The role of dogs as reservoirs of Leishmania parasites, with emphasis on Leishmania (Leishmania) infantum and Leishmania (Viannia) braziliensis

ABSTRACTLeishmaniasis is a widespread neglected tropical disease caused by parasites of theLeishmaniagenus. These parasites express the enzyme 3′-nucleotidase/nuclease (3′NT/NU), which has been described to be involved in parasite nutrition and infection. Bacteria that express nucleases escape the toxic effects of neutrophil extracellular traps (NETs). Hence, we investigated the role of 3′NT/NU inLeishmaniasurvival of NET-mediated killing. Promastigotes ofLeishmania infantumwere cultured in high-phosphate (HP) or low-phosphate (LP) medium to modulate nuclease activity. We compared the survival of the two different groups ofLeishmaniaduring interaction with human neutrophils, assessing the role of neutrophil extracellular traps. As previously reported, we detected higher nuclease activity in parasites cultured in LP medium. Both LP and HP promastigotes were capable of inducing the release of neutrophil extracellular traps from human neutrophils in a dose- and time-dependent manner. LP parasites had 2.4 times more survival than HP promastigotes. NET disruption was prevented by the treatment of the parasites with ammonium tetrathiomolybdate (TTM), a 3′NT/NU inhibitor. Inhibition of 3′NT/NU by 3′-AMP, 5′-GMP, or TTM decreased promastigote survival upon interaction with neutrophils. Our results show thatLeishmania infantuminduces NET release and that promastigotes can escape NET-mediated killing by 3′-nucleotidase/nuclease activity, thus ascribing a new function to this enzyme.

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The role of the C-terminus and Kpn loop in the quaternary structure stability of nucleoside diphosphate kinase from Leishmania parasites

Journal of Structural Biology ◽

10.1016/j.jsb.2015.09.009 ◽

2015 ◽

Vol 192 (3) ◽

pp. 336-341 ◽

Cited By ~ 4

Author(s):

Plínio Salmazo Vieira ◽

Priscila Oliveira de Giuseppe ◽

Arthur Henrique Cavalcante de Oliveira ◽

Mario Tyago Murakami

Keyword(s):

Quaternary Structure ◽

Nucleoside Diphosphate Kinase ◽

Structure Stability ◽

C Terminus ◽

Leishmania Parasites

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Sexual and vertical transmission of visceral leishmaniasis

The Journal of Infection in Developing Countries ◽

10.3855/jidc.4108 ◽

2014 ◽

Vol 8 (04) ◽

pp. 403-407 ◽

Cited By ~ 17

Author(s):

Andreia P Turchetti ◽

Tayse D Souza ◽

Tatiane A Paixão ◽

Renato L. Santos

Keyword(s):

Visceral Leishmaniasis ◽

Vertical Transmission ◽

Leishmania Infantum ◽

Vertebrate Host ◽

Domestic Dog ◽

Sand Flies ◽

Phlebotomine Sand Flies

Visceral leishmaniasis (VL) is an important zoonosis caused by Leishmania infantum, which has in the domestic dog its principal vertebrate host. VL is usually transmitted by phlebotomine sand flies, however atypical routes of transmission have been described. In this review we discuss the the role of sexual and vertical transmissions, and their role in the maintenance of VL in canine populations.

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In vitro and in vivo resistance of Leishmania infantum to meglumine antimoniate: a study of 37 strains collected from patients with visceral leishmaniasis.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.41.4.827 ◽

1997 ◽

Vol 41 (4) ◽

pp. 827-830 ◽

Cited By ~ 140

Author(s):

F Faraut-Gambarelli ◽

R Piarroux ◽

M Deniau ◽

B Giusiano ◽

P Marty ◽

...

Keyword(s):

Visceral Leishmaniasis ◽

Leishmania Infantum ◽

Strongly Correlated ◽

Duration Of Treatment ◽

In Vitro Sensitivity ◽

Sensitivity Tests ◽

Leishmania Parasites ◽

Immunocompetent Patients

Primary and secondary unresponsiveness to meglumine has long been described in human visceral leishmaniasis. However, no studies have been performed to elucidate if these therapeutic failures were due to strain variability in meglumine sensitivity or were related to host factors. We have studied the in vitro sensitivity of 37 strains of Leishmania infantum isolated from 23 patients (11 human immunodeficiency virus-infected and 12 immunocompetent patients) with visceral leishmaniasis. Sensitivity tests were performed by infecting murine macrophages with Leishmania parasites and culturing them in medium containing different concentrations of meglumine. For each test we calculated a 50% effective dose (ED50) corresponding to the meglumine concentration at which 50% of the Leishmania parasites survived. In vitro results were strongly correlated to immediate clinical outcome. All strains requiring an ED50 of >70 microg/ml were related to therapeutic failures, whereas all strains requiring an ED50 of <40 microg/ml corresponded to an initial efficiency of meglumine. Among those patients who were initially improved, relapses occurred in all immunocompromised patients and in most immunocompetent patients who had a short duration of treatment (15 days). Finally, we found that in vitro sensitivity of strains decreased progressively in relapsing patients treated with meglumine. Consequently, the physician may be encouraged to alternate meglumine with other treatments such as amphotericin B or pentamidine, especially in the case of relapsing patients.

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Role of Reactive Oxygen Species in Infection by the Intracellular Leishmania Parasites

Oxidative Stress in Microbial Diseases ◽

10.1007/978-981-13-8763-0_16 ◽

2019 ◽

pp. 297-311

Author(s):

Moumita Basu ◽

Pijush K. Das

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Oxygen Species ◽

Leishmania Parasites

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Chitin binding protein as a possible RNA binding protein in Leishmania parasites

Pathogens and Disease ◽

10.1093/femspd/ftaa007 ◽

2020 ◽

Vol 78 (1) ◽

Author(s):

Sajad Rashidi ◽

Kurosh Kalantar ◽

Celia Fernandez-Rubio ◽

Enayat Anvari ◽

Paul Nguewa ◽

...

Keyword(s):

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Novel Proteins ◽

Transcriptional Gene Regulation ◽

Chitin Binding Protein ◽

Effective Drugs ◽

Genus Leishmania ◽

Leishmania Parasites

ABSTRACT Leishmaniasis includes a broad spectrum of pathological outcomes in humans caused by protozoan parasites from the genus Leishmania. In recent years, proteomic techniques have introduced novel proteins with critical functions in Leishmania parasites. Based on our report of a Chitin binding protein (CBP) in our previous immunoproteomic study, this article suggests that CBP might be an RNA binding protein (RBP) in Leishmania parasites. RBPs, as key regulatory factors, have a role in post-transcriptional gene regulation. The presence of RBPs in Leishmania parasites has not been considered so far; however, this study aims to open a new venue regarding RBPs in Leishmania parasites. Confirming CBP as an RBP in Leishmania parasites, exploring other RBPs and their functions might lead to interesting issues in leishmaniasis. In fact, due to the regulatory role of RBPs in different diseases including cancers and their further classification as therapeutic targets, the emerging evaluation of CBP and RBPs from Leishmania parasites may allow the discovery of novel and effective drugs against leishmaniasis.

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Resistance to Experimental Visceral Leishmaniasis in Mice Infected With Leishmania infantum Requires Batf3

Frontiers in Immunology ◽

10.3389/fimmu.2020.590934 ◽

2020 ◽

Vol 11 ◽

Author(s):

Manuel Soto ◽

Laura Ramírez ◽

José Carlos Solana ◽

Emma C. L. Cook ◽

Elena Hernández-García ◽

...

Keyword(s):

Visceral Leishmaniasis ◽

Leishmania Infantum ◽

Rational Design ◽

Leucine Zipper ◽

Basic Leucine Zipper ◽

Vector Borne ◽

The Impact ◽

Deficient Mice

Unveiling the protective immune response to visceral leishmaniasis is critical for a rational design of vaccines aimed at reducing the impact caused by this fatal, if left untreated, vector-borne disease. In this study we sought to determine the role of the basic leucine zipper transcription factor ATF-like 3 (Batf3) in the evolution of infection with Leishmania infantum, the causative agent of human visceral leishmaniasis in the Mediterranean Basin and Latin America. For that, Batf3-deficient mice in C57BL/6 background were infected with an L. infantum strain expressing the luciferase gene. Bioluminescent imaging, as well as in vitro parasite titration, demonstrated that Batf3-deficient mice were unable to control hepatic parasitosis as opposed to wild-type C57BL/6 mice. The impaired microbicide capacities of L. infantum-infected macrophages from Batf3-deficient mice mainly correlated with a reduction of parasite-specific IFN-γ production. Our results reinforce the implication of Batf3 in the generation of type 1 immunity against infectious diseases.

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First Report of Canine Infection by Leishmania (Viannia) guyanensis in the Brazilian Amazon

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17228488 ◽

2020 ◽

Vol 17 (22) ◽

pp. 8488

Author(s):

Francisco J. A. Santos ◽

Luciana C. S. Nascimento ◽

Wellington B. Silva ◽

Luciana P. Oliveira ◽

Walter S. Santos ◽

...

Keyword(s):

Leishmania Infantum ◽

Blood Collection ◽

Wild Mammals ◽

First Report ◽

Transmission Cycle ◽

First Choice ◽

Human Leishmaniasis ◽

Leishmania Spp ◽

Canine Infection

The American cutaneous (CL) and visceral leishmaniasis (VL) are zooanthroponoses transmitted by sand flies. Brazil records thousands of human leishmaniasis cases annually. Dogs are reservoirs of Leishmania infantum, which causes VL, but their role in the transmission cycle of CL is debatable. Wild mammals are considered reservoirs of the aetiological agents of CL (Leishmania spp.). Objective: To describe the aetiology of leishmaniasis in dogs in an endemic area for CL and VL in the Amazon, Brazil. Methods: Clinical evaluation and blood collection of 40 dogs from the villages Ubim (20) and Socorro (20), city of Tomé-Açu, state of Pará, were carried out. The DNA extracted from the blood was used for PCR with Leishmania-specific primers targeting the hsp70-234 gene sequence. Products were sequenced (ABI3500XL), and the sequences were aligned, edited (BioEdit), and analyzed (Blastn). Results: Of the 34 amplified samples, 21 were sequenced, namely Leishmania infantum (12), L. guyanensis (5), L. braziliensis (3), and Leishmania sp. (01). Conclusion: Given the diversity of circulating pathogens, elucidation of the role of the dog in the Leishmania spp. cycle in Amazonian villages is imperative to the surveillance of CL in the region. We present the first report in Brazil, confirmed by sequencing, of canine infection by L. guyanensis, a species highly resistant to treatment in humans, with the drug of first choice (Glucantime®).

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