Christopher Fernandez-Prada

Christopher Fernandez-Prada
Université de Montréal | UdeM · Department of Pathology and Microbiology

DVM MSc PhD

About

61
Publications
17,532
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Citations
Introduction
Our research team is focused on the discovery and characterization of novel drug-resistance determinants, as well as biomarkers in sensitive and drug-resistant parasites, with a special focus on the study of exosomes and other extracellular vesicles through the implementation of a variety of omics sciences. Moreover, we have established a novel high-throughput platform for the integrated study of veterinary and zoonotic parasitic diseases, ranging from in vitro assays to complex in vivo models.
Additional affiliations
March 2019 - present
McGill University
Position
  • Professor (Associate)
September 2016 - present
Université de Montréal
Position
  • Professor (Assistant)
August 2016 - present
Université de Montréal
Position
  • Professor (Assistant)
Education
June 2013 - August 2016
Laval University
Field of study
  • Infectiology
September 2010 - May 2013
Universidad de León
Field of study
  • Biomedical Sciences, Molecular Parasitology
September 2008 - September 2010
Universidad de León
Field of study
  • Biomedical Sciences

Publications

Publications (61)
Article
Full-text available
Control of both human and canine leishmaniasis is based on a very short list of chemotherapeutic agents, headed by antimonial derivatives (Sb). The utility of these molecules is severely threatened by high rates of drug resistance. The ABC transporter MRPA is one of the few key Sb resistance proteins described to date, whose role in detoxification...
Article
Full-text available
Leishmaniasis is the 9th largest disease burden among infectious diseases. Control of the disease is based on a short list of chemotherapeutic agents headed by pentavalent antimonials, followed by miltefosine and amphotericin B. These drugs are far from ideal due to host toxicity, elevated cost, limited access, and high rates of drug resistance. Co...
Article
Full-text available
Background The evolution of drug resistance is one of the biggest challenges in leishmaniasis and has prompted the need for new antileishmanial drugs. Repurposing of approved drugs is a faster and very attractive strategy that is gaining supporters worldwide. Different anticancer topoisomerase 1B (TOP1B) inhibitors have shown strong antileishmanial...
Article
Full-text available
Background Asymptomatic Leishmania infection may play an important role in the transmission of the parasite in endemic areas. At present there is no consensus on the definition of asymptomatic Leishmania infection, nor is there a safe and accessible gold standard test for its identification. Methods This paper presents a scoping review to summariz...
Article
In this case series, clinical investigations were pursued during a Synhimantus nasuta infection in a lorikeet (Trichoglossus spp.) flock outbreak situation to better describe and document clinical presentations. In 11 lorikeets suspected to be infected with Synhimantus based on at least one abnormal finding on their physical examination (lethargy,...
Article
The selection of Leishmania hybrids in axenic culture was considered rare until recently, when Louradour and Ferreira et al., demonstrated that induced DNA damage facilitates genetic exchange, resulting in full genome tetraploid progenies in vitro. Meiosis-related gene homologues HAP2, GEX1, and RAD51 were found to be involved, opening new avenues...
Article
Extracellular vesicles (EVs) are small, membrane-bound “delivery trucks” that are present in the extracellular environment, including biological fluids. EVs are capable of inducing changes in the physiological status of neighboring cells through the transfer of key macromolecules, and are thought to play a role in a number of pathological processes...
Article
Full-text available
Cats that spend time outdoors and dogs are particularly at risk of exposure to ticks and the pathogens they transmit. A retrospective study on data collected through passive tick surveillance was conducted to estimate the risk of exposure to tick-borne pathogens in cats and dogs bitten by blacklegged ticks (Ixodes scapularis) in the province of Que...
Article
Full-text available
The almiramide N-methylated lipopeptides exhibit promising activity against trypanoso-matid parasites. A structure-activity relationship study has been performed to examine the influences of N-methylation and conformation on activity against various strains of leishmaniasis proto-zoan and on cytotoxicity. The synthesis and biological analysis of tw...
Preprint
Full-text available
Background The evolution of drug resistance is one of the biggest challenges in leishmaniasis and has prompted the need for new antileishmanial drugs. Repurposing of approved drugs is a faster and very attractive strategy that is gaining supporters worldwide. Different anticancer topoisomerase 1B (TOP1B) inhibitors have shown strong antileishmanial...
Poster
Full-text available
Leishmaniasis is a protozoan disease, which occurs in 12 to 15 million people worldwide and infects greater than 1 million new cases annually. The limitations in availability of effective drugs and the rise of drug resistant strains has created an urgent need for new anti-leishmanial therapy. In the light of the limitations of contemporary leishman...
Article
Full-text available
Trypanosoma cruzi, Trypanosoma brucei and Leishmania (Trypanosomatidae: Kinetoplastida) are parasitic protozoan causing Chagas disease, African Trypanosomiasis and Leishmaniases worldwide. They are vector borne diseases transmitted by triatomine bugs, Tsetse fly, and sand flies, respectively. Those diseases cause enormous economic losses and morbid...
Article
Full-text available
A mixed breed dog rescued from Morocco was presented at a Quebec veterinary practice for facial lesions. Leishmaniosis, an exotic disease caused by the zoonotic protozoan Leishmania infantum, was suspected. Genomic DNA extraction from blood samples and polymerase chain reaction (PCR) were used to confirm L. infantum parasitemia. Parasites were succ...
Article
Full-text available
Leishmaniasis (Leishmania species), sleeping sickness (Trypanosoma brucei), and Chagas disease (Trypanosoma cruzi) are devastating and globally spread diseases caused by trypanosomatid parasites. At present, drugs for treating trypanosomatid diseases are far from ideal due to host toxicity, elevated cost, limited access, and increasing rates of dru...
Article
Full-text available
The primary aim of this work was to isolate common bovine digestive tract parasites in recycled manure bedding (RMS), as well as to determine the ability of current RMS preparation procedures to eliminate these pathogens. Other objectives were to assess whether any of the aforementioned parasites could be retrieved in bulk milk from dairies using R...
Article
Background: Leishmania are sandfly-transmitted protozoan parasites that harbour within the macrophages of a mammalian host and cause leishmaniasis, a serious zoonotic disease that threatens the lives of millions worldwide. Its numerous forms (cutaneous, mucocutaneous, and visceral) are currently treated with a sparse arsenal of drugs, specifically...
Chapter
Leishmania is still a major cause of mortality and morbidity worldwide. Few efficient drugs are available, and resistance threatens actual treatments. In order to improve knowledge about the mode of action of current drugs and those in development, as well as to understand the mechanisms pertaining to their resistance, we recently described a sensi...
Article
Fruits are among the main natural sources of phenolic compounds (PC). These compounds exert important antioxidant properties primarily associated with the presence of hydroxyl groups in their molecular structure. Additionally, the antibacterial effects of fruit phenolic-rich extracts or individual PC commonly found in fruits have been an emerging r...
Article
Haemonchus contortus are gastrointestinal nematodes of the family Trichostrongylidae that naturally infect small ruminants while grazing, posing a risk to both animal health and farm profitability. Current diagnostics depend on exacting lab techniques, including manual egg counts and larval differentiation, all of which require time, effort, and sp...
Article
Full-text available
Increasing drug resistance towards first line antimony-derived compounds has forced the introduction of novel therapies in leishmaniasis endemic areas including amphotericin B and miltefosine. However, their use is threatened by the emergence and spread of drug-resistant strains. In order to discover stage-dependent resistance genes, we have adapte...
Chapter
Omics-based studies represent a major step forward in the analysis of modes of action and resistance mechanisms of drugs in Leishmania parasites, the causative agents of the leishmaniases. These are two key considerations when developing or repurposing drugs for chemotherapy against these neglected tropical diseases. The sequencing of most of the L...
Article
Full-text available
Author Summary Miltefosine and amphotericin B are two leading molecules in the fight against the vector-borne disease Leishmaniasis. We demonstrate here that different point mutations in a P-type ATPase could play an important role in resistance, not only to miltefosine, but also to amphotericin B. Furthermore, macrophage-infecting amastigotes that...
Data
SNPs deduced from the sequencing of LdiAmB1000.1 and absent from the sequencing of its Ldi263WT parent. (PDF)
Data
Characterisation of the PE species containing C19Δ in total lipid extracts from Ldi263 wt. (A) ES-MS/MS parents of 295 m/z (C19Δ acyl fragment) in negative mode (600–1000 m/z). (B-G) are daughter ion ESI-MS/MS spectra of ions identified in S6A Fig: 716, 730, 744, 774, 788, 802 m/z respectively. (PDF)
Data
Graphical representation of the different mutations identified in MT for three Leishmania drug resistant strains. The diagram includes the different conserved protein domains identified for the MT (GenBank: AAQ82704.1). (TIF)
Data
Preliminary study for the characterization of mutant L. major Friedlin AmB1080.3. (A) EC50 determination curves in the presence of miltefosine for LmF wt+mock (9.05 ± 0.89 μM), AmB1080.3+mock (54.84 ± 5.30 μM) and AmB1080.3+MT (4.43 ± 0.62 μM) cell lines over 72 h. (B) EC50 determination curves in the presence of amphotericin B for LmF wt+mock (0.1...
Data
Identification of abundance changes to the membrane lipids in AmB- and MF-resistant parasites. Negative ion ES-MS survey scans (600–1000 m/z) of total lipid extracts from Ldi263 wt (A upper panel), MF200.5 (B upper panel), AmB1000.1 (C upper panel) and AmB1000.1+MT (D upper panel). Positive ion ES-MS survey scans (600–1000 m/z) of total lipid extra...
Data
Example of total ion chromatogram of derivatised fatty acids from lipid extracts of L. infantum 263 wild-type. (A) Chromatogram including all the FAMES species with retention times spanning from 26.00 to 50.00 min for mid log phase parasites for each strain detailed in Table 1. (B) Magnification of the chromatogram for the identification of the spe...
Data
Mass spectrometric analysis of phosphatidylethanolamine species containing cyclopropyl fatty acid in Leishmania infantum. (PDF)
Data
Effect of the transfection of an episomal copy of the wild-type gene LinJ.16.1240 in the AmB1000.1 mutant background. (A) EC50 determination curves in the presence of amphotericin B for Ldi263 wt (62.01 ± 5.00 nM), AmB1000.1 (1.97 ± 0.04 μM) and AmB1000.1+LinJ.16.1240 (1.89 ± 0.11 μM) cell lines over 72 h. (B) EC50 determination curves in the prese...
Data
High resolution orbitrap mass spectrometry survey scans (600–1000 m/z) of total lipid extracts from Ldi263 wt; negative ion mode (A), positive ion mode (B). (PDF)
Data
GC-MS Sterol Analysis of Leishmania strains. TIC of chromatogram 39.50–43.50 min for (A) Ldi263, (B) MF200.5, (C) AmB1000.1, (D) AmB1000.1+MT. Numbered peaks refer to Table 4 for identification. (TIF)
Data
Estimated ploidy for Ldi263AmB1000.1 and its WT parent (Ldi263WT). (PDF)
Article
Full-text available
Innovative strategies are needed to accelerate the identification of antimicrobial drug targets and resistance mechanisms. Here we develop a sensitive method, which we term Cosmid Sequencing (or "Cos-Seq"), based on functional cloning coupled to next-generation sequencing. Cos-Seq identified >60 loci in the Leishmania genome that were enriched via...
Article
Full-text available
The use of next generation sequencing has the power to expedite the identification of drug resistance determinants and biomarkers and was applied successfully to drug resistance studies in Leishmania. This allowed the identification of modulation in gene expression, in gene dosage alterations, changes in chromosome copy numbers and single nucleotid...
Article
Full-text available
The Trypanosomatidae family, composed of unicellular parasites, causes severe vector-borne diseases that afflict human populations worldwide. Chagas disease, sleeping sickness, as well as different sorts of leishmaniases are amongst the most important infectious diseases produced by Trypanosoma cruzi, Trypanosoma brucei and Leishmania spp., respect...
Article
Full-text available
Sponges biosynthesize α-methoxylated fatty acids with unusual biophysical and biological properties and in some cases they display enhanced anticancer activities. However, the antiprotozoal properties of the α-methoxylated fatty acids have been less studied. In this work, we describe the total synthesis of (5Z,9Z)-(±)-2-methoxy-5, 9-eicosadienoic a...
Article
Full-text available
Leishmania donovani, the causative organism for visceral leishmaniasis, contains a unique heterodimeric DNA-topoisomerase IB (LdTopIB). LdTopIB is a heterodimer made up of a large subunit and a small subunit that must interact with each other to build an active enzyme able to solve the topological tensions on the DNA. As LdTopIB is located within t...
Article
Full-text available
Background: Leishmania major cutaneous leishmaniasis is an infectious zoonotic disease. It is produced by a digenetic parasite, which resides in the phagolysosomal compartment of different mammalian macrophage populations. There is an urgent need to develop new therapies (drugs) against this neglected disease that hits developing countries. The ma...
Article
2-Alkynoic fatty acids display antimycobacterial, antifungal, and pesticidal activities but their antiprotozoal activity has received little attention. In this work we synthesized the 2-octadecynoic acid (2-ODA), 2-hexadecynoic acid (2-HDA), and 2-tetradecynoic acid (2-TDA) and show that 2-ODA is the best inhibitor of the Leishmania donovani DNA to...
Article
Full-text available
Visceral leishmaniasis is an emerging neglected tropical disease (NTD) caused by the protozoan Leishmania infantum in the countries bordering the Mediterranean Basin. Currently there is no effective vaccine against this disease, and the therapeutic approach is based on toxic derivatives of SbV. Therefore, the discovery of new therapeutic targets an...
Article
L-Arginine is one of the precursor amino acids of polyamine biosynthesis in most living organisms including Leishmania parasites. L-Arginine is enzymatically hydrolyzed by arginase producing L-ornithine and urea. In Leishmania spp. and other trypanosomatids a single gene encoding arginase has been described. The product of this gene is compartmenta...
Article
Full-text available
The fatty acids (±)-2-methoxy-6Z-heptadecenoic acid (1), (±)-2-methoxy-6-heptadecynoic acid (2) and (±)-2-methoxyheptadecanoic acid (3) were synthesized and their inhibitory activity against the Leishmania DNA topoisomerase IB enzyme (LdTopIB) determined. Acids 1 and 2 were synthesized from 4-bromo-1-pentanol, the former in ten steps and in 7% over...
Article
The first total synthesis for the (Z)-16-methyl-11-heptadecenoic acid, a novel fatty acid from the sponge Dragmaxia undata, was accomplished in seven steps and in a 44% overall yield. The use of (trimethylsilyl)acetylene was key in the synthesis. Based on a previous developed strategy in our laboratory the best synthetic route towards the title com...
Article
Full-text available
The phylum Apicomplexa includes a large group of protozoan parasites responsible for a wide range of animal and human diseases. Destructive pathogens, such as Plasmodium falciparum and Plasmodium vivax, causative agents of human malaria, Cryptosporidium parvum, responsible of childhood diarrhoea, and Toxoplasma gondii, responsible for miscarriages...
Article
Full-text available
The first total syntheses of the naturally occurring acetylenic fatty acids—6-heptadecynoic acid (59% overall yield) and 6-icosynoic acid (34% overall yield)—was accomplished in four steps. Using the same synthetic sequence the naturally occurring fatty acids (6Z)-heptadecenoic acid (46% overall yield) and (6Z)-icosenoic acid (27% overall yield) we...
Article
Trypanosomatid (order Kinetoplastida)-borne neglected tropical diseases - African and American trypanosomiasis and leishmaniasis - are amongst the most devastating health threats of underdeveloped, developing and poor countries. Climatic changes due to global warming, tourism exchange and increasing migratory fluxes are re-distributing the endemic...
Article
The first total synthesis for the (Z)-17-methyl-13-octadecenoic acid was accomplished in seven steps and in a 45% overall yield. The use of (trimethylsilyl)acetylene was key in the synthesis. Based on a previous developed strategy in our laboratory the best synthetic route towards the title compound was first acetylide coupling of (trimethylsilyl)a...

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Projects (3)
Project
This project aims to characterize and exploit leishmanial extracellular vesicles in different contexts for understanding Leishmania drug-resistance emergence and spread, as well as to develop new diagnostic tools and treatments.
Project
The main objective of this project is to assess and reduce human health threats related to the presence of dogs, while promoting a less threatening environment in communities where dogs can contribute to the quality of life and human well-being.