Saturday, November 19, 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. PLoS One. 2011;6(11):e27634. Epub 2011 Nov 11.

The Repetitive Cytoskeletal Protein H49 of Trypanosoma cruzi Is a Calpain-Like Protein Located at the Flagellum Attachment Zone.

Galetović A, Souza RT, Santos MR, Cordero EM, Bastos IM, Santana JM, Ruiz JC, Lima FM, Marini MM, Mortara RA, da Silveira JF.

Source

Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, São Paulo, Brasil.

Abstract

BACKGROUND:

Trypanosoma cruzi has a single flagellum attached to the cell body by a network of specialized cytoskeletal and membranous connections called the flagellum attachment zone. Previously, we isolated a DNA fragment (clone H49) which encodes tandemly arranged repeats of 68 amino acids associated with a high molecular weight cytoskeletal protein. In the current study, the genomic complexity of H49 and its relationships to the T. cruzi calpain-like cysteine peptidase family, comprising active calpains and calpain-like proteins, is addressed. Immunofluorescence analysis and biochemical fractionation were used to demonstrate the cellular location of H49 proteins.

METHODS AND FINDINGS:

All of H49 repeats are associated with calpain-like sequences. Sequence analysis demonstrated that this protein, now termed H49/calpain, consists of an amino-terminal catalytic cysteine protease domain II, followed by a large region of 68-amino acid repeats tandemly arranged and a carboxy-terminal segment carrying the protease domains II and III. The H49/calpains can be classified as calpain-like proteins as the cysteine protease catalytic triad has been partially conserved in these proteins. The H49/calpains repeats share less than 60% identity with other calpain-like proteins in Leishmania and T. brucei, and there is no immunological cross reaction among them. It is suggested that the expansion of H49/calpain repeats only occurred in T. cruzi after separation of a T. cruzi ancestor from other trypanosomatid lineages. Immunofluorescence and immunoblotting experiments demonstrated that H49/calpain is located along the flagellum attachment zone adjacent to the cell body.

CONCLUSIONS:

H49/calpain contains large central region composed of 68-amino acid repeats tandemly arranged. They can be classified as calpain-like proteins as the cysteine protease catalytic triad is partially conserved in these proteins. H49/calpains could have a structural role, namely that of ensuring that the cell body remains attached to the flagellum by connecting the subpellicular microtubule array to it.

PMID:
22096606
[PubMed - in process]
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2. PLoS One. 2011;6(11):e27303. Epub 2011 Nov 11.

The Structural Basis of Localizing Polo-Like Kinase to the Flagellum Attachment Zone in Trypanosoma brucei.

Sun L, Wang CC.

Source

Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, United States of America.

Abstract

The polo-like kinase in the deep branching eukaryote Trypanosoma brucei (TbPlk) has many unique features. Unlike all the other polo-like kinases known to associate with the nucleus and controlling both mitosis and cytokinesis, TbPlk localizes to the flagellum attachment zone (FAZ) and regulates only cytokinesis in T. brucei. TbPlk was, however, previously found capable of complementing all the multiple Plk (Cdc5) functions in Saccharomyces cerevisiae, indicating that it has acquired all the functions of Cdc5. In the present study, Cdc5 tagged with an enhanced yellow fluorescence protein (EYFP) localized exclusively in the FAZ of T. brucei, suggesting that the unusual localization and limited function of TbPlk are probably attributed to the particular environment in T. brucei cells. Structural basis for the FAZ localization of TbPlk was further investigated with TbPlk and TbPlk mutants tagged with EYFP and expressed in T. brucei. The results indicated that a kinase-inactive mutant N169A and a TbPlk mutant with the entire kinase domain (KD) deleted both localized to the FAZ. Substantial association with FAZ was also maintained when one of the two polo-boxes (PB1 or 2) or the linker region between them was deleted from TbPlk. But a deletion of both polo-boxes led to a complete exclusion of the protein from FAZ. All the deletion mutants retained the kinase activity, further indicating that the TbPlk kinase function does not play a role for FAZ localization. The two polo boxes in TbPlk are most likely instrumental in localizing the protein to FAZ through potential interactions with certain FAZ structural component(s). A putative cryptic bipartite nuclear targeting signal was identified in TbPlk, which was capable of directing TbPlk into the nucleus when either the kinase activity was lost or the PB1 was deleted from the protein.

PMID:
22096549
[PubMed - in process]
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3. PLoS One. 2011;6(11):e26890. Epub 2011 Nov 11.

A Novel Rho-Like Protein TbRHP Is Involved in Spindle Formation and Mitosis in Trypanosomes.

Abbasi K, Dubois KN, Dacks JB, Field MC.

Source

Department of Pathology, University of Cambridge, Cambridge, United Kingdom.

Abstract

BACKGROUND:

In animals and fungi Rho subfamily small GTPases are involved in signal transduction, cytoskeletal function and cellular proliferation. These organisms typically possess multiple Rho paralogues and numerous downstream effectors, consistent with the highly complex contributions of Rho proteins to cellular physiology. By contrast, trypanosomatids have a much simpler Rho-signaling system, and the Trypanosoma brucei genome contains only a single divergent Rho-related gene, TbRHP (Tb927.10.6240). Further, only a single RhoGAP-like protein (Tb09.160.4180) is annotated, contrasting with the >70 Rho GAP proteins from Homo sapiens. We wished to establish the function(s) of TbRHP and if Tb09.160.4180 is a potential GAP for this protein.

METHODS/FINDINGS:

TbRHP represents an evolutionarily restricted member of the Rho GTPase clade and is likely trypanosomatid restricted. TbRHP is expressed in both mammalian and insect dwelling stages of T. brucei and presents with a diffuse cytoplasmic location and is excluded from the nucleus. RNAi ablation of TbRHP results in major cell cycle defects and accumulation of multi-nucleated cells, coinciding with a loss of detectable mitotic spindles. Using yeast two hybrid analysis we find that TbRHP interacts with both Tb11.01.3180 (TbRACK), a homolog of Rho-kinase, and the sole trypanosome RhoGAP protein Tb09.160.4180, which is related to human OCRL.

CONCLUSIONS:

Despite minimization of the Rho pathway, TbRHP retains an important role in spindle formation, and hence mitosis, in trypanosomes. TbRHP is a partner for TbRACK and an OCRL-related trypanosome Rho-GAP.

PMID:
22096505
[PubMed - in process]
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4. Rev Soc Bras Med Trop. 2011 Nov 21. pii: S0037-86822011005000059. [Epub ahead of print]

Risk factors for Leishmania chagasi infection in an endemic area in Raposa, State of Maranhão, Brazil.

Ponte CB, Souza NC, Cavalcante MN, Barral AM, Aquino DM, Caldas AD.

Source

Departamento de Enfermagem, Universidade Federal do Maranhão, São Luis, MA.

Abstract

INTRODUCTION:

Infection with Leishmania chagasi is the most common clinical presentation for visceral leishmaniaisis in endemic areas. The municipality of Raposa is an endemic area in State of Maranhão, Brazil, and have had registration cases of visceral leishmaniasis disease. For this reason, a cross- sectional study was conducted to evaluate the risk factors for infection with L. chagasi detected by Montenegro skin test.

METHODS:

The sample comprised 96% of the inhabitants of the villages of Maresia, Pantoja, and Marisol located in the municipality of Raposa, corresponding to 1,359 subjects. Data were collected using a questionnaire. Univariate and multivariate logistic regression models were applied to evaluate the association between the variables studied and infection of L. chagasi.

RESULTS:

The variables associated with infection upon nonadjusted analysis were a straw roof, mud walls, floors of beaten earth, presence of sand flies inside or outside of the dwelling, and bathing outdoors. Adjusted analysis showed that the presence of sand flies inside/outside the dwelling was a risk factor, and age younger than 10 years was a protective factor against asymptomatic infection.

CONCLUSIONS:

The results highlight the extent to which precarious living conditions of the population strengthen the epidemiological chain of visceral leishmaniasis.

PMID:
22094705
[PubMed - as supplied by publisher]
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5. Trans R Soc Trop Med Hyg. 2011 Nov 15. [Epub ahead of print]

Human African trypanosomiasis in Angola: clinical observations, treatment, and use of PCR for stage determination of early stage of the disease.

Truc P, Lando A, Penchenier L, Vatunga G, Josenando T.

Source

Institut de Recherche pour le Développement, Unité Mixte de Recherche 177 IRD-CIRAD, Campus International de Baillarguet, TA A17/G, 34398, Montpellier Cedex 5, France.

Abstract

Biological and clinical observations are described for 224 patients infected by human African trypanosomiasis (HAT) in Angola in 2007 and 2008. Seven patients were initially classified in stage 1 (S1), 17 intermediate stage (IS) (WBC <20 lymphocytes/μl with absence of trypanosomes in cerebrospinal fluid (CSF) and no neurological signs), and 200 in stage 2 (S2). Out of 224 patients, 165 (73.6%) presented one or more neurological signs. During treatment with eflornithine, six deaths of S2 patients occurred, five of which were because of an encephalopathy syndrome. Nine patients were diagnosed with a relapse or suspected treatment failure during the follow-up: eight patients after treatment with eflornithine (relapse rate 4.1%) and one patient after pentamidine (6.6%). The contribution of PCR for stage determination evaluated for S1 and IS confirms the difficulty of stage determination, as one S1 patient and two IS patients were carriers of trypanosomes detected a posteriori by PCR in CSF but were treated with pentamidine while follow-up did not confirm treatment efficacy. Since 2001 in Angola, either by passive or active mode detection, approximately 80% of the new cases every year were in S2, whereas the annual number of cases has regressed, probably because the transmission of HAT is decreasing. However, stage determination and treatment remain two major issues for the chronic form of sleeping sickness.

Copyright © 2011 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

PMID:
22093811
[PubMed - as supplied by publisher]
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6. Biochim Biophys Acta. 2011 Nov 7. [Epub ahead of print]

Glycoconjugates in New World spec ies of Leishmania: Polymorphisms in lipophosphoglycan and glycoinositolphospholipids and interaction with hosts.

de Assis RR, Ibraim IC, Nogueira PM, Soares RP, Turco SJ.

Source

Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, FIOCRUZ, Av. Augusto de Lima, 1715, Belo Horizonte, MG 30190-002, Brazil.

Abstract

BACKGROUND:

Protozoan parasites of the genus Leishmania cause a number of important diseases in humans and undergo a complex life cycle, alternating between a sand fly vector and vertebrate hosts. The parasites have a remarkable capacity to avoid destruction in which surface molecules are determinant for survival. Among the many surface molecules of Leishmania, the glycoconjugates are known to play a central role in host/parasite interactions and are the focus of this review. SCOPE OF THE

REVIEW:

The most abundant and best studied glycoconjugates are the Lipophosphoglycans (LPGs) and glycoinositolphospholipids (GIPLs). This review summarizes the main studies on structure and biological functions of these molecules in New World Leishmania species.

MAJOR CONCLUSIONS:

LPG and GIPLs are complex molecules that display inter- and intraspecies polymorphisms. They are key elements for survival inside the vector and to modulate the vertebrate immune response during infection.

GENERAL SIGNIFICANCE:

Most of the studies on glycoconjugates focused on Old World Leishmania species. Here, it is reported some of the studies involving New World species and their biological significance on parasite/host interaction. This article is part of a Special Issue entitled Glycoproteomics.

Copyright © 2011. Published by Elsevier B.V.

PMID:
22093608
[PubMed - as supplied by publisher]
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7. BMC Evol Biol. 2011 Nov 17;11(1):334. [Epub ahead of print]

Evolu tionary and functional insights into Leishmania META1: evidence for lateral gene transfer and a role for META1 in secretion.

Puri V, Goyal A, Sankaranarayanan R, Enright AJ, Vaidya T.

Abstract

ABSTRACT:

BACKGROUND:

Leishmania META1 has for long been a candidate molecule for involvement in virulence: META1 transcript and protein are up-regulated in metacyclic Leishmania. Yet, how META1 contributes to virulence remains unclear. We sought insights into the possible functions of META1 by studying its evolutionary origins.

RESULTS:

Using multiple criteria including sequence similarity, nucleotide composition, phylogenetic analysis and selection pressure on gene sequence, we present evidence that META1 originated in trypanosomatids as a result of a lateral gene transfer of a bacterial heat-inducible protein, HslJ. Furthermore, within the Leishmania genome, META1 sequence is under negative selection pressure against change/substitution. Using homology modeling of Leishmania META1 based on solved NMR structure of HslJ, we show that META1 and HslJ share a similar structural fold. The best hit for other proteins with similar fold is MxiM, a protein involved in the type III secretion system in Shigella. The striking structural similarity shared by META1, HslJ and MxiM suggests a possibility of shared functions. Upon structural superposition with MxiM, we have observed a putative hydrophobic cavity in META1. Mutagenesis of select hydrophobic residues in this cavity affects the secretion of the secreted acid phosphatase (SAP), indicating META1's involvement in secretory processes in Leishmania.

CONCLUSIONS:

Overall, this work uses an evolutionary biology approach, 3D-modeling and site-directed mutagenesis to arrive at new insights into functions of Leishmania META1.

PMID:
22093578
[PubMed - as supplied by publisher]
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8. Parasit Vectors. 2011 Nov 17;4(1):217. [Epub ahead of print]

Multiple Trypanosoma infections are common amongst Glossina species in the new farming areas of Rufiji district, Tanzania.

Malele II, Magwisha HB, Nyingilili HS, Mamiro KA, Rukambile EJ, Daffa JW, Lyaruu EA, Kapange LA, Kasilagila GK, Lwitiko NK, Msami HM, Kimbita EN.

Abstract

ABSTRACT:

BACKGROUND:

Tsetse flies and trypanosomiasis are among several factors that constrain livestock development in Tanzania. Over the years Rufiji District was excluded from livestock production owing to tsetse fly infestation, however, a few years ago there was an influx of livestock following evictions aimed at conserving the Usangu wetlands.

METHODS:

A study was conducted to determine the efficiency of available traps for catching tsetse flies, Glossina species infesting the area, their infection rates and Trypanosoma species circulating in the area. Trapping was conducted during the semi dry season for a total of 30 days (ten days each month) during the onset of the dry season of May - July 2009. Harvested flies after every 24 hours were dissected and examined under a light microscope for trypanosome infections and whole fly DNA was extracted from 82 flies and analyzed for trypanosomes by polymerase chain reaction (PCR) using different sets of primers.

RESULTS:

The proportions of total tsetse catches per trap were in the following decreasing order S3 (33%), H-Trap (27%), Pyramidal (19%), sticky panel (11%) and biconical trap (10%). Of the 1200 trapped flies, 75.6% were identified as Glossina pallidipes, 11.7% as G. brevipalpis, 9.6% as G. austeni and 3.0% G. morsitans morsitans. Dissections revealed the overall infection rate of 6.6% (13/197). Whole DNA was extracted from 82 tsetse flies and the prevalence of trypanosomes circulating in the area in descending order was 92.7% (76/82) for T. simiae; 70.7% (58/82) for T. brucei types; 48.8% (40/82) for the T. vivax types and 32.9% (27/82) for the T. congolense types as determined by PCR. All trypanosome types were found in all tsetse species analysed except for the T. congolense types, which were absent in G. m. morsitans. None of the T. brucei positive samples contained human infective trypanosomes by SRA - PCR test

CONCLUSION:

All tsetse species found in Rufiji are biologically important in the transmission of animal trypanosomiasis and the absence of T. congolense in G. m. morsitans could be a matter of chance only. Therefore, plans for control should consider all tsetse species.

PMID:
22093363
[PubMed - as supplied by publisher]
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9. J Eur Acad Dermatol Venereol. 2011 Nov 18. doi: 10.1111/j.1468-3083.2011.04339.x. [Epub ahead of print]

Public awareness and attitudes towards cutaneous leishmaniasis in an endemic region in Saudi Arabia.

Amin TT, Kaliyadan F, Al-Ajyan MI, Al-Arfaj AK, Al-Mujhim MA, Al-Harbi SJ, Al Mohammed HI.

Source

Community Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt Family and Community Medicine, College of Medicine, King Faisal University, Hofuf, Saudi Arabia Internal Medicine Department, Dermatology Division, College of Medicine, King Faisal University, Hofuf, Saudi Arabia Ministry of Health, Local Health Directorate, Hofuf, Saudi Arabia National Guard Corporation, Health Sector, Hofuf, Saudi Arabia Parasitology Division, Department of Biomedical Sciences, College of Medicine, King Faisal University, Hofuf, Saudi Arabia.

Abstract

Background and Aims  One of the priorities in public health policy for the control of Cutaneous Leishmaniasis (CL) is to investigate associations between disease distribution, socio-demographical and environmental risk factors, so that rational prevention and control strategies can be developed. Assessment of baseline awareness of the disease amongst the endemic population would be one of the first steps in this direction. This study aims to provide qualitative information on lay perceptions of CL in an endemic area in Saudi Arabia. We also attempted to correlate these perceptions with associated socio-demographical backgrounds. Methods  This was a cross-sectional descriptive survey carried out in Al-Hassa, located in the Eastern Province of Saudi Arabia. The study included 1824 participants, age ranging from 15 to 63 years (mean 35.86 ± 9.54 years). Results  Over 76% of the studied population recognized the infectious nature of CL. There was also good awareness regarding the clinical features of CL, but the awareness regarding the vector, transmission, risk factors and preventive methods were very poor. Our study demonstrated a significantly higher knowledge score correlated with regard to male gender, higher family income, age and a previous history of CL. Conclusion  In our study we found low awareness for important epidemiological aspects like transmission of the disease, risk factors and prevention. Our study provides a baseline to understand and correct deficits in the perceptions and knowledge regarding CL in Saudi Arabia and would provide a template to design interventions.

© 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.

PMID:
22092482
[PubMed - as supplied by publisher]
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