Identification of dihydropyrimidine dehydrogenase as a virulence factor essential for the survival ofEntamoeba histolyticain glucose-poor environments

Abstract

SummaryAdaptation to nutritional changes is a key feature for successful survival of a pathogen within its host. The protozoan parasite Entamoeba histolytica normally colonizes the human colon and in rare occasions, this parasite spread to distant organs, such as the liver. E. histolytica obtains most of its energy from the fermentation of glucose into ethanol. In this study, we were intrigued to know how this parasite reacts to changes in glucose availability and we addressed this issue by performing a DNA microarray analysis of gene expression. Results show that parasites that were adapted to growth in absence of glucose increased their virulence and altered the transcription of several genes. One of these genes is the dihydropyrimidine dehydrogenase (DPD), which is involved in degradation of pyrimidines. We showed that this gene is crucial for the parasite's growth when the availability of glucose is limited. These data contribute to our understanding of the parasite's ability to survive in glucosepoor environments and reveal a new role for the DPD enzyme.

N-acetyl ornithine deacetylase is a moonlighting protein and is involved in the adaptation of Entamoeba histolytica to nitrosative stress

“…We and others have previously reported on the parasite’s ability to adapt to various stresses, such as glucose starvation11, serum starvation40 or treatment with metronidazole41. In this report, we inform on the ability of E. histolytica to adapt to NS.…”

“…Recently, we completed a high-throughput proteomic analysis of S-nitrosylated (SNO) proteins in NO-exposed E. histolytica using resin-assisted capture of SNO proteins (SNO-RAC)3, and found that SNO proteins are involved in glycolysis, translation, protein transport, and virulence. It has been reported that E. histolytica can adapt to various stresses910111213. Nevertheless, information on the ability of the parasite to adapt to progressive increases in the intestinal NO concentration, which may occur in patients with inflammation of the large intestine1 or during the establishment of amebiasis14, is lacking.…”

The Entamoeba histolytica Dnmt2 Homolog (Ehmeth) Confers Resistance to Nitrosative Stress

“…The parasite has two stages in its life cycle: the infective cyst and the invasive trophozoite. In the host, the parasite is exposed to various environmental challenges and is capable of adapting to the demands of its surrounding environment, such as extreme changes in the glucose concentration and the oxidative and nitrosative attacks of the host immune system (2)(3)(4)(5).…”

Proteomic profile of the Bradysia odoriphaga in response to the microbial secondary metabolite benzothiazole

“…DPD down-regulation leads to the disruption of normal pyrimidine metabolism. Additionally, DPD is a crucial enzyme for the growth and survival of the parasite under a glucose-limited environment36. Our previous study showed that the carbohydrate content of B. odoriphaga declines after benzothiazole treatment for 6 h14.…”

“…Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the pyrimidine catabolic pathway, in which thymine and uracil are converted into β-alanine or β-aminoisobutyrate using the cofactors NADH or NADPH3536. β-alanine is involved in many metabolic pathways and neurotransmitter functions37.…”