A5083487513- Research on Leishmaniasis Studies
- Trypanosoma species research and implications
- Parasites and Host Interactions
- Salmonella and Campylobacter epidemiology
- Vibrio bacteria research studies
- Innovation and Socioeconomic Development
- Bacteriophages and microbial interactions
- Escherichia coli research studies
- CRISPR and Genetic Engineering
- Child Nutrition and Water Access
- Health and Conflict Studies
- RNA and protein synthesis mechanisms
- Microbial Community Ecology and Physiology
- Leptospirosis research and findings
- Polar Research and Ecology
- Cassava research and cyanide
- Bacterial Genetics and Biotechnology
McGill University
2015-2025
McGill Genome Centre
2024
Leishmaniasis is a neglected tropical disease caused by Leishmania protozoa transmitted infected sand flies. Vaccination through leishmanization with live major has been used successfully but no longer practiced because it resulted in occasional skin lesions. A second generation described here using CRISPR genome edited L. strain (LmCen-/-). Notably, LmCen-/- genetically engineered centrin gene knock-out mutant that antibiotic resistant marker free and does not have detectable off-target...
CRISPR-Cas9-mediated genome editing has recently been adapted for Leishmania spp. parasites, the causative agents of human leishmaniasis. We have optimized this genome-editing tool by selecting cells with CRISPR-Cas9 activity through cotargeting miltefosine transporter gene; mutation gene leads to resistance. This strategy integrated into a triple guide RNA (gRNA) expression vector was used delete all 11 copies A2 multigene family; not previously possible traditional gene-targeting method....
Leishmaniasis is a neglected tropical disease transmitted by infected sandflies that results in diverse human pathologies contingent on the species of Leishmania. Leishmania donovani causes highly virulent fatal visceral leishmaniasis, whereas major and tropica cause less virulent, cutaneous which infection remains skin at site sandfly bite. The aim this study was to investigate genetic basis for emergence L strains leishmaniasis instead Sri Lanka.All available sequencing data samples from...
Abstract Leishmaniasis is widely regarded as a vaccine-preventable disease, but the costs required to reach pivotal Phase 3 studies and uncertainty about which candidate vaccines should be progressed into human significantly limits progress in vaccine development for this neglected tropical disease. Controlled infection models (CHIMs) provide pathway accelerating more fully understand disease pathogenesis correlates of protection. Here, we describe isolation, characterization GMP manufacture...
Leishmaniasis is a neglected protozoan disease affecting over 12 million people globally with no approved vaccines for human use. New World cutaneous leishmaniasis (CL) caused by L. mexicana characterized the development of chronic non-healing skin lesions. Using CRISPR/Cas9 technique, we have generated live attenuated centrin knockout (LmexCen-/-) parasites. Centrin cytoskeletal protein important cellular division in eukaryotes and, Leishmania, required only intracellular amastigote...
Leishmania donovani is responsible for visceral leishmaniasis, a neglected and lethal parasitic disease with limited treatment options no vaccine. The study of L. has been hindered by the lack high-quality reference genome this can impact experimental outcomes including identification virulence genes, drug targets vaccine development. We therefore generated complete assembly deep sequencing using combination second generation (Illumina) third (PacBio) technologies. Compared to current...
Leishmaniasis is a neglected tropical disease endemic in over 90 countries. The has two main pathologies; cutaneous leishmaniasis (CL) that generally self-heals, and visceral (VL) fatal if untreated. majority of VL cases, concentrated on the Indian subcontinent (ISC) East Africa, are caused by
Dogs are the main reservoir host of Leishmania infantum, etiological agent zoonotic visceral leishmaniasis (ZVL). An effective vaccine against Canine Visceral Leishmaniasis (CVL) will help control and elimination ZVL. In this study, we evaluated in dogs safety, immunogenicity, efficacy a live attenuated major Centrin gene-deleted (LmCen−/−) as vaccine. Two doses (106 or 107) LmCen−/− were administered intradermally prime-boost regimen. Both induced equally high level IgG anti-Leishmania...
Understanding the drivers of horizontal gene transfer (HGT) is a key question in microbial evolution. While co-occurring taxa have long been appreciated to undergo HGT more often, this association confounded with other factors, most notably their phylogenetic distance. To disentangle these we analyzed 15,339 isolate and metagenome-assembled marine genomes. We identified events across genomes, enrichments for functions previously shown be prone HGT. By mapping metagenomic reads from 1,862...
The clinical manifestation of leishmaniasis has historically been determined by the Leishmania species involved. However, recent emergence novel lineages caused atypical pathologies. We isolated and characterized 2 new donovani parasites causing cutaneous in Himachal Pradesh, India.
Leishmaniasis is one of the top neglected tropical diseases with significant morbidity and mortality in low middle-income countries (LMIC). However, this disease also spreading developed world. Currently, there a lack effective strategies to control disease. Vaccination can be an measure leishmaniasis has potential achieve elimination. Recently, we have generated centrin gene-deleted new world L. mexicana (LmexCen-/-) parasites using CRISPR/Cas9 showed that they protect mice against...
ABSTRACT Iron acquisition at the outer membrane (OM) of Gram-negative bacteria is powered by proton motive force (PMF) cytoplasmic (CM), harnessed CM-embedded complex ExbB, ExbD, and TonB. Its stoichiometry, ensemble structural features, mechanism action are unknown. By panning combinatorial phage libraries, periplasmic regions dimerization between ExbD TonB were predicted. Using overexpression full-length His 6 -tagged exbB-exbD S-tagged tonB , we purified detergent-solubilized complexes...
CRISPR-Cas9 is an RNA guided endonuclease derived from the bacterium Streptococcus pyogenes. Due to its simplicity, versatility, and high efficiency, it has been widely used for genome editing in a variety of organisms including protozoan parasite Leishmania, causative agent human leishmaniasis. Compared traditional homologous recombination gene targeting method, shown be more efficient method delete or disrupt Leishmania genes, generate point mutations, add tags endogenous genes. Notably,...
Visceral leishmaniasis (VL), caused by Leishmania donovani complex parasites, is a neglected parasitic disease that generally fatal if untreated. Despite decades of research to develop sensitive VL diagnostic test, definitive diagnosis still mainly relies on the visualization parasite in aspirates from spleen, liver or bone marrow, an invasive and dangerous process with variable sensitivity. A assay can detect antigen blood samples will help confirm cause, cure recurrence VL. In this study,...
Leishmaniasis is a widespread neglected tropical disease transmitted by infected sand flies resulting in either benign cutaneous infection or fatal visceral disease. Leishmania donovani the principal species responsible for leishmaniasis, yet an atypical L. has become attenuated several countries including Sri Lanka and causes leishmaniasis. Previous studies have identified 91 genes altered compared to typical associated mutations RagC Raptor that are part of eukaryotic conserved TOR pathway...
The leishmanin skin test was used for almost a century to detect exposure and immunity Leishmania, the causative agent of leishmaniasis, major neglected tropical disease. Due lack antigen intradermal injection, is no longer available. As leishmaniasis control programs are advancing new vaccines entering clinical trials, it essential re-introduce test. Here we establish Leishmania donovani strain describe production, under Good Laboratory Practice conditions, soluble induce in animal models...
ABSTRACT Vibrio cholerae O1 causes the diarrheal disease cholera, and small intestine is site of active infection. During cholera toxin secreted from V. induces a massive fluid influx into intestine, which vomiting diarrhea. Typically, genomes are sequenced bacteria passed in stool, but rarely vomit, that may more closely represents We hypothesized population bottlenecks along gastrointestinal tract would result reduced genetic variation stool compared to vomit. To test this, we ten patients...
The protozoan parasite Leishmania donovani is a causative agent of the neglected tropical disease known as visceral leishmaniasis, which can be lethal when untreated. Studying viru-lence factors crucial in determining how causes and identifying new targets for treatment. One potential virulence factor L. donovani’s abundantly secreted protein: acid phosphatase (SAcP). Whole-genome analysis revealed that sacp gene was present three copies wild type donovani. Using CRISPR-Cas9 editing; we...
Abstract Two circular chromosomes are a defining feature of the family Vibrionaceae , including pathogen Vibrio cholerae with rare reports isolates single, fused chromosome. Here we report chromosome fusions in clinical V. O1 isolates, several independent fusion events stable enough to be transmitted between patients within household. Fusion occurs 12 kilobase-pair homologous sequence shared two chromosomes, which may lead reversible chromosomal fusion.
ABSTRACT Vibrio cholerae O1 causes the diarrheal disease cholera, and small intestine is site of active infection. During cholera toxin secreted from V. induces a massive fluid influx into intestine, which vomiting diarrhea. Typically, genomes are sequenced bacteria passed in stool, but rarely vomit, that may more closely represents We hypothesized population bottlenecks along gastrointestinal tract would result reduced genetic variation stool compared to vomit. To test this, we 10 patients...
Cholera is a diarrhoeal disease caused by
Abstract Background Leishmaniasis is a widespread neglected tropical disease present in over 90 countries with diverse pathologies associated different species of Leishmania parasites transmitted by infected sand flies. donovani causes visceral leishmaniasis, highly virulent fatal infection the organs. major and tropica cause less cutaneous leishmaniasis where remains skin at site sandfly bite. A molecular epidemiological question why some variants L. Sri Lanka rather than typical disease....