| Autor: |
Stock, Stephen D., Hama, Hiroko, Radding, Jeffrey A., Young, Debra A., Takemoto, Jon Y. |
| Zdroj: |
Antimicrobial Agents and Chemotherapy; May 2000, Vol. 44 Issue: 5 p1174-1180, 7p |
| Abstrakt: |
ABSTRACTSyringomycin E is an antifungal cyclic lipodepsinonapeptide that inhibits the growth of Saccharomyces cerevisiaeby interaction with the plasma membrane. A screen conducted to find the yeast genes necessary for its fungicidal action identified two novel syringomycin E response genes, SYR3and SYR4. Asyr3mutant allele was complemented by ELO2andELO3. These genes encode enzymes that catalyze the elongation of sphingolipid very long chain fatty acids. Tetrad analysis showed that SYR3was ELO2. Strains with deletions of SYR3/ELO2and ELO3were resistant to syringomycin E, and lipid analyses of both mutants revealed shortened fatty acid chains and lower levels of sphingolipids.SYR4was identified by Tn5inactivation of genomic library plasmids that complemented a syr4mutant allele. SYR4was found to be identical to IPT1, which encodes the terminal sphingolipid biosynthetic enzyme, mannosyl-diinositolphosphoryl-ceramide synthase. Deletion Δsyr4/ipt1strains were viable, were resistant to syringomycin E, did not produce mannosyl-diinositolphosphoryl-ceramide, and accumulated mannosyl-inositolphosphoryl-ceramide. Accumulation of mannosyl-inositolphosphoryl-ceramide was not responsible for resistance since a temperature-sensitive secretory pathway mutant (sec14-3ts) accumulated this sphingolipid and was sensitive to syringomycin E. Finally, Δcsg1/sur1and Δcsg2strains defective in the transfer of mannose to inositolphosphoryl-ceramide were resistant to syringomycin E. These findings show that syringomycin E growth inhibition of yeast is promoted by the production of sphingolipids with fully elongated fatty acid chains and the mannosyl and terminal phosphorylinositol moieties of the polar head group. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
