Expression of glyceraldehyde 3-phosphate dehydrogenase is enhanced in Leishmania spp naturally resistant to nitric oxide

Rios, M.; Silva, W. R. T.; Azevedo, Alana Freire de; Santos, Priscila Lima dos; Teixeira, Simone Aparecida; Muscará, Marcelo Nícolas; Thomazzi, Sara Maria; Almeida, Roque Pacheco de; Fernandes, Roberta Pereira Miranda; Scher, Ricardo

doi:10.4238/2015.june.29.4

Cited by 7 publications

(5 citation statements)

References 18 publications

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“…GAPDH expression is increased in Leishmania spp. that are naturally resistant to NS35 which suggest that GAPDH has a protective role against NS in this parasite. In contrast GAPDH can trigger cell death in oxidatively- and nitrosatively-stressed mammalian cells363738.…”

Section: Resultsmentioning

confidence: 97%

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

Shahi

Trebicz-Geffen

Nagaraja

et al. 2016

Sci Rep

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Adaptation of the Entamoeba histolytica parasite to toxic levels of nitric oxide (NO) that are produced by phagocytes may be essential for the establishment of chronic amebiasis and the parasite’s survival in its host. In order to obtain insight into the mechanism of E. histolytica’s adaptation to NO, E. histolytica trophozoites were progressively adapted to increasing concentrations of the NO donor drug, S-nitrosoglutathione (GSNO) up to a concentration of 110 μM. The transcriptome of NO adapted trophozoites (NAT) was investigated by RNA sequencing (RNA-seq). N-acetyl ornithine deacetylase (NAOD) was among the 208 genes that were upregulated in NAT. NAOD catalyzes the deacetylation of N-acetyl-L-ornithine to yield ornithine and acetate. Here, we report that NAOD contributes to the better adaptation of the parasite to nitrosative stress (NS) and that this function does not depend on NAOD catalytic activity. We also demonstrated that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is detrimental to E. histolytica exposed to NS and that this detrimental effect is neutralized by NAOD or by a catalytically inactive NAOD (mNAOD). These results establish NAOD as a moonlighting protein, and highlight the unexpected role of this metabolic enzyme in the adaptation of the parasite to NS.

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Section: Resultsmentioning

confidence: 97%

“…On the one hand, upregulation of GAPDH expression is correlated with resistance to NS in Leishmania spp 35. and it has been proposed that GAPDH may act as a NO scavenger62.…”

Section: Discussionmentioning

confidence: 99%

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

Shahi

Trebicz-Geffen

Nagaraja

et al. 2016

Sci Rep

View full text Add to dashboard Cite

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“…The interpretation of the results and comparison between studies should also consider similar species of Leishmania and life stage, such as promastigote or amastigote forms of the parasite, since different species of the parasite and evolutionary forms have specific biological characteristics that can produce discordant results [ 42 , 43 , 44 ]. In addition, the results are dependent on the experimental model being used [ 38 ].…”

Section: Resultsmentioning

confidence: 99%

Leishmanicidal Activity and Structure-Activity Relationships of Essential Oil Constituents

et al. 2017

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Several constituents of essential oils have been shown to be active against pathogens such as bacteria, fungi, and protozoa. This study demonstrated the in vitro action of ten compounds present in essential oils against Leishmania amazonensis promastigotes. With the exception of p-cymene, all evaluated compounds presented leishmanicidal activity, exhibiting IC50 between 25.4 and 568.1 μg mL−1. Compounds with the best leishmanicidal activity presented a phenolic moiety (IC50 between 25.4 and 82.9 μg mL−1). Alicyclic alcohols ((−)-menthol and isoborneol) and ketones ((−)-carvone) promoted similar activity against the parasite (IC50 between 190.2 and 198.9 μg mL−1). Most of the compounds showed low cytotoxicity in L929 fibroblasts. Analysis of the structure-activity relationship of these compounds showed the importance of the phenolic structure for the biological action against the promastigote forms of the parasite.

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“…It also contributes to parasite infectivity, as evidenced by its abundant expression in Sb- and AmB-resistant Leishmania parasites [ 23 , 86 , 87 ], and the protein glycerol-3-phosphate dehydrogenase (glycosomal) (GAPDH). Changes in GAPDH expression may be responsible, at least in part, for the natural resistance to nitric oxide reported in human and canine leishmaniasis [ 88 ]. We also located the dihydroxyacetone kinase 1-like protein, which is important for growth and survival and essential for virulence [ 89 ].…”

Section: Resultsmentioning

confidence: 99%

Transcriptome Analysis of Intracellular Amastigotes of Clinical Leishmania infantum Lines from Therapeutic Failure Patients after Infection of Human Macrophages

et al. 2022

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Leishmaniasis is considered to be one of the most neglected tropical diseases affecting humans and animals around the world. Due to the absence of an effective vaccine, current treatment is based on chemotherapy. However, the continuous appearance of drug resistance and therapeutic failure (TF) lead to an early obsolescence of treatments. Identification of the factors that contribute to TF and drug resistance in leishmaniasis will constitute a useful tool for establishing future strategies to control this disease. In this manuscript, we evaluated the transcriptomic changes in the intracellular amastigotes of the Leishmania infantum parasites isolated from patients with leishmaniasis and TF at 96 h post-infection of THP-1 cells. The adaptation of the parasites to their new environment leads to expression alterations in the genes involved mainly in the transport through cell membranes, energy and redox metabolism, and detoxification. Specifically, the gene that codes for the prostaglandin f2α synthase seems to be relevant in the pathogenicity and TF since it appears substantially upregulated in all the L. infantum lines. Overall, our results show that at the late infection timepoint, the transcriptome of the parasites undergoes significant changes that probably improve the survival of the Leishmania lines in the host cells, contributing to the TF phenotype as well as drug therapy evasion.

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Expression of glyceraldehyde 3-phosphate dehydrogenase is enhanced in Leishmania spp naturally resistant to nitric oxide

Cited by 7 publications

References 18 publications

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

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

Leishmanicidal Activity and Structure-Activity Relationships of Essential Oil Constituents

Transcriptome Analysis of Intracellular Amastigotes of Clinical Leishmania infantum Lines from Therapeutic Failure Patients after Infection of Human Macrophages

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