Differences in the Antigenic Profile and Infectivity of Murine Macrophages of Leishmania (Viannia) Parasites

Matta, Nubia E.; Cysne-Finkelstein, Léa; Machado, Gerzia Maria C.; Da‐Cruz, Alda Maria; Leon, Leonor L.

doi:10.1645/ge-2241.1

Cited by 6 publications

(2 citation statements)

References 35 publications

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“…This is important because infections by the Viannia are spread by many hosts and all sources of infections need to be addressed. Immunological screening of anti- Leishmania antibodies could be enhanced by genetic testing to identify infections from non-endemic or rarer sources like L. naiffi , which has longer parasite survival rates in macrophages in vitro [ 83 ].…”

Section: Discussionmentioning

confidence: 99%

Leishmania naiffiandLeishmania guyanensisreference genomes highlight genome structure and gene evolution in theVianniasubgenus

et al. 2018

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The unicellular protozoan parasite Leishmania causes the neglected tropical disease leishmaniasis, affecting 12 million people in 98 countries. In South America, where the Viannia subgenus predominates, so far only L. (Viannia) braziliensis and L. (V.) panamensis have been sequenced, assembled and annotated as reference genomes. Addressing this deficit in molecular information can inform species typing, epidemiological monitoring and clinical treatment. Here, L. (V.) naiffi and L. (V.) guyanensis genomic DNA was sequenced to assemble these two genomes as draft references from short sequence reads. The methods used were tested using short sequence reads for L. braziliensis M2904 against its published reference as a comparison. This assembly and annotation pipeline identified 70 additional genes not annotated on the original M2904 reference. Phylogenetic and evolutionary comparisons of L. guyanensis and L. naiffi with 10 other Viannia genomes revealed four traits common to all Viannia: aneuploidy, 22 orthologous groups of genes absent in other Leishmania subgenera, elevated TATE transposon copies and a high NADH-dependent fumarate reductase gene copy number. Within the Viannia, there were limited structural changes in genome architecture specific to individual species: a 45 Kb amplification on chromosome 34 was present in all bar L. lainsoni, L. naiffi had a higher copy number of the virulence factor leishmanolysin, and laboratory isolate L. shawi M8408 had a possible minichromosome derived from the 3’ end of chromosome 34. This combination of genome assembly, phylogenetics and comparative analysis across an extended panel of diverse Viannia has uncovered new insights into the origin and evolution of this subgenus and can help improve diagnostics for leishmaniasis surveillance.

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Section: Discussionmentioning

confidence: 99%

Leishmania naiffiandLeishmania guyanensisreference genomes highlight genome structure and gene evolution in theVianniasubgenus

et al. 2018

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“…braziliensis killing , as observed with L. (V). guyanensis and L. (L.) major [36] – [38] . In CL patients, an exacerbated inflammatory immune response is associated with the development of mucocutaneous leishmaniasis (rev.…”

Section: Discussionmentioning

confidence: 99%

Chemotherapeutic Potential of 17-AAG against Cutaneous Leishmaniasis Caused by Leishmania (Viannia) braziliensis

et al. 2014

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BackgroundLeishmaniasis remains a worldwide public health problem. The limited therapeutic options, drug toxicity and reports of resistance, reinforce the need for the development of new treatment options. Previously, we showed that 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), a Heat Shock Protein 90 (HSP90)-specific inhibitor, reduces L. (L.) amazonensis infection in vitro. Herein, we expand the current knowledge on the leishmanicidal activity of 17-AAG against cutaneous leishmaniasis, employing an experimental model of infection with L. (V.) braziliensis.Methodology/Principal findingsExposure of axenic L. (V.) braziliensis promastigotes to 17-AAG resulted in direct dose-dependent parasite killing. These results were extended to L. (V.) braziliensis-infected macrophages, an effect that was dissociated from the production of nitric oxide (NO), superoxide (O−2) or inflammatory mediators such as TNF-α, IL-6 and MCP-1. The leishmanicidal effect was then demonstrated in vivo, employing BALB/c mice infected with L. braziliensis. In this model, 17-AAG treatment resulted in smaller skin lesions and parasite counts were also significantly reduced. Lastly, 17-AAG showed a similar effect to amphotericin B regarding the ability to reduce parasite viability.Conclusion/Significance17-AAG effectively inhibited the growth of L. braziliensis, both in vitro and in vivo. Given the chronicity of L. (V.) braziliensis infection and its association with mucocutaneous leishmaniasis, 17-AAG can be envisaged as a new chemotherapeutic alternative for cutaneous Leishmaniasis.

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Evidence of Subpopulations with Distinct Biological Features Within a Leishmania (Viannia) braziliensis Strain

Cysne-Finkelstein

Silva-Almeida

Pereira

et al. 2018

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Differences in the Antigenic Profile and Infectivity of Murine Macrophages of Leishmania (Viannia) Parasites

Cited by 6 publications

References 35 publications

Leishmania naiffiandLeishmania guyanensisreference genomes highlight genome structure and gene evolution in theVianniasubgenus

Leishmania naiffiandLeishmania guyanensisreference genomes highlight genome structure and gene evolution in theVianniasubgenus

Chemotherapeutic Potential of 17-AAG against Cutaneous Leishmaniasis Caused by Leishmania (Viannia) braziliensis

Evidence of Subpopulations with Distinct Biological Features Within a Leishmania (Viannia) braziliensis Strain

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