Thursday, March 17, 2011

What's new for 'Trypanosomatids' in PubMed

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Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results
Items 1 - 9 of 9

1. Mol Genet Genomics. 2011 Mar 16. [Epub ahead of print]

Phylogenetic and genetic linkage between novel atypical dual-specificity phosphatases from non-metazoan organisms.

Romá-Mateo C, Sacristán-Reviriego A, Beresford NJ, Caparrós-Martín JA, Culiáñez-Macià FA, Martín H, Molina M, Tabernero L, Pulido R.

Centro de Investigación Príncipe Felipe, Avenida Autopista del Saler 16-3, 46013, Valencia, Spain, croma@ibv.csic.es.

Abstract

Dual-specificity phosphatases (DSPs) constitute a large protein tyrosine phosphatase (PTP) family, with examples in distant evolutive phyla. PFA-DSPs (Plant and Fungi Atypical DSPs) are a group of atypical DSPs present in plants, fungi, kinetoplastids, and slime molds, the members of which share structural similarity with atypical- and lipid phosphatase DSPs from mammals. The analysis of the PFA-DSPs from the plant Arabidopsis thaliana (AtPFA-DSPs) showed differential tissue mRNA expression, substrate specificity, and catalytic activity for these proteins, suggesting different functional roles among plant PFA-DSPs. Bioinformatic analysis revealed the existence of novel PFA-DSP-related proteins in fungi (Oca1, Oca2, Oca4 and Oca6 in Saccharomyces cerevisiae) and protozoa, which were segregated from plant PFA-DSPs. The closest yeast homolog for these proteins was the PFA-DSP from S. cerevisiae ScPFA-DSP1/Siw14/Oca3. Oca1, Oca2, Siw14/Oca3, Oca4, and Oca6 were involved in the yeast response to caffeine and rapamycin stresses. Siw14/Oca3 was an active phosphatase in vitro, whereas no phosphatase activity could be detected for Oca1. Remarkably, overexpression of Siw14/Oca3 suppressed the caffeine sensitivity of oca1, oca2, oca4, and oca6 deleted strains, indicating a genetic linkage and suggesting a functional relationship for these proteins. Functional studies on mutations targeting putative catalytic residues from the A. thaliana AtPFA-DSP1/At1g05000 protein indicated the absence of canonical amino acids acting as the general acid/base in the phosphor-ester hydrolysis, which suggests a specific mechanism of reaction for PFA-DSPs and related enzymes. Our studies demonstrate the existence of novel phosphatase protein families in fungi and protozoa, with active and inactive enzymes linked in common signaling pathways. This illustrates the catalytic and functional complexity of the expanding family of atypical dual-specificity phosphatases in non-metazoans, including parasite organisms responsible for infectious human diseases.

PMID: 21409566 [PubMed - as supplied by publisher]
2. PLoS Negl Trop Dis. 2011 Mar 8;5(3):e984.

Shotgun Sequencing Analysis of Trypanosoma cruzi I Sylvio X10/1 and Comparison with T. cruzi VI CL Brener.

Franzén O, Ochaya S, Sherwood E, Lewis MD, Llewellyn MS, Miles MA, Andersson B.

Science for Life Laboratory, Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.

Abstract

Trypanosoma cruzi is the causative agent of Chagas disease, which affects more than 9 million people in Latin America. We have generated a draft genome sequence of the TcI strain Sylvio X10/1 and compared it to the TcVI reference strain CL Brener to identify lineage-specific features. We found virtually no differences in the core gene content of CL Brener and Sylvio X10/1 by presence/absence analysis, but 6 open reading frames from CL Brener were missing in Sylvio X10/1. Several multicopy gene families, including DGF, mucin, MASP and GP63 were found to contain substantially fewer genes in Sylvio X10/1, based on sequence read estimations. 1,861 small insertion-deletion events and 77,349 nucleotide differences, 23% of which were non-synonymous and associated with radical amino acid changes, further distinguish these two genomes. There were 336 genes indicated as under positive selection, 145 unique to T. cruzi in comparison to T. brucei and Leishmania. This study provides a framework for further comparative analyses of two major T. cruzi lineages and also highlights the need for sequencing more strains to understand fully the genomic composition of this parasite.

PMID: 21408126 [PubMed - in process]
3. PLoS Negl Trop Dis. 2011 Mar 8;5(3):e980.

Mucosal Leishmaniasis Caused by Leishmania (Viannia) braziliensis and Leishmania (Viannia) guyanensis in the Brazilian Amazon.

de Oli veira Guerra JA, Prestes SR, Silveira H, Coelho LI, Gama P, Moura A, Amato V, Barbosa MG, de Lima Ferreira LC.

Tropical Medicine Foundation of Amazonas, Manaus, Amazonas, Brazil.

Abstract

BACKGROUND: Leishmania (Viannia) braziliensis is a parasite recognized as the most important etiologic agent of mucosal leishmaniasis (ML) in the New World. In Amazonia, seven different species of Leishmania, etiologic agents of human Cutaneous Leishmaniasis, have been described. Isolated cases of ML have been described for several different species of Leishmania: L. (V.) panamensis, L. (V.) guyanensis and L. (L.) amazonensis.

METHODOLOGY: Leishmania species were characterized by polymerase chain reaction (PCR) of tissues taken from mucosal biopsies of Amazonian patients who were diagnosed with ML and treated at the Tropical Medicine Foundation of Amazonas (FMTAM) in Manaus, Amazonas state, Brazil. Samples were obtained retrospectively from the pathology laboratory and prospectively from patients attending the aforementioned tertiary care unit.

RESULTS: This study reports 46 cases of ML along with their geographical origin, 30 cases caused by L. (V.) braziliensis and 16 cases by L. (V.) guyanensis. This is the first record of ML cases in 16 different municipalities in the state of Amazonas and of simultaneous detection of both species in 4 municipalities of this state. It is also the first record of ML caused by L. (V.) guyanensis in the states of Pará, Acre, and Rondônia and cases of ML caused by L. (V.) braziliensis in the state of Rondônia.

CONCLUSIONS/SIGNIFICANCE: L. (V.) braziliensis is the predominant species that causes ML in the Amazon region. However, contrary to previous studies, L. (V.) guyanensis is also a significant causative agent of ML within the region. The clinical and epidemiological expression of ML in the Manaus region is similar to the rest of the country, although the majority of ML cases are found south of the Amazon River.

PMID: 21408116 [PubMed - in process]
4. PLoS One. 2011 Mar 9;6(3):e17486.

Reactive Oxygen Species Scavenging by Catalase Is Important for Female Lutzomyia longipalpis Fecundity and Mortality.

Diaz-Albiter H, Mitford R, Genta FA, Sant'anna MR, Dillon RJ.

Vector Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.

Abstract

The phlebotomine sand fly Lutzomyia longipalpis is the most important vector of American visceral leishmaniasis (AVL), the disseminated and most serious form of the disease in Central and South America. In the natural environment, most female L. longipalpis are thought to survive for less than 10 days and will feed on blood only once or twice during their lifetime. Successful transmission of parasites occurs when a Leishmania-infected female sand fly feeds on a new host. Knowledge of factors affecting sand fly longevity that lead to a reduction in lifespan could result in a decrease in parasite transmission. Catalase has been found to play a major role in survival and fecundity in many insect species. It is a strong antioxidant enzyme that breaks down toxic reactive oxygen species (ROS). Ovarian catalase was found to accumulate in the developing sand fly oocyte from 12 to 48 hours after blood feeding. Catalase expression in ovaries as well as oocyte numbers was found to decrease with age. This reduction was not found in flies when fed on the antioxidant ascorbic acid in the sugar meal, a condition that increased mortality and activation of the prophenoloxidase cascade. RNA interference was used to silence catalase gene expression in female Lu. longipalpis. Depletion of catalase led to a significant increase of mortality and a reduction in the number of developing oocytes produced after blood feeding. These results demonstrate the central role that catalase and ROS play in the longevity and fecundity of phlebotomine sand flies.

PMID: 21408075 [PubMed - in process]
5. PLoS One. 2011 Mar 9;6(3):e16891.

Cerebral Changes Occurring in Arginase and Dimethylarginine Dimethylaminohyd rolase (DDAH) in a Rat Model of Sleeping Sickness.

Amrouni D, Meiller A, Gautier-Sauvigné S, Piraud M, Bouteille B, Vincendeau P, Buguet A, Cespuglio R.

Université Claude Bernard Lyon 1, Université de Lyon, Faculté de Médecine, EA 4170 and Plateau NeuroChem, Lyon, France.

Abstract

BACKGROUND: Involvement of nitric oxide (NO) in the pathophysiology of human African trypanosomiasis (HAT) was analyzed in a HAT animal model (rat infected with Trypanosoma brucei brucei). With this model, it was previously reported that trypanosomes were capable of limiting trypanocidal properties carried by NO by decreasing its blood concentration. It was also observed that brain NO concentration, contrary to blood, increases throughout the infection process. The present approach analyses the brain impairments occurring in the regulations exerted by arginase and N(G), N(G)-dimethylarginine dimethylaminohydrolase (DDAH) on NO Synthases (NOS). In this respect: (i) cerebral enzymatic activities, mRNA and protein expression of arginase and DDAH were determined; (ii) immunohistochemical distribution and morphometric parameters of cells expressing DDAH-1 and DDAH-2 isoforms were examined within the diencephalon; (iii) amino acid profiles relating to NOS/arginase/DDAH pathways were established.

METHODOLOGY/PRINCIPAL FINDINGS: Arginase and DDAH activities together with mRNA (RT-PCR) and protein (western-blot) expressions were determined in diencephalic brain structures of healthy or infected rats at various days post-infection (D5, D10, D16, D22). While arginase activity remained constant, that of DDAH increased at D10 (+65%) and D16 (+51%) in agreement with western-blot and amino acids data (liquid chromatography tandem-mass spectrometry). Only DDAH-2 isoform appeared to be up-regulated at the transcriptional level throughout the infection process. Immunohistochemical staining further revealed that DDAH-1 and DDAH-2 are contained within interneurons and neurons, respectively.

CONCLUSION/SIGNIFICANCE: In the brain of infected animals, the lack of change observed in arginase activity indicates that polyamine production is not enhanced. Increases in DDAH-2 isoform may contribute to the overproduction of NO. These changes are at variance with those reported in the periphery. As a whole, the above processes may ensure additive protection against trypanosome entry into the brain, i.e., maintenance of NO trypanocidal pressure and limitation of polyamine production, necessary for trypanosome growth.

PMID: 21408057 [PubMed - in process]
6. PLoS Negl Trop Dis. 2011 Mar 1;5(3):e968.

Clinical Presentation of T.b. rhodesiense Sleeping Sickness in Second Stage Patients from Tanzania and Uganda.

Kuepfer I, Hhary EP, Allan M, Edielu A, Burri C, Blum JA.

Swiss Tropical and Public Health Institute, Basel, Switzerland.

Abstract

BACKGROUND: A wide spectrum of disease severity has been described for Human African Trypanosomiasis (HAT) due to Trypanosoma brucei rhodesiense (T.b. rhodesiense), ranging from chronic disease patterns in southern countries of East Africa to an increase in virulence towards the north. However, only limited data on the clinical presentation of T.b. rhodesiense HAT is available. From 2006-2009 we conducted the first clinical trial program (Impamel III) in T.b. rhodesiense endemic areas of Tanzania and Uganda in accordance with international standards (ICH-GCP). The primary and secondary outcome measures were safety and efficacy of an abridged melarsoprol schedule for treatment of second stage disease. Based on diagnostic findings and clinical examinations at baseline we describe the clinical presentation of T.b. rhodesiense HAT in second stage patients from two distinct geographical settings in East Africa.

METHODOLOGY/PRINCIPAL FINDINGS: 138 second stage patients from Tanzania and Uganda were enrolled. Blood samples were collected for diagnosis and molecular identification of the infective trypanosomes, and T.b. rhodesiense infection was confirmed in all trial subjects. Significant differences in diagnostic parameters and clinical signs and symptoms were observed: the median white blood cell (WBC) count in the cerebrospinal fluid (CSF) was significantly higher in Tanzania (134cells/mm(3)) than in Uganda (20cells/mm(3); p<0.0001). Unspecific signs of infection were more commonly seen in Uganda, whereas neurological signs and symptoms specific for HAT dominated the clinical presentation of the disease in Tanzania. Co-infections with malaria and HIV did not influence the clinical presentation nor treatment outcomes in the Tanzanian study population.

CONCLUSIONS/SIGNIFICANCE: We describe a different clinical presentation of second stage T.b. rhodesiense HAT in two distinct geographical settings in East Africa. In the ongoing absence of sensitive diagnostic tools and safe drugs to diagnose and treat second stage T.b. rhodesiense HAT an early identification of the disease is essential. A detailed understanding of the clinical presentation of T.b. rhodesiense HAT among health personnel and affected communities is vital, and awareness of regional characteristics, as well as implications of co-infections, can support decision making and differential diagnosis.

PMID: 21407802 [PubMed - in process]
7. J Vector Borne Dis. 2011 Mar;48(1):37-40.

Pathogenicity of Metarhizium anisopliae (Metch) Sorok and Beauveria bassiana (Bals) Vuill to adult Phlebotomus duboscqi (Neveu-Lemaire) in the laboratory.

Ngumbi PM, Irungu LW, Ndegwa PN, Maniania NK.

Kenya Medical Research Institute;

Abstract

Background & objectives: Biological control of sandflies using entomopathogenic fungi is a possible alternative to the expensive synthetic chemical control. It is potentially sustainable, less hazardous, and relatively inexpensive and merits further investigations. The objective of this study was to identify the most pathogenic fungal isolate(s) to sandflies in the laboratory. Methods: Isolates of entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana were screened for their pathogenicity against Phlebotomus duboscqi. Adult flies were contaminated using the technique described by Migiro et al (2010). Briefly, flies were exposed to 0.1 g of dry conidia evenly spread on a cotton velvet cloth covering the inner side of a cylindrical plastic tube (95 mm long × 48 mm diam). In all 25 sandflies were transferred into the cylindrical tube and allowed to walk on the velvet for one minute, after which they were transferred from the velvet into the cages in Perplex. Insects in the control treatments were exposed to fungusfree velvet cloth before being transferred into similar cages. The treatments were maintained at 25 ± 2°C, 60-70% RH and 12L: 12D photoperiod. The experiment was replicated 5 times. The most pathogenic isolates were selected for further studies. Results: A total of 19 isolates were screened against adult sandflies in the laboratory. Mortality in the controls was approximately 16.8 ± 1.7 %. All the isolates were found to be pathogenic to P. duboscqi. Mortality ranged between 76.8 and 100% on all the fungal isolates tested. The lethal time taken to 50% (LT50) and 90% (LT90) mortality ranged from 3.0-7.8 days and from 5.3-16.2 days, respectively. The virulent isolates, causing mortalities of 97.5-100%, were selected for further studies. Interpretation & conclusion: The high susceptibility of sandflies to entomopathogenic fungi suggests that fungi are potential alternatives to chemical control methods. We conclude that application of entomopathogenic fungi could result in acute mortalities of sandflies and reduction of parasite transmission and subsequently, reduction of leishmaniasis risk. This method of biological control has great potential as a new strategy for leishmaniasis control.

PMID: 21406735 [PubMed - in process]
8. BMC Public Health. 2011 Mar 4;11 Suppl 2:S10.

The AFHSC-Division of GEIS Operations Predictive Surveillance Program: a multidisciplinary approach for the early detection and response to disease outbreaks.

Witt CJ, Richards AL, Masuoka PM, Foley DH, Buczak AL, Musila LA, Richardson JH, Colacicco-Mayhugh MG, Rueda LM, Klein TA, Anyamba A, Small J, Pavlin JA, Fukuda MM, Gaydos J, Russell KL; AFHSC-GEIS Predictive Surveillance Writing Group, Wilkerson RC, Gibbons RV, Jarman RG, Myint KS, Pendergast B, Lewis S, Pinzon JE, Collins K, Smith M, Pak E, Tucker C, Linthicum K, Myers T, Mansour M, Earhart K, Kim HC, Jiang J, Schnabel D, Clark JW, Sang RC, Kioko E, Abuom DC, Grieco JP, Richards EE, Tobias S, Kasper MR, Montgomery JM, Florin D, Chretien JP, Philip TL.

Armed Forces Health Surveillance Center, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. clara.witt@us.army.mil

Abstract

The Armed Forces Health Surveillance Center, Division of Global Emerging Infections Surveillance and Response System Operations (AFHSC-GEIS) initiated a coordinated, multidisciplinary program to link data sets and information derived from eco-climatic remote sensing activities, ecologic niche modeling, arthropod vector, animal disease-host/reservoir, and human disease surveillance for febrile illnesses, into a predictive surveillance program that generates advisories and alerts on emerging infectious disease outbreaks. The program's ultimate goal is pro-active public health practice through pre-event preparedness, prevention and control, and response decision-making and prioritization. This multidisciplinary program is rooted in over 10 years experience in predictive surveillance for Rift Valley fever outbreaks in Eastern Africa. The AFHSC-GEIS Rift Valley fever project is based on the identification and use of disease-emergence critical detection points as reliable signals for increased outbreak risk. The AFHSC-GEIS predictive surveillance program has formalized the Rift Valley fever project into a structured template for extending predictive surveillance capability to other Department of Defense (DoD)-priority vector- and water-borne, and zoonotic diseases and geographic areas. These include leishmaniasis, malaria, and Crimea-Congo and other viral hemorrhagic fevers in Central Asia and Africa, dengue fever in Asia and the Americas, Japanese encephalitis (JE) and chikungunya fever in Asia, and rickettsial and other tick-borne infections in the U.S., Africa and Asia.

PMID: 21388561 [PubMed - in process]
9. Wien Klin Wochenschr. 2010 Oct;122 Suppl 3:81-6.

Host preference of tsetse: an important tool to appraise the Nagana risk of cattle in the cotton zone of Mali.

Hoppenheit A, Steuber S, Bauer B, Ouma EM, Diall O, Zessin KH, Clausen PH.

Freie Universität Berlin, Institute for Parasitology and Tropical Veterinary Medicine, Berlin, Germany. Antje_hoppenheit@yahoo.de

Abstract

Nagana, a vector-borne epizootic caused by trypanosomes, severely constrains the use of draught animals in the cotton zone of south-eastern Mali. The disease causes considerable economic losses for the local farmers due to high mortality and morbidity ensuing productivity losses. Nagana is routinely controlled by the use of trypanocides and an overreliance on their use throughout past decades resulted in multiple drug resistance of trypanosomes in most parts of West Africa's cotton belt. Designing alternative, effective vector control strategies requires an identification of the preferred hosts of tsetse flies through blood meal analysis as a prerequisite for estimating infection risk. A survey was, therefore, conducted between November 2008 and April 2009, catching 474 Glossina species which were dissected. Blood meals were smeared on filter paper (Whatman(®)-FTA-Cards) for laboratory analysis. DNA extractions and amplification using universal vertebrate cytochrome b primers of 120 assorted samples detected 74 DNA-containing specimens. The subsequent use of cattle-specific primers yielded 52 visible amplicons in the gel electrophoresis. Sequencing and BLASTN(®) analysis of the remaining samples revealed 19 blood meals matching with existing sequences of the human genome in Genbank(®). Two samples originated from crocodiles whereas one was unidentifiable.

PMID: 20924694 [PubMed - indexed for MEDLINE]
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