Differentiation of Leishmania donovani in host-free system: analysis of signal perception and response

Barak, Eran Cohen; Amin-Spector, Sigal; Gerliak, Elena; Goyard, Sophie; Holland, Neta; Zilberstein, Dan

doi:10.1016/j.molbiopara.2005.02.004

Cited by 149 publications

(172 citation statements)

References 35 publications

Supporting

Mentioning

155

Contrasting

Unclassified

Order By: Relevance

“…S-azetidine-2-carboxylic acid is a non-natural amino acid that has chemical and biochemical applications [41][42][43][44][45][46] ͓see Fig. 2͑a͔͒.…”

Section: S-azetidine-2-carboxylic Acidmentioning

confidence: 99%

Using the ONIOM hybrid method to apply equation of motion CCSD to larger systems: Benchmarking and comparison with time-dependent density functional theory, configuration interaction singles, and time-dependent Hartree–Fock

Caricato

Vreven

Trucks

et al. 2009

The Journal of Chemical Physics

View full text Add to dashboard Cite

Assessment of time-dependent density functional schemes for computing the oscillator strengths of benzene, phenol, aniline, and fluorobenzene J. Chem. Phys. 127, 084103 (2007) Equation of motion coupled-cluster singles and doubles ͑EOM-CCSD͒ is one of the most accurate computational methods for the description of one-electron vertical transitions. However, its O͑N 6 ͒ scaling, where N is the number of basis functions, often makes the study of molecules larger than 10-15 heavy atoms prohibitive. In this work we investigate how accurately less expensive methods can approximate the EOM-CCSD results. We focus on our own N-layer integrated molecular orbital molecular mechanics ͑ONIOM͒ hybrid scheme, where the system is partitioned into regions which are treated with different levels of theory. For our set of benchmark calculations, the comparison of conventional configuration interaction singles ͑CIS͒, time-dependent Hartree-Fock ͑TDHF͒, and time-dependent density functional theory ͑TDDFT͒ methods and ONIOM ͑with different low level methods͒ showed that the best accuracy-computational time combination is obtained with ONIOM͑EOM:TDDFT͒, which has a rms of the error with respect to the conventional EOM-CCSD of 0.06 eV, compared with 0.47 eV of the conventional TDDFT.

show abstract

“…S-azetidine-2-carboxylic acid is a non-natural amino acid that has chemical and biochemical applications [41][42][43][44][45][46] ͓see Fig. 2͑a͔͒.…”

Section: S-azetidine-2-carboxylic Acidmentioning

confidence: 99%

Using the ONIOM hybrid method to apply equation of motion CCSD to larger systems: Benchmarking and comparison with time-dependent density functional theory, configuration interaction singles, and time-dependent Hartree–Fock

Caricato

Vreven

Trucks

et al. 2009

The Journal of Chemical Physics

View full text Add to dashboard Cite

show abstract

“…The differentiation process can be mimicked in axenic culture by shifting promastigotes from an insect-like (26°C, pH 7) to an intralysosomal-like (37°C, pH 5.5 and 5% CO 2 ) environment [15][16][17][18][19]. These axenic amastigotes resemble animal-derived amastigotes and have been widely used for investigating parasites activities without the complication of host cell material [20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

“…These axenic amastigotes resemble animal-derived amastigotes and have been widely used for investigating parasites activities without the complication of host cell material [20][21][22][23]. Time-course analysis of L. donovani differentiation showed that promastigotes expressed the amastigote-specific A2 protein family within an hour of exposure to the intralysosomal environment and at five hours they start to transform to amastigote-shaped cells [19]. This morphological transformation occurs synchronously, while the cells are arrested at the G1 stage of the cell cycle, and is complete within 24 hrs.…”

Section: Introductionmentioning

confidence: 99%

Analysis of the Leishmania donovani transcriptome reveals an ordered progression of transient and permanent changes in gene expression during differentiation

Saxena

Lahav

Holland

et al. 2007

Molecular and Biochemical Parasitology

148

140

View full text Add to dashboard Cite

Leishmania donovani is an intracellular protozoan parasite that causes kala-azar in humans. During infection the extracellular insect forms (promastigotes) undergo rapid differentiation to intracellular amastigotes that proliferates in phagolysosomes of mammalian macrophages. We used microarraybased expression profiling to investigate the time-course of changes in RNA abundance during promastigote-to-amastigote differentiation in a host-free system that mimics this process. These studies revealed that several hundred genes underwent an ordered progression of transient or permanent up-and down-regulation during differentiation. Genes that were permanently upregulated in amastigotes were enriched for transporters and surface proteins, but under-represented in genes involved in protein and other metabolism. Most of these changes occurred late in the differentiation process, when morphological differentiation was essentially complete. Downregulated genes were over-represented in those involved in cell motility, growth and/or maintenance, and these changes generally occurred earlier in the process. Genes that were transiently up-or downregulated during differentiation included those encoding heat shock proteins, ubiquitin hydrolases, RNA binding proteins, protein kinases, a protein phosphatase, and a histone deacetylase. These results suggest that changes in mRNA abundance may be important in signal transduction, as well as protein and mRNA turnover, during differentiation. In addition to these mRNA changes, other transcripts including one or more rRNAs and snoRNAs, and non-coding RNAs from several telomeres, also showed substantial changes in abundance during the differentiation process. This paper provides the first genome-scale quantitative analysis of gene expression during the transition from promastigotes to amastigotes and demonstrates the utility of the host-free differentiation system.

show abstract

“…Briefly, differentiation of promastigote towards axenic amastigote was induced by a combination of 37°C cultivation and a time-coordinated acidification of the culture medium to pH 5.5 (Doyle et al 1991;Castilla et al 1995;Gupta et al 1996;Saar et al 1998;Barak et al 2005). Axenic amastigotes were cultured at 37°C with 5% CO 2 .…”

Section: In Vitro Stage Differentiationmentioning

confidence: 99%

“…Simplified, an increase of cultivation temperature and a subsequent acidification suffice to trigger promastigote-to-amastigote conversion under axenic culture conditions. This allows the study of stage conversion and of the so-called axenic amastigotes in a biochemically well-defined context (Zilberstein and Shapira 1994;Barak et al 2005;Clos 2007). …”

Section: Introductionmentioning

confidence: 99%

The co-chaperone SGT of Leishmania donovani is essential for the parasite's viability

Ommen

Chrobak

Clos

2010

Cell Stress and Chaperones

View full text Add to dashboard Cite

Molecular chaperone proteins play a pivotal role in the protozoan parasite Leishmania donovani, controlling cell fate and ensuring intracellular survival. In higher eukaryotes, the so-called co-chaperone proteins are required for client protein recognition and proper function of chaperones, among them the small glutamine-rich tetratricopeptide repeat proteins (SGT) which interact with both HSP70 and HSP90 chaperones. An atypical SGT homolog is found in the L. donovani genome, encoding a protein lacking the C-terminal glutamine-rich region, normally typical for SGT family members. The gene is expressed constitutively during the life cycle and is essential for survival and/or growth of the parasites. LdSGT forms large, stable complexes that also include another putative cochaperone, HSC70 interacting protein (HIP). The gene product forms cytoplasmic clusters, matching the subcellular distribution of HIP and partly that of the major cytoplasmic chaperones, HSP70 and HSP90, reflecting a direct molecular interaction with both chaperones.

show abstract

Differentiation of Leishmania donovani in host-free system: analysis of signal perception and response

Cited by 149 publications

References 35 publications

Using the ONIOM hybrid method to apply equation of motion CCSD to larger systems: Benchmarking and comparison with time-dependent density functional theory, configuration interaction singles, and time-dependent Hartree–Fock

Using the ONIOM hybrid method to apply equation of motion CCSD to larger systems: Benchmarking and comparison with time-dependent density functional theory, configuration interaction singles, and time-dependent Hartree–Fock

Analysis of the Leishmania donovani transcriptome reveals an ordered progression of transient and permanent changes in gene expression during differentiation

The co-chaperone SGT of Leishmania donovani is essential for the parasite's viability

Contact Info

Product

Resources

About