolipids, sterols, and phospholipids in human pathogenic Cryptococcus strains

“…CDP-DAG is converted into PI by the activity of three enzymes: L-myo-inositol-1-phosphate synthase (Ino1 in S. cereviseae), inositol monophosphatase (Inm1 in S. cereviseae), PI synthase (Pis1 in S. cereviseae) (74,79). CDP-DAG is converted into PG by phosphatidylglycerolphosphate synthase [Pgs1 in S. cereviseae (80) and C. glabrata (81)] and a phosphatidylglycerophosphatase [Gep4 in S. cereviseae (82)]. PE is converted to LPE by phospholipase B [Plb1 in C. gattii (83)].…”

The Lack of SNARE Protein Homolog Syn8 Influences Biofilm Formation of Candida glabrata

“…SNF2 and SNF6 gene disruption mutants also exhibit poor ability to form biofilms (Riera et al, 2012). Pgs1p is a phosphatidylglycerol phosphate synthase, and it has been reported that deletion of the PGS1 gene results in increased cell surface hydrophobicity and decreased biofilm formation of C. glabrata (Bat'ová et al, 2009). In addition to proteins that act on cell wall synthesis related to the adhesion step during biofilm formation, some recent studies have reported that the multidrug resistance transporters Pdr16p and Tpo1_2p contribute to azole resistance and are related to biofilm formation (Culakova et al, 2013;Santos et al, 2017).…”