Using Proteomics to Understand How Leishmania Parasites Survive inside the Host and Establish Infection

Veras, Patrícia Sampaio Tavares; Menezes, Juliana Perrone Bezerra de

doi:10.3390/ijms17081270

Cited by 31 publications

(23 citation statements)

References 77 publications

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“…This is because post-transcriptional regulations (via microRNAs and other non-coding small RNAs) appear to substantially change the genetic information processing from messenger RNA to protein [45,46]. Information captured at protein expression level might be more reliable to reflect the biological differences between resistant and susceptible strains of the parasite [47]. Indeed, proteomic studies of Leishmania spp.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, proteomic studies of Leishmania spp. have contributed significantly to understanding the surval, infection and drug resistance of this and related parasite [30,47]. For instance, by comparing the protein abundance between stains of different phenotypes, molecules such as alpha-tubulin, cyclophilin-A, heat-shock proteins, pteridine reductase, superoxide dismutase and tryparedoxin peroxidase have been linked to the resistance and/or virulence of Leishmania species [48,49].…”

Section: Discussionmentioning

confidence: 99%

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Integrative genomic, proteomic and phenotypic studies of Leishmania donovani strains revealed genetic features associated with virulence and antimony-resistance

Zheng

Chen

et al. 2020

Parasites Vectors

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Background Leishmaniasis is a neglected tropical disease affecting millions of people worldwide. Emerging drug resistance of Leishmania species poses threaten to the effective control and elimination programme of this neglected tropical disease. Methods In this work, we conducted drug-resistance testing, whole genome resequencing and proteome profiling for a recently reported clinical isolate with supposed drug resistance (HCZ), and two reference sensitive strains (DD8 and 9044) of Leishmania donovani, to explore molecular mechanisms underlying drug resistance in this parasite. Results With reference to DD8 and 9044 strains, HCZ isolate showed higher-level virulence and clear resistance to antimonials in promastigote culture, infected macrophages and animal experiment. Pairwise genomic comparisons revealed genetic variations (86 copy number variations, 271 frameshift mutations in protein-coding genes and two site mutations in non-coding genes) in HCZ isolate that were absent from the reference sensitive strains. Proteomic analysis indicated different protein expression between HCZ isolate and reference strains, including 69 exclusively detected proteins and 82 consistently down-/upregulated molecules in the HCZ isolate. Integrative analysis showed linkage of 12 genomic variations (gene duplication, insertion and deletion) and their protein expression changes in HCZ isolate, which might be associated with pathogenic and antimony-resistant phenotype. Functional annotation analyses further indicated that molecules involved in nucleotide-binding, fatty acid metabolism, oxidation-reduction and transport might play a role in host-parasite interaction and drug-resistance. Conclusions This comprehensive integrative work provided novel insights into the genetic basis underlying virulence and resistance, suggesting new aspects to be investigated for a better intervention against L. donovani and associated diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Integrative genomic, proteomic and phenotypic studies of Leishmania donovani strains revealed genetic features associated with virulence and antimony-resistance

Zheng

Chen

et al. 2020

Parasites Vectors

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“…These approaches have been lauded due to their greater effectiveness than focusing exclusively on individual molecules, which rarely lend insight into disease pathogenesis. RNA-seq and proteomics, both large-scale techniques designed to characterize genes or proteins in a given cell line, tissue, or organism, offer the advantage of a more global and integrated view of the myriad biological processes that occur within cells (Wang et al, 2009 ; Veras and Bezerra De Menezes, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

In Search of Biomarkers for Pathogenesis and Control of Leishmaniasis by Global Analyses of Leishmania-Infected Macrophages

Veras¹,

Ramos²,

Menezes

2018

Front. Cell. Infect. Microbiol.

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Leishmaniasis is a vector-borne, neglected tropical disease with a worldwide distribution that can present in a variety of clinical forms, depending on the parasite species and host genetic background. The pathogenesis of this disease remains far from being elucidated because the involvement of a complex immune response orchestrated by host cells significantly affects the clinical outcome. Among these cells, macrophages are the main host cells, produce cytokines and chemokines, thereby triggering events that contribute to the mediation of the host immune response and, subsequently, to the establishment of infection or, alternatively, disease control. There has been relatively limited commercial interest in developing new pharmaceutical compounds to treat leishmaniasis. Moreover, advances in the understanding of the underlying biology of Leishmania spp. have not translated into the development of effective new chemotherapeutic compounds. As a result, biomarkers as surrogate disease endpoints present several potential advantages to be used in the identification of targets capable of facilitating therapeutic interventions considered to ameliorate disease outcome. More recently, large-scale genomic and proteomic analyses have allowed the identification and characterization of the pathways involved in the infection process in both parasites and the host, and these analyses have been shown to be more effective than studying individual molecules to elucidate disease pathogenesis. RNA-seq and proteomics are large-scale approaches that characterize genes or proteins in a given cell line, tissue, or organism to provide a global and more integrated view of the myriad biological processes that occur within a cell than focusing on an individual gene or protein. Bioinformatics provides us with the means to computationally analyze and integrate the large volumes of data generated by high-throughput sequencing approaches. The integration of genomic expression and proteomic data offers a rich multi-dimensional analysis, despite the inherent technical and statistical challenges. We propose that these types of global analyses facilitate the identification, among a large number of genes and proteins, those that hold potential as biomarkers. The present review focuses on large-scale studies that have identified and evaluated relevant biomarkers in macrophages in response to Leishmania infection.

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“…These promastigotes are then phagocytosed by cells at the site of the bite. Once inside the host cells, metacyclic promastigotes transform into amastigotes, which can survive and replicate inside phagolysosomes (Veras & Bezerra de Menezes, 2016). The first‐line drugs for leishmaniasis are pentavalent antimonials.…”

Section: Resveratrol and Diseasesmentioning

confidence: 99%

Resveratrol: A miraculous natural compound for diseases treatment

Koushki

Amiri-Dashatan

Ahmadi

et al. 2018

Food Science & Nutrition

210

109

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Resveratrol (3, 5, 4′‐trihydroxystilbene) is a nonflavonoid polyphenol that naturally occurs as phytoalexin. It is produced by plant sources such as grapes, apples, blueberries, plums, and peanut. This compound has critical roles in human health and is well known for its diverse biological activities such as antioxidant and anti‐inflammatory properties. Nowadays, due to rising incidence of different diseases such as cancer and diabetes, efforts to find novel and effective disease‐protective agents have led to the identification of plant‐derived compounds such as resveratrol. Furthermore, several in vitro and in vivo studies have revealed the effectiveness of resveratrol in various diseases such as diabetes mellitus, cardiovascular disease, metabolic syndrome, obesity, inflammatory, neurodegenerative, and age‐related diseases. This review presents an overview of currently available studies on preventive properties and essential molecular mechanisms involved in various diseases.

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Using Proteomics to Understand How Leishmania Parasites Survive inside the Host and Establish Infection

Cited by 31 publications

References 77 publications

Integrative genomic, proteomic and phenotypic studies of Leishmania donovani strains revealed genetic features associated with virulence and antimony-resistance

Integrative genomic, proteomic and phenotypic studies of Leishmania donovani strains revealed genetic features associated with virulence and antimony-resistance

In Search of Biomarkers for Pathogenesis and Control of Leishmaniasis by Global Analyses of Leishmania-Infected Macrophages

Resveratrol: A miraculous natural compound for diseases treatment

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