In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-11-15)
Abstract:
The de novo L-cysteine biosynthetic pathway is critical for the growth, antioxidative stress defenses, and pathogenesis of bacterial and protozoan pathogens, such as Salmonella typhimurium and Entamoeba histolytica . This pathway involves two key enzymes, serine acetyltransferase (SAT) and cysteine synthase (CS), which are absent in mammals and therefore represent rational drug targets. The human parasite E . histolytica possesses three SAT and CS isozymes; however, the specific roles of individual isoforms and significance of such apparent redundancy remains unclear. In the present study, we generated E . histolytica cell lines in which CS and SAT expression was knocked down by transcriptional gene silencing. The strain in which CS1 , 2 and 3 were simultaneously silenced and the SAT 3 gene-silenced strain showed impaired growth when cultured in a cysteine lacking BI-S-33 medium, whereas silencing of SAT1 and SAT2 had no effects on growth. Combined transcriptomic and metabolomic analyses revealed that, CS and SAT3 are involved in S-methylcysteine/cysteine synthesis. Furthermore, silencing of the CS1-3 or SAT3 caused upregulation of various iron-sulfur flavoprotein genes. Taken together, these results provide the first direct evidence of the biological importance of SAT3 and CS isoforms in E . histolytica and justify the exploitation of these enzymes as potential drug targets.
Type of Medium:
Online Resource
ISSN:
2045-2322
DOI:
10.1038/s41598-017-15923-3
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2017
detail.hit.zdb_id:
2615211-3
Bookmarklink
