A2 and Other Visceralizing Proteins of Leishmania: Role in Pathogenesis and Application for Vaccine Development

Fernandes, Ana Paula; Canavaci, Adriana Monte Cassiano; McCall, Laura-Isobel; Matlashewski, Greg

doi:10.1007/978-94-007-7305-9_3

Cited by 12 publications

(8 citation statements)

References 115 publications

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“…The A2 gene locus, which has been the focus of several studies exploring the parasite’s invasive characteristics during infection [ 14 , 51 , 52 ], was not seen to be differentially distributed among CL-SL and VL-SL groups in our study. This finding suggests that intra species variations resulting in different tropisms are likely to be influenced by many genes and their cumulative effects, as compared to phenotypic differences being determined by variations in a single gene locus or region.…”

Section: Discussioncontrasting

confidence: 46%

Genomic insights into virulence mechanisms of Leishmania donovani: evidence from an atypical strain

et al. 2018

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BackgroundLeishmaniasis is a neglected tropical disease with diverse clinical phenotypes, determined by parasite, host and vector interactions. Despite the advances in molecular biology and the availability of more Leishmania genome references in recent years, the association between parasite species and distinct clinical phenotypes remains poorly understood. We present a genomic comparison of an atypical variant of Leishmania donovani from a South Asian focus, where it mostly causes cutaneous form of leishmaniasis.ResultsClinical isolates from six cutaneous leishmaniasis patients (CL-SL); 2 of whom were poor responders to antimony (CL-PR), and two visceral leishmaniasis patients (VL-SL) were sequenced on an Illumina MiSeq platform. Chromosome aneuploidy was observed in both groups but was more frequent in CL-SL. 248 genes differed by 2 fold or more in copy number among the two groups. Genes involved in amino acid use (LdBPK_271940) and energy metabolism (LdBPK_271950), predominated the VL-SL group with the same distribution pattern reflected in gene tandem arrays. Genes encoding amastins were present in higher copy numbers in VL-SL and CL-PR as well as being among predicted pseudogenes in CL-SL. Both chromosome and SNP profiles showed CL-SL and VL-SL to form two distinct groups. While expected heterozygosity was much higher in VL-SL, SNP allele frequency patterns did not suggest potential recent recombination breakpoints. The SNP/indel profile obtained using the more recently generated PacBio sequence did not vary markedly from that based on the standard LdBPK282A1 reference. Several genes previously associated with resistance to antimonials were observed in higher copy numbers in the analysis of CL-PR. H-locus amplification was seen in one cutaneous isolate which however did not belong to the CL-PR group.ConclusionsThe data presented suggests that intra species variations at chromosome and gene level are more likely to influence differences in tropism as well as response to treatment, and contributes to greater understanding of parasite molecular mechanisms underpinning these differences. These findings should be substantiated with a larger sample number and expression/functional studies.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-5271-z) contains supplementary material, which is available to authorized users.

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Section: Discussioncontrasting

confidence: 46%

Genomic insights into virulence mechanisms of Leishmania donovani: evidence from an atypical strain

et al. 2018

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“…However, interestingly, A2 gene is mostly expressed in parasites causing VL but not CL. Moreover, antibody response against A2 gene was reported in human VL patients and infected dog sera but not in CL-infected individuals [ 126 ], indicating a prospective role of A2 in viscerelization of Leishmania parasites in mammalian organs [ 127 ]. A2 gene encodes for a total seven isotypes of proteins with molecular weights ranging from 45 to 100 kDa.…”

Section: Heat Shock Protein (Hsps)mentioning

confidence: 99%

The pathogenicity and virulence of Leishmania - interplay of virulence factors with host defenses

et al. 2022

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Leishmaniasis is a group of disease caused by the intracellular protozoan parasite of the genus Leishmania . Infection by different species of Leishmania results in various host immune responses, which usually lead to parasite clearance and may also contribute to pathogenesis and, hence, increasing the complexity of the disease. Interestingly, the parasite tends to reside within the unfriendly environment of the macrophages and has evolved various survival strategies to evade or modulate host immune defense. This can be attributed to the array of virulence factors of the vicious parasite, which target important host functioning and machineries. This review encompasses a holistic overview of leishmanial virulence factors, their role in assisting parasite-mediated evasion of host defense weaponries, and modulating epigenetic landscapes of host immune regulatory genes. Furthermore, the review also discusses the diagnostic potential of various leishmanial virulence factors and the advent of immunomodulators as futuristic antileishmanial drug therapy.

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“…Another signature of this subgenus is high expression of molecules such as glycoprotein (GP) GP63 and GP46, known surface components that act on the tropism of CL, development inside the vector, and neutralization of the host macrophage defense system [ 19 – 23 ]. The subgenus Leishmania ( Leishmania ) has targets associated with visceral leishmaniasis (VL), such as the genes encoding proteins A2 and 6-phosphogluconate dehydrogenase (6PGDH), besides differential expression of genes such as the catalytic subunit of DNA polymerase A (POLA), heat-shock protein 20 (HSP20), or N-acetylglucosamine-phosphotransferase (NAGT) [ 24 – 26 ].…”

Section: Introductionmentioning

confidence: 99%

Comparative analysis of the transcriptional responses of five Leishmania species to trivalent antimony

et al. 2021

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Background Leishmaniasis is a neglected tropical disease caused by several species of Leishmania. The resistance phenotype of these parasites depends on the characteristics of each species, which contributes to increased therapeutic failures. Understanding the mechanism used by the parasite to survive under treatment pressure in order to identify potential common and specific therapeutic targets is essential for the control of leishmaniasis. The aim of this study was to investigate the expression profiles and potential shared and specific resistance markers of the main Leishmania species of medical importance [subgenus L. (Leishmania): L. donovani, L. infantum and L. amazonensis; subgenus L. (Viannia): L. panamensis and L. braziliensis)] resistant and sensitive to trivalent stibogluconate (SbIII). Methods We conducted comparative analysis of the transcriptomic profiles (only coding sequences) of lines with experimentally induced resistance to SbIII from biological replicates of five Leishmania species available in the databases of four articles based on ortholog attribution. Simultaneously, we carried out functional analysis of ontology and reconstruction of metabolic pathways of the resulting differentially expressed genes (DEGs). Results Resistant lines for each species had differential responses in metabolic processes, compound binding, and membrane components concerning their sensitive counterpart. One hundred and thirty-nine metabolic pathways were found, with the three main pathways comprising cysteine and methionine metabolism, glycolysis, and the ribosome. Differentially expressed orthologous genes assigned to species-specific responses predominated, with 899 self-genes. No differentially expressed genes were found in common among the five species. Two common upregulated orthologous genes were found among four species (L. donovani, L. braziliensis, L. amazonensis, and L. panamensis) related to an RNA-binding protein and the NAD(P)H cytochrome-B5-oxidoreductase complex, associated with transcriptional control and de novo synthesis of linoleic acid, critical mechanisms in resistance to antimonials. Conclusion Herein, we identified potential species-specific genes related to resistance to SbIII. Therefore, we suggest that future studies consider a treatment scheme that is species-specific. Despite the limitations of our study, this is the first approach toward unraveling the pan-genus genetic mechanisms of resistance in leishmaniasis. Graphical Abstract

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A2 and Other Visceralizing Proteins of Leishmania: Role in Pathogenesis and Application for Vaccine Development

Cited by 12 publications

References 115 publications

Genomic insights into virulence mechanisms of Leishmania donovani: evidence from an atypical strain

Genomic insights into virulence mechanisms of Leishmania donovani: evidence from an atypical strain

The pathogenicity and virulence of Leishmania - interplay of virulence factors with host defenses

Comparative analysis of the transcriptional responses of five Leishmania species to trivalent antimony

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