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Sent on Saturday, 2012 February 11Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Clin Vaccine Immunol. 2012 Feb 8. [Epub ahead of print]Killed but metabolically active Leishmania as a novel whole-cell vaccine for visceral leishmaniasis.Birnbaum R, Haskell J, Vanchinathan V, Greger S, Narayan R, Chang PL, Tran TA, Hickerson SM, Beverley SM, Wilson ME, Bruhn KW, Craft N.SourceLos Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502 USA. AbstractThere are currently no effective vaccines for visceral leishmaniasis, the second most deadly parasitic infection in the world. Here we describe a novel whole-cell vaccine approach using Leishmania infantum chagasi promastigotes treated with the psoralen compound amotosalen (S-59) and low doses of ultraviolet A radiation. This treatment generates permanent, covalent DNA crosslinks within parasites, and results in Leishmania organisms termed killed but metabolically active (KBMA). In this report, we characterize the in vitro growth characteristics of both KBMA-L. major and KBMA-L. infantum chagasi (KBMA-Lic). Concentrations of S-59 that generate optimally attenuated parasites were identified. Like live L. infantum chagasi, KBMA-Lic parasites were able to initially enter liver cells in vivo after intravenous infection. However, whereas live L. infantum chagasi infection leads to hepatosplenomegaly in mice after six months, KBMA-Lic were undetectable in the organs of mice at this time point. In vitro, KBMA-Lic retained the ability to enter macrophages and induce nitric oxide production. These characteristics of KBMA-Lic correlated with the ability to prophylactically protect mice via subcutaneous vaccination at levels similar to vaccination with live, virulent organisms. Splenocytes from mice vaccinated with either live L. infantum chagasi or KBMA-Lic displayed similar cytokine patterns in vitro. These results suggest that KBMA technology is a potentially safe and effective novel vaccine strategy against the intracellular protozoan L. infantum chagasi. This approach may represent a new method for whole-cell vaccination against other complex intracellular pathogens. |
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| 2. | BMC Microbiol. 2012 Feb 9;12(1):22. [Epub ahead of print]A comparison of two distinct murine macrophage gene expression profiles in response to Leishmania amazonensis infection.Probst CM, Silva RA, Menezes JP, Almeida TF, Gomes IN, Dallabona AC, Ozaki LS, Buck GA, Pavoni DP, Krieger MA, Veras PS.AbstractABSTRACT: BACKGROUND:The experimental murine model of leishmaniasis has been widely used to characterize the immune response against Leishmania. CBA mice develop severe lesions, while C57BL/6 present small chronic lesions under L. amazonensis infection. Employing a transcriptomic approach combined with biological network analysis, the gene expression profiles of C57BL/6 and CBA macrophages, before and after L. amazonensis infection in vitro, were compared. These strains were selected due to their different degrees of susceptibility to this parasite. RESULTS:The genes expressed by C57BL/6 and CBA macrophages, before and after infection, differ greatly, both with respect to absolute number as well as cell function. Uninfected C57BL/6 macrophages express genes involved in the deactivation pathway of macrophages at lower levels, while genes related to the activation of the host immune inflammatory response, including apoptosis and phagocytosis, have elevated expression levels. Several genes that participate in the apoptosis process were also observed to be up-regulated in C57BL/6 macrophages infected with L. amazonensis, which is very likely related to the capacity of these cells to control parasite infection. By contrast, genes involved in lipid metabolism were found to be up-regulated in CBA macrophages in response to infection, which supports the notion that L. amazonensis probably modulates parasitophorous vacuoles in order to survive and multiply in host cells. CONCLUSION:The transcriptomic profiles of C57BL/6 macrophages, before and after infection, were shown to be involved in the macrophage pathway of activation, which may aid in the control of L. amazonensis infection, in contrast to the profiles of CBA cells. |
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| 3. | Trans R Soc Trop Med Hyg. 2012 Feb 7. [Epub ahead of print]Prevalence of antibodies against three species of Leishmania (L. mexicana, L. braziliensis, L. infantum) and possible associated factors in dogs from Mérida, Yucatán, Mexico.Arjona-Jiménez G, Villegas N, López-Céspedes A, Marín C, Longoni SS, Bolio-González ME, Rodríguez-Vivas RI, Sauri-Arceo CH, Sánchez-Moreno M.SourceCampus de Ciencias Biológicas y Agropecuarias, Universidad Autónoma de Yucatán, México. Km 15.5 Carretera Mérida-Xmatkuil, Mérida, Yucatán, México. AbstractLeishmania spp. has been recorded in humans and in dogs, and numerous studies have demonstrated that dogs act as reservoirs for visceral leishmaniasis. The objective of this study was to determine the prevalence of three species of the Leishmania genus and possible associated factors in sera of 218 dogs from two different populations in Mérida, Yucatán (Mexico). The sera were analyzed to detect antibodies against L. mexicana, L. braziliensis, and L. infantum using the superoxide dismutase- enzyme-linked immunosorbent assay (SOD-ELISA) and Western blot as confirmation. The Fe-SOD excreted was used as the antigenic fraction for the three Leishmania species. The prevalence values found were 30.2% (L. mexicana), 8.2% (L. braziliensis), and 11.9% (L. infantum), with L. mexicana seroprevalence being greater than L. braziliensis and L. infantum (p<0.05). Five percent (11/218) of the dogs showed antibodies against L. mexicana/L. braziliensis, 5.5% (12/218) with L. mexicana/L. infantum and 1.8% (4/218) with L. mexicana/L. braziliensis/L. infantum. No relationship (p>0.05) was found between antibodies against L. mexicana and breed, age, physical condition, or cutaneous lesions in dogs. This study provides evidence of antibodies against L. mexicana, L. braziliensis and L. infantum in dog populations from Mérida, Mexico. Copyright © 2012 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved. |
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| 4. | PLoS Comput Biol. 2011 Oct;7(10):e1002178. Epub 2011 Oct 13.Large-scale conformational changes of Trypanosoma cruzi proline racemase predicted by accelerated molecular dynamics simulation.de Oliveira CA, Grant BJ, Zhou M, McCammon JA.SourceDepartments of Chemistry and Biochemistry, Howard Hughes Medical Institute, Center for Theoretical Biological Physics, University of California, San Diego, La Jolla, California, United States of America. cesar@mccammon.ucsd.edu AbstractChagas' disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is a life-threatening illness affecting 11-18 million people. Currently available treatments are limited, with unacceptable efficacy and safety profiles. Recent studies have revealed an essential T. cruzi proline racemase enzyme (TcPR) as an attractive candidate for improved chemotherapeutic intervention. Conformational changes associated with substrate binding to TcPR are believed to expose critical residues that elicit a host mitogenic B-cell response, a process contributing to parasite persistence and immune system evasion. Characterization of the conformational states of TcPR requires access to long-time-scale motions that are currently inaccessible by standard molecular dynamics simulations. Here we describe advanced accelerated molecular dynamics that extend the effective simulation time and capture large-scale motions of functional relevance. Conservation and fragment mapping analyses identified potential conformational epitopes located in the vicinity of newly identified transient binding pockets. The newly identified open TcPR conformations revealed by this study along with knowledge of the closed to open interconversion mechanism advances our understanding of TcPR function. The results and the strategy adopted in this work constitute an important step toward the rationalization of the molecular basis behind the mitogenic B-cell response of TcPR and provide new insights for future structure-based drug discovery. |
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| 5. | Insect Mol Biol. 2011 Dec;20(6):775-86. doi: 10.1111/j.1365-2583.2011.01107.x. Epub 2011 Sep 12.Prolixicin: a novel antimicrobial peptide isolated from Rhodnius prolixus with differential activity against bacteria and Trypanosoma cruzi.Ursic-Bedoya R, Buchhop J, Joy JB, Durvasula R, Lowenberger C.SourceSimon Fraser University, Department of Biological Sciences, 8888 University Drive, Burnaby, BC, Canada. AbstractWe identified and characterized the activity of prolixicin, a novel antimicrobial peptide (AMP) isolated from the hemipteran insect, Rhodnius prolixus. Sequence analysis reveals one region of prolixicin that may be related to the diptericin/attacin family of AMPs. Prolixicin is an 11-kDa peptide containing a putative 21 amino acid signal peptide, two putative phosphorylation sites and no glycosylation sites. It is produced by both adult fat body and midgut tissues in response to bacterial infection of the haemolymph or the midgut. Unlike most insect antibacterial peptides, the prolixicin gene does not seem to be regulated by NF-κB binding sites, but its promoter region contains several GATA sites. Recombinant prolixicin has strong activity against the Gram-negative bacterium Escherichia coli and differential activity against several Gram-negative and Gram-positive bacteria. No significant toxicity was demonstrated against Trypanosoma cruzi, the human parasite transmitted by R. prolixus. © 2011 The Authors. Insect Molecular Biology © 2011 The Royal Entomological Society. |
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| 6. | Mem Inst Oswaldo Cruz. 2011 Jun;106(4):445-50.Distribution and infection of triatomines (Hemiptera: Reduviidae) by Trypanosoma cruzi in the state of Michoacán, Mexico.Martínez-Ibarra JA, Valencia-Navarro I, León-Saucedo S, Ibáñez-Cervantes G, Bustos-Saldaña R, Montañez-Valdez OD, Cervantes Díaz OI, Nogueda-Torres B.SourceCentro Universitario del Sur, Universidad de Guadalajara, Jalisco, México. aibarra@cusur.udg.mx AbstractAn entomological study of triatomine species was carried out to assess their prevalence in 10 localities of the state of Michoacán, Mexico. Entomological indices were calculated to estimate the risk for vector-borne transmission of Trypanosoma cruzi to the human population in this area. Four triatomine species (Triatoma barberi, Triatoma dimidiata, Meccus pallidipennis and Meccus longipennis) were collected from the study area. This is the first report of M. longipennis and T. dimidiata in Michoacán. M. pallidipennis was significantly (p < 0.05) more abundant than any of the other species collected in the study area. Infection indices were greater than 50% for each of the four collected triatomine species. Significantly more triatomines were collected from intradomiciliary areas than from peridomiciliary or sylvatic areas. Infestation, crowding and density indices were low, whereas colonisation indices were high in five localities. The current vectorial conditions in the study area require continuous entomological and serological surveillance to diminish the risk of T. cruzi transmission to human populations. |
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| 7. | Mem Inst Oswaldo Cruz. 2011 Jun;106(4):416-23.A high corticosterone/DHEA-s ratio in young rats infected with Tryp anosoma cruzi is associated with increased susceptibility.Pérez AR, Bertoya AA, Revelli S, García F.SourceInstituto de Inmunología, Facultad de Ciencias Médicas de Rosario, Universidad Nacional de Rosario, Rosario, Argentina. AbstractWe have previously established that young male rats are more susceptible to the effects of Trypanosoma cruzi infection than adult rats. To explore underlying age-associated differences in disease outcome, we simultaneously assessed hormone levels and cytokine release throughout the acute infection period in young and adult rats infected with T. cruzi. Young rats were inoculated with 1 x 10(6) and adult rats with 7 x 10(6) blood trypomastigotes, according to their relative body weight. At zero, seven, 14, 21 and 28 days after infection, blood was collected for the determination of gonadal and adrenal hormones, tumor necrosis factor α (TNF-α), interleukin (IL)-10 and specific IgM and IgG subtypes. Young animals displayed significantly higher parasitaemia values and an endocrine pattern that was characterised by elevated values in corticosterone (CT) and the CT/dehydroepiandrosterone-sulfate ratio, which favours immunosuppression and susceptibility. In contrast, adult male rats were able to restrict the parasite burden, which likely resulted from increased IgG antibody synthesis and oestradiol levels. Adult rats also showed a reduced TNF-α/IL-10 ratio and less tissue damage. We conclude that young animals exhibited increased vulnerability to T. cruzi infection compared with adults and this is associated with an unsuitable immunoendocrine milieu. |
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| 8. | Curr Pharm Des. 2011;17(20):2074-99.The uniqueness of the Trypanosoma cruzi mitochondrion: opportunities to ident ify new drug target for the treatment of Chagas disease.Lisvane Silva P, Mantilla BS, Barisón MJ, Wrenger C, Silber AM.SourceDepartamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brasil. AbstractTrypanosoma cruzi is the causative agent of Chagas' disease, which affects some 8 - 10 million people in the Americas. The only two drugs approved for the etiological treatment of the disease in humans were launched more than 40 years ago and have serious drawbacks. In the present work, we revisit the unique characteristics of T. cruzi mitochondria and mitochondrial metabolism. The possibility of taking advantage of these peculiarities to target new drugs against this parasite is also discussed. |
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| 9. | ChemMedChem. 2011 Sep 5;6(9):1581-6. doi: 10.1002/cmdc.201100189. Epub 2011 Jun 15.Development of antitrypanosomal and antiplasmodial nonpeptidic cysteine protease inhibitors based on N-protected-guanidino-furan and -pyrrole building blocks.Langolf S, Machon U, Ehlers M, Sicking W, Schirmeister T, Büchhold C, Gelhaus C, Rosenthal PJ, Schmuck C.SourceInstitute of Organic Chemistry, University of Duisburg-Essen, Universitätstrasse 7, 45141 Essen, Germany. |
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