AI Article Synopsis
- Acanthamoeba spp. cause serious infections in humans, and understanding cysteine and serine metabolism is essential for comprehension of their energy metabolism.
- Researchers amplified genes for cysteine synthase (AcCS), phosphoglycerate dehydrogenase (AcGDH), and phosphoserine aminotransferase (AcSPAT), expressing them in bacteria for further study.
- The study confirms AcCS's role in cysteine production and highlights that AcGDH and AcSPAT are involved in serine degradation, suggesting how these metabolic pathways could be targeted for therapeutic interventions against Acanthamoeba infections.
Article Abstract
Background: Acanthamoeba spp. can cause serious human infections, including Acanthamoeba keratitis, granulomatous amoebic encephalitis and cutaneous acanthamoebiasis. Cysteine biosynthesis and the L-serine metabolic pathway play important roles in the energy metabolism of Acanthamoeba spp. However, no study has confirmed the functions of cysteine synthase (AcCS) in the cysteine pathway and phosphoglycerate dehydrogenase (AcGDH) or phosphoserine aminotransferase (AcSPAT) in the non-phosphorylation serine metabolic pathway of Acanthamoeba.
Methods: The AcCS, AcGDH and AcSPAT genes were amplified by PCR, and their recombinant proteins were expressed in Escherichia coli. Polyclonal antibodies against the recombinant proteins were prepared in mice and used to determine the subcellular localisation of each native protein by confocal laser scanning microscopy. The enzymatic activity of each recombinant protein was also analysed. Furthermore, each gene expression level was analysed by quantitative PCR after treatment with different concentrations of cysteine or L-serine.
Results: The AcCS gene encodes a 382-amino acid protein with a predicted molecular mass of 43.1 kDa and an isoelectric point (pI) of 8.11. The AcGDH gene encodes a 350-amino acid protein with a predicted molecular mass of 39.1 kDa and a pI of 5.51. The AcSPAT gene encodes a 354-amino acid protein with a predicted molecular mass of 38.3 kDa and a pI of 6.26. Recombinant AcCS exhibited a high cysteine synthesis activity using O-acetylserine and NaS as substrates. Both GDH and SPAT catalysed degradation, rather than synthesis, of serine. Exogenous L-serine or cysteine inhibited the expression of all three enzymes in a time- and dose-dependent manner.
Conclusions: This study demonstrated that AcCS participates in cysteine biosynthesis and serine degradation via the non-phosphorylation serine metabolic pathway, providing a molecular basis for the discovery of novel anti-Acanthamoeba drugs.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6257972 | PMC |
| http://dx.doi.org/10.1186/s13071-018-3188-7 | DOI Listing |
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