Global gene expression in Leishmania

Cohen-Freue, G.; Holzer, Timothy R.; Forney, James D.; McMaster, W. Robert

doi:10.1016/j.ijpara.2007.04.011

Cited by 110 publications

(107 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…3E and F). This is consistent with many previous reports showing that elevated temperature and/or acidic pH induced the mRNA expression of several stress-responsive genes, including LdApx and sHSP20 (1,(25)(26)(27), favored by reduced translation during amastigote differentiation, allowing parasites to conserve energy while reconfiguring the expression of specific sets of genes necessary for their survival in the mammalian host (28). It has been shown that elevated temperature and acidic pH induce the phosphorylation of eIF2␣ and trigger the differentiation of L. infantum by decreasing global translation and enhancing the relative expression levels of stress-responsive proteins, enabling the parasite to adapt according to persisting physiological conditions inside the phagolysosomal compartment of host macrophages …”

Section: Discussionsupporting

confidence: 93%

Phosphorylation of Translation Initiation Factor 2-Alpha in Leishmania donovani under Stress Is Necessary for Parasite Survival

Abhishek

Sardar

Das

et al. 2017

Molecular and Cellular Biology

View full text Add to dashboard Cite

The transformation of Leishmania donovani from a promastigote to an amastigote during mammalian host infection displays the immense adaptability of the parasite to survival under stress. Induction of translation initiation factor 2-alpha (eIF2␣) phosphorylation by stress-specific eIF2␣ kinases is the basic stress-perceiving signal in eukaryotes to counter stress. Here, we demonstrate that elevated temperature and acidic pH induce the phosphorylation of Leishmania donovani eIF2␣ (LdeIF2␣). In vitro inhibition experiments suggest that interference of LdeIF2␣ phosphorylation under conditions of elevated temperature and acidic pH debilitates parasite differentiation and reduces parasite viability (P Ͻ 0.05). Furthermore, inhibition of LdeIF2␣ phosphorylation significantly reduced the infection rate (P Ͻ 0.05), emphasizing its deciding role in successful invasion and infection establishment. Notably, our findings suggested the phosphorylation of LdeIF2␣ under H 2 O 2 -induced oxidative stress. Inhibition of H 2 O 2 -induced LdeIF2␣ phosphorylation hampered antioxidant balance by impaired redox homeostasis gene expression, resulting in increased reactive oxygen species accumulation (P Ͻ 0.05) and finally leading to decreased parasite viability (P Ͻ 0.05). Interestingly, exposure to sodium antimony glucamate and amphotericin B induces LdeIF2␣ phosphorylation, indicating its possible contribution to protection against antileishmanial drugs in common use. Overall, the results strongly suggest that stress-induced LdeIF2␣ phosphorylation is a necessary event for the parasite life cycle under stressed conditions for survival.

show abstract

Section: Discussionsupporting

confidence: 93%

Phosphorylation of Translation Initiation Factor 2-Alpha in Leishmania donovani under Stress Is Necessary for Parasite Survival

Abhishek

Sardar

Das

et al. 2017

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…6 Control of gene expression does not occur at the transcriptional level but rather at the level of RNA stability, translation and protein turnover. 7 Typical promoter elements for protein expressing genes have not been identified, and transcription occurs processively over long stretches in a single direction. 8,9 However, strand switch regions appear to function similarly to promoters and techniques have been developed that simultaneously assemble multiple DNA fragments and considerably simplify the assembly of targeting constructs.…”

Section: Leishmania Geneticsmentioning

confidence: 99%

The genetic toolbox forLeishmaniaparasites

Roberts

2011

Bioengineered Bugs

View full text Add to dashboard Cite

“…So far, a variety of microarray analyses between diverse Leishmania samples revealed only small differences in expression profiling. Microarray ana-lyses between procyclic and metacyclic promastigotes have revealed that only 1 to 2% of the genes (slides scoring ~7000 genes) are modulated by a 2-fold or larger factor in all studied conditions [100]. Preferential stage-specific genes constitute only ~0.2-5 % of the expressed genome (8160 genes surveyed) when analyzing promastigote and amastigote transcriptomes [98,101].…”

Section: Transcriptome and Proteomementioning

confidence: 99%

“…Therefore, stage-specific genes are poorly represented in microarray analysis as shown for several Leishmania species (e.g. L. (L.) donovani axenic amastigotes: 5.5%) [100]. Altogether, most of the up-regulated genes are found in promastigotes.…”

Section: Transcriptome and Proteomementioning

confidence: 99%

Using Genomic Information to Understand Leishmania Biology

Toledo¹

2010

TOPARAJ

View full text Add to dashboard Cite

Abstract:The genomes of different species of Leishmania have been deciphered in recent years. We learned that the genome content and organization of Leishmania major, Leishmania braziliensis and Leishmania infantum are highly similar and annotation of these genomes revealed that there are few species-specific genes. Association of genome information with reverse and forward genetics approaches allows posing and answering relevant biological questions in a novel way. In this article we briefly present an overview of relevant aspects of genome organization of the Leishmania and how this information can be used to improve our understanding of the biology, pathogenesis, host-parasite interaction issues. We present some of the most useful bioinformatics tools/softwares, which are currently available and how each one of them can be used to explore the genome supporting a wide variety of queries. We included other computational tools which allow integrating the genome data with biochemical pathways revealing metabolic and regulatory networks to be investigated. Finally, we discuss reverse and forward genetic tools available and finalize with considerations on established and novel high-throughput approaches at the genome, transcriptome and proteome levels.

show abstract

Global gene expression in Leishmania

Cited by 110 publications

References 40 publications

Phosphorylation of Translation Initiation Factor 2-Alpha in Leishmania donovani under Stress Is Necessary for Parasite Survival

Phosphorylation of Translation Initiation Factor 2-Alpha in Leishmania donovani under Stress Is Necessary for Parasite Survival

The genetic toolbox forLeishmaniaparasites

Using Genomic Information to Understand Leishmania Biology

Contact Info

Product

Resources

About