Zinc depletion promotes apoptosis-like death in drug-sensitive and antimony-resistance Leishmania donovani

Saini, Shalini; Bharati, Kavita; Shaha, Chandrima; Mukhopadhyay, Chinmay K.

doi:10.1038/s41598-017-10041-6

Cited by 18 publications

(10 citation statements)

References 60 publications

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“…LD (MHOM\IN\1983\AG83) was used for all experiments. Culture and maintenance of the virulent parasites by passaging through Balb/ c mice were performed as described before (Das et al, 2009;Saini, Bharati, Shaha, & Mukhopadhyay, 2017). Freshly transformed promastigotes were maintained in M199 medium supplemented with 10% FBS, 100 units/ml penicillin, 100 μg/ml streptomycin at 22°C.…”

Section: Parasite Culturementioning

confidence: 99%

Leishmania donovaniinhibits ferroportin translation by modulating FBXL5-IRP2 axis for its growth within host macrophages

Das

Sandhya

Vivek

et al. 2018

Cellular Microbiology

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Hepcidin mediated ferroportin (Fpn) degradation in macrophages is a well adopted strategy to limit iron availability towards invading pathogens. Leishmania donovani (LD), a protozoan parasite, resides within macrophage and competes with host for availing iron. Using in vitro and in vivo model of infection, we reveal that LD decreases Fpn abundance in host macrophages by hepcidin independent mechanism. Unaffected level of Fpn-FLAG in LD infected J774 macrophage confirms that Fpn down-regulation is not due its degradation. While increased Fpn mRNA but decreased protein expression in macrophages suggests blocking of Fpn translation by LD infection that is confirmed by S-methionine labelling assay. We further reveal that LD blocks Fpn translation by induced binding of iron regulatory proteins (IRPs) to the iron responsive element present in its 5'UTR. Supershift analysis provides evidence of involvement of IRP2 particularly during in vivo infection. Accordingly, a significant increase in IRP2 protein expression with simultaneous decrease in its stability regulator F-box and leucine-rich repeat Protein 5 (FBXL5) is detected in splenocytes of LD-infected mice. Increased intracellular growth due to compromised expressions of Fpn and FBXL5 by specific siRNAs reveals that LD uses a novel strategy of manipulating IRP2-FBXL5 axis to inhibit host Fpn expression.

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Section: Parasite Culturementioning

confidence: 99%

Leishmania donovaniinhibits ferroportin translation by modulating FBXL5-IRP2 axis for its growth within host macrophages

Das

Sandhya

Vivek

et al. 2018

Cellular Microbiology

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“…Additionally, the ontology enrichment analysis revealed that most genes with CNVs were involved in cellular ion zinc homeostasis in many clinical isolates; some of these genes were previously identified in L. infantum [63], as reported by a previous study, wherein the authors have described the need of these genes in the parasite to maintain the intracellular concentrations of zinc and avoid the toxic effects of this metal. Considering the aforementioned findings, we believe that L. panamensis, similar to other Leishmania species, needs to maintain intracellular zinc homeostasis because of the importance of this metal as a cofactor of several hundred proteins involved in replication, infectivity, and virulence [64,65]. Another group of genes with CNVs observed in some genomes was associated with glycerol transport.…”

Section: Discussionmentioning

confidence: 95%

Intraspecific Genomic Divergence and Minor Structural Variations in Leishmania (Viannia) panamensis

Patiño

Muñoz

Muskus

et al. 2020

Genes

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Leishmania (Viannia) panamensis is one of the most important Leishmania species associated with cutaneous leishmaniasis (CL) in Latin America. Despite its wide geographic distribution and pathogenic potential in humans and animals, the genomic variability of this species is low compared with other Leishmania species circulating in the same geographical area. No studies have reported a detailed analysis of the whole genome of L. panamensis from clinical isolates using DNA high-throughput sequencing to clarify its intraspecific genomic variability or plausible divergence. Therefore, this study aimed to evaluate the intraspecific genomic variability of L. panamensis from Colombia and Panama. A total of 22 genomes were analyzed, 19 from Colombian patients with CL and three genomes from Panama obtained from public databases. The phylogenomic analysis revealed the potential existence of three well-supported clades as evidence of intraspecific divergence. Additionally, the whole-genome analysis showed low structural variations in terms of ploidy, copy number variations, and single-nucleotide polymorphisms (SNPs). SNPs shared among all clades were identified, revealing their importance in different biological processes of L. panamensis. The findings not only expand our knowledge of intraspecific genomic variability of one of the most important Leishmania species in South America but also highlights the possible existence of different clades/lineages/subpopulations across a geographic scale.

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“…TPEN has been used as a zinc chelator in several studies [15][16][17]. Therefore, we tested the effect of zinc on biofilm formation by T. asahii.…”

Section: Resultsmentioning

confidence: 99%

N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine, a zinc chelator, inhibits biofilm and hyphal formation in Trichosporon asahii

et al. 2020

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Objective: Trichosporon asahii is the major causative fungus of disseminated or deep-seated trichosporonosis and forms a biofilm on medical devices. Biofilm formation leads to antifungal drug resistance, so biofilm-related infections are relatively difficult to treat and infected devices often require surgical removal. Therefore, prevention of biofilm formation is important in clinical settings. In this study, to identify metal cations that affect biofilm formation, we evaluated the effects of cation chelators on biofilm formation in T. asahii. Results: We evaluated the effect of cation chelators on biofilm formation, since microorganisms must assimilate essential nutrients from their hosts to form and maintain biofilms. The inhibition by N,N,N′,N′-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN) was greater than those by other cation chelators, such as deferoxamine, triethylenetetramine, and ethylenediaminetetraacetic acid. The inhibitory effect of TPEN was suppressed by the addition of zinc. TPEN also inhibited T. asahii hyphal formation, which is related to biofilm formation, and the inhibition was suppressed by the addition of zinc. These results suggest that zinc is essential for biofilm formation and hyphal formation. Thus, zinc chelators have the potential to be developed into a new treatment for biofilm-related infection caused by T. asahii.

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Zinc depletion promotes apoptosis-like death in drug-sensitive and antimony-resistance Leishmania donovani

Cited by 18 publications

References 60 publications

Leishmania donovaniinhibits ferroportin translation by modulating FBXL5-IRP2 axis for its growth within host macrophages

Leishmania donovaniinhibits ferroportin translation by modulating FBXL5-IRP2 axis for its growth within host macrophages

Intraspecific Genomic Divergence and Minor Structural Variations in Leishmania (Viannia) panamensis

N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine, a zinc chelator, inhibits biofilm and hyphal formation in Trichosporon asahii

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