Quantitative proteomic analysis of amastigotes from Leishmania (L.) amazonensis LV79 and PH8 strains reveals molecular traits associated with the virulence phenotype

Rezende, Eloiza de; Kawahara, Rebeca; Peña, Mauricio S.; Palmisano, Giuseppe; Stolf, Beatriz S.

doi:10.1371/journal.pntd.0006090

Cited by 23 publications

(36 citation statements)

References 55 publications

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“…Comparison of the 4E2(+/-) proteome with published amastigote proteomes. The proteome of upregulated 4E2(+/-) mutant promastigotes was compared with the proteins enriched in the amastigote proteome of virulent L. amazonensis PH8 strain, as compared to the less virulent LV79 [57].…”

Section: Legends To Supplemental Materialsmentioning

confidence: 99%

Distinct features of theLeishmaniacap-binding protein LeishIF4E2 revealed by CRISPR-Cas9 mediated heterozygous deletion

Baron

Tupperwar

Davidov

et al. 2020

Preprint

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20 Leishmania parasites cycle between sand-fly vectors and mammalian hosts, adapting to 21 alternating environments by stage-differentiation, accompanied by changes in the proteome 22 profiles. Translation regulation plays a central role in driving the differential program of gene 23 expression, since control of gene regulation in Leishmania is mostly post-transcriptional. 24 The Leishmania genome encodes six eIF4E candidates, each assumed to have specific functions, 25 although overlaps are expected. It is noted that some of them can bind to a dedicated eIF4G 26 candidate partners, and LeishIF4E2 does not bind any known eIF4G ortholog. LeishIF4E2 was 27 previously shown to comigrate in the polysomal fractions of sucrose gradients, whereas initiation 28 factors usually comigrate with pre-initiation and initiation complexes. Using the CRISPR-Cas9 29 methodology, we deleted one of the two LeishIF4E2 gene copies. The deletion caused severe 30 alterations in the morphology of mutant cells that turned round and equipped with a very short 31 flagellum, but their growth rate and general translation remained unaffected. Proteomic analysis 32 of the LeishIF4E2(+/-) mutant cells compared to wild type controls showed that the number of 33 proteins that were upregulated exceeded the number of downregulated proteins, possibly 34 indicating that a repressor function was eliminated. The upregulated proteins were related mainly 35 to general metabolic processes, DNA repair and replication, signaling, and cellular motor 36 activity. The downregulated proteins included several groups, including cytoskeletal and 37 ribosomal proteins. Despite the fact that only one of the two LeishIF4E2 alleles was deleted, the 38 mutant cells were impaired in their ability to infect cultured macrophages. LeishIF4E2 does not 39 behave like a general translation factor and its function remains elusive. Although it could have a 40 repressive function, we cannot exclude the possibility that it is responsible for translation of a 41 specific set of transcripts. Overall, our results are in line with the possibility that the different 42 LeishIF4Es are assigned unique functions. 43 44 Author summary 45 Leishmania parasites cause a broad spectrum of diseases that lead to different 46 pathological symptoms. During their life cycle, the parasites shuffle between sand-fly 47 vectors and mammalian hosts, while adapting to changing environments via a stage 48 specific program of gene expression that assists the survival of Leishmania under the 49 changing conditions. Translation initiation plays a key role in control of gene expression, 50 in Leishmania this is exemplified by the presence of multiple cap-binding complexes that 51 interact with mRNAs. The parasites encode multiple paralogs of the cap-binding 52 translation initiation factor eIF4E, and of its corresponding binding partner eIF4G, 53 forming complexes with different potential functions. Using the CRISPR-Cas9 54 methodology, we generated a heterozygous mutant of the least studied cap-binding 55 pa...

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Section: Legends To Supplemental Materialsmentioning

confidence: 99%

Distinct features of theLeishmaniacap-binding protein LeishIF4E2 revealed by CRISPR-Cas9 mediated heterozygous deletion

Baron

Tupperwar

Davidov

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…Samples from the same strain were precisely clustered based on all proteins and on the differential ones. Curiously, SOD, HSP70, and TXNPx were increased in the soluble extract of the less virulent LV79 strain . A similar study compared proteomes of L. infantum chagasi promastigotes from strains with different virulence.…”

Section: Potential Applications Of Proteomics In Leishmaniasismentioning

confidence: 95%

“…The search for differentially abundant proteins between strains with different virulence is usually employed to identify virulence factors. Our group has recently compared proteomes of lesion derived amastigotes from two L. amazonensis strains with distinct infectivity in vivo and in vitro . Samples from the same strain were precisely clustered based on all proteins and on the differential ones.…”

Section: Potential Applications Of Proteomics In Leishmaniasismentioning

confidence: 99%

“…Our group has recently compared proteomes of lesion derived amastigotes from two L. amazonensis strains with distinct infectivity in vivo and in vitro. [173] Samples from the same strain were precisely clustered based on all proteins and on the differential ones. Curiously, SOD, HSP70, and TXNPx were increased in the soluble extract of the less virulent LV79 strain.…”

Section: Parasite Virulencementioning

confidence: 99%

“…Curiously, SOD, HSP70, and TXNPx were increased in the soluble extract of the less virulent LV79 strain. [173] A similar study compared proteomes of L. infantum chagasi promastigotes from strains with different virulence. The more virulent strain had higher levels of kinetoplastid membrane protein and metallopeptidase.…”

Section: Parasite Virulencementioning

confidence: 99%

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Proteomics and Leishmaniasis: Potential Clinical Applications

Capelli-Peixoto

Mule

Tano

et al. 2019

Proteomics Clinical Apps

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Leishmaniases are diseases caused by protozoan parasites of the genus Leishmania. They are endemic in 98 countries, affect around 12 million people worldwide and may present several distinct clinical forms. Unfortunately, there are only a few drugs available for treatment of leishmaniasis, which are toxic and not always effective. Different parasite species and different clinical forms require optimization of the treatment or more specific therapies, which are not available. The emergence of resistance is also a matter of concern. Besides, diagnosis can sometimes be complicated due to atypical manifestations and associations with other pathologies. In this review, proteomic data are presented and discussed in terms of their application in important issues in leishmaniasis such as parasite resistance to chemotherapy, diagnosis of active disease in patients and dogs, markers for different clinical forms, identification of virulence factors, and their potential use in vaccination. It is shown that proteomics has contributed to the discovery of potential biomarkers for prognosis, diagnosis, therapeutics, monitoring of disease progression, treatment follow‐up and identification of vaccine candidates for specific diseases. However, the authors believe its capabilities have not yet been fully explored for routine clinical analysis for several reasons, which will be presented in this review.

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Differentially modulated proteins associated with Leishmaniasis—a systematic review of in-vivo and in-vitro studies

2020

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High-throughput proteomic technologies are widely used for understanding the disease mechanism, drug-resistant mechanism, and to identify drug targets and markers for diagnostics. Studies with proteomics applications, relating to Leishmaniasis, are being constantly reported in the literature. However, from such studies, a readily accessible knowledge of differentially modulated proteins associated with Leishmaniasis is lacking. Hence, we performed a systematic review concerning differentially modulated proteins (DMP) in Leishmania as well as host infected with Leishmania from the published articles between the years 2000 and 2019. This review is classified into five different sections, namely, DMP in the host after Leishmania infection, DMP between different strains of Leishmania , DMP in drug-resistant Leishmania , DMP in Leishmania under stress, and DMP in different life stages of Leishmania. A lot of consensuses could be observed among the DMP in drug-resistant and stressed Leishmania . In addition to the review, a database was constructed with the data collected in this study (protein accession ID, protein name, gene name, host organism, experimental conditions, fold change, and regulatory data). A total of 2635 records are available in the database. We believe this review and the database will help the researcher in understanding the disease better and provide information for the targeted proteomics study related to Leishmaniasis. Database availability: http://ldepdb.biomedinformri.com/ . Electronic supplementary material The online version of this article (10.1007/s11033-020-05936-z) contains supplementary material, which is available to authorized users.

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Quantitative proteomic analysis of amastigotes from Leishmania (L.) amazonensis LV79 and PH8 strains reveals molecular traits associated with the virulence phenotype

Cited by 23 publications

References 55 publications

Distinct features of theLeishmaniacap-binding protein LeishIF4E2 revealed by CRISPR-Cas9 mediated heterozygous deletion

Distinct features of theLeishmaniacap-binding protein LeishIF4E2 revealed by CRISPR-Cas9 mediated heterozygous deletion

Proteomics and Leishmaniasis: Potential Clinical Applications

Differentially modulated proteins associated with Leishmaniasis—a systematic review of in-vivo and in-vitro studies

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