Visceral Leishmaniasis (VL) is a parasitic disease caused by the protozoan parasite Leishmania donovani. Resistance to pentavalent antimonials (SbV), the mainstay therapy for leishmaniasis is now a major concern, due to emergence of drug resistance. Hence, understanding the underlying mechanism of resistance to antimonials is required. Here we used quantitative mass spectrometery to identify global proteome differences between antimony-susceptible/-resistant isolates. We detected modification of expression of proteins involved in the key metabolic pathways. Comparative proteomic analysis indicated increase in glycolysis in the antimony-resistant isolates. Elevated expression of stress related proteins implicated in oxidative stress was observed in the resistant parasites. Most importantly, we observed upregulation of proteins that may have a role in intracellular survival of the parasite in the resistant isolates. The identified parasite proteins could serve as surrogate markers for resistance or susceptibility and would also help in understanding the underlying mechanism of resistance to antimonials.
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http://dx.doi.org/10.1016/j.molbiopara.2011.06.004 | DOI Listing |
J Physiol
January 2025
Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada.
Here we characterize seven Cx30.3 gene variants (R22H, S26Y, P61R, C86S, E99K, T130M and M190L) clinically associated with the rare skin disorder erythrokeratodermia variabilis et progressiva (EKVP) in tissue-relevant and differentiation-competent rat epidermal keratinocytes (REKs). We found that all variants, when expressed alone or together with wildtype (WT) Cx30.
View Article and Find Full Text PDFBlood Coagul Fibrinolysis
December 2024
Department of Hematology, The Second Affiliated Hospital, Chongqing Medical University, Jiangnan, Chongqing, China.
Background: Congenital factor VII (FVII) deficiency is a genetic disorder characterized by decreased FVII activity, which sometimes leads to fatal bleeding. Numerous variants have been found in FVII deficiency, but mutations vary among patients. Each mutation deserves further exploration for each patient at risk of bleeding.
View Article and Find Full Text PDFMicrobiol Spectr
January 2025
Faculty of Chemistry, Biotechnology and Food Science, NMBU - Norwegian University of Life Sciences, Ås, Norway.
Unlabelled: a natural inhabitant of the human body, is a promising candidate vehicle for vaccine delivery. An obstacle in developing bacterial delivery vehicles is generating a production strain that lacks antibiotic resistance genes and contains minimal foreign DNA. To deal with this obstacle, we have constructed a finetuned, inducible two-plasmid CRISPR/Cas9-system for chromosomal gene insertion in .
View Article and Find Full Text PDFJ Virol
January 2025
Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
The common cold coronaviruses are a source of ongoing morbidity and mortality particularly among elderly and immunocompromised individuals. While cross-reactive immune responses against multiple coronaviruses have been described following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination, it remains unclear if these confer any degree of cross-protection against the common cold coronaviruses. A recombinant fowl adenovirus vaccine expressing the SARS-CoV-2 spike protein (FAdV-9-S19) was generated, and protection from SARS-CoV-2 challenge was shown in K18-hACE2 mice.
View Article and Find Full Text PDFJ Bacteriol
January 2025
Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada.
Unlabelled: Type IV pili (T4P) are important virulence factors that allow bacteria to adhere to and rapidly colonize their hosts. T4P are primarily composed of major pilins that undergo cycles of extension and retraction and minor pilins that initiate pilus assembly. Bacteriophages use T4P as receptors and exploit pilus dynamics to infect their hosts.
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