Publications by authors named "Dhafer Laouini"

44 Publications

Identification and characterization of multidrug-resistant ESBL-producing Salmonella enterica serovars Kentucky and Typhimurium isolated in Tunisia CTX-M-61/TEM-34, a novel cefotaxime-hydrolyzing β-lactamase of Salmonella.

J Appl Microbiol 2021 Jul 12. Epub 2021 Jul 12.

Water and Food Control Lab, National Center of Salmonella, Shigella, Vibrio-Enteropathogens - Institut Pasteur de Tunis (IPT) Tunis-Belvédère, Tunis, Tunisia.

Aims: Molecular characterization of extended-spectrum β-lactamases (ESBLs) among Salmonella Kentucky and Typhimurium isolates: partial sequence analysis of the types of β-lactamases found in these isolates, clonality, resistance and supposed emergence of ESBL-producing strains.

Methods And Results: A retrospective study surveyed the ESBLs occurring in a total of 1404 Salmonella Kentucky and Typhimurium isolates collected over a five-year period in Tunisia. Antimicrobial susceptibility tests, ESBL phenotype determination (double-disc synergy) were performed. Polymerase chain reaction assays were used for the detection of β-lactamase genes (bla , bla , bla and bla ), class 1 and class 2 integrases (intI1 and intI2) and the 3' conserved segment (3'-CS) of class 1 integron (qacEΔ1+sul1). Sequencing of amplicons of β-lactamase genes was performed. Percentage of 9.8 of the isolates (S. Kentucky=117, S. Typhimurium= 20) were either resistant to penicillin and had decreased susceptibility to cefotaxime or had a positive double-disc synergy test result. PCR detected that these isolates harboured one or more β-lactamase genes (bla , bla , bla or bla ). TEM-1, TEM-34, CTX-M15, CTX-M9 and CTX-M61 type ESBLs were identified through sequencing. The novel Salmonella cefotaxime-hydrolyzing β-lactamase, CTX-M61/TEM-34, detected in this study showed the emergence of new CTX-M-type ESBLs in Tunisia. There were found 33 different multidrug resistance patterns.

Conclusion: These findings highlighted the proliferation of ESBLs and multidrug resistance in Salmonella Kentucky and Typhimurium isolates from numerous regions and sources in Tunisia, indicating an emerging public health concern.

Significance And Impact Of Study: For the first time CTX-M-61/TEM-34, a novel cefotaxime-hydrolyzing β-lactamase of Salmonella had been detected.
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http://dx.doi.org/10.1111/jam.15211DOI Listing
July 2021

Magnetic Separation and Centri-Chronoamperometric Detection of Foodborne Bacteria Using Antibiotic-Coated Metallic Nanoparticles.

Biosensors (Basel) 2021 Jun 23;11(7). Epub 2021 Jun 23.

Faculté des Sciences de Tunis, Campus Universitaire, El Manar, Tunis 2092, Tunisia.

Quality and food safety represent a major stake and growing societal challenge in the world. Bacterial contamination of food and water resources is an element that pushes scientists to develop new means for the rapid and efficient detection and identification of these pathogens. Conventional detection tools are often bulky, laborious, expensive to buy, and, above all, require an analysis time of a few hours to several days. The interest in developing new, simple, rapid, and nonlaborious bacteriological diagnostic methods is therefore increasingly important for scientists, industry, and regulatory bodies. In this study, antibiotic-functionalized metallic nanoparticles were used to isolate and identify the foodborne bacterial strains and . With this aim, a new diagnostic tool for the rapid detection of foodborne pathogenic bacteria, gold nanoparticle-based centri-chronoamperometry, has been developed. Vancomycin was first stabilized at the surface of gold nanoparticles and then incubated with the bacteria or to form the [email protected]/bacteria complex. This complex was separated by centrifugation, then treated with hydrochloric acid and placed at the surface of a carbon microelectrode. The gold nanoparticles of the formed complex catalyzed the hydrogen reduction reaction, and the generated current was used as an analytical signal. Our results show the possibility of the simple and rapid detection of the and strains at very low numbers of 3 cells/mL and 12 cells/mL, respectively. On the other hand, vancomycin-capped magnetic beads were easily synthesized and then used to separate the bacteria from the culture medium. The results show that vancomycin at the surface of these metallic nanoparticles is able to interact with the bacteria membrane and then used to separate the bacteria and to purify an inoculated medium.
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http://dx.doi.org/10.3390/bios11070205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301846PMC
June 2021

A prospective cohort study of Cutaneous Leishmaniasis due to Leishmania major: Dynamics of the Leishmanin skin test and its predictive value for protection against infection and disease.

PLoS Negl Trop Dis 2020 08 25;14(8):e0008550. Epub 2020 Aug 25.

Department of Medical Epidemiology, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia.

Background: Leishmanin Skin Test (LST) is considered as a useful indicator of past infection by Leishmania parasites. However, the temporal dynamics of a positive LST under different epidemiologic scenarios and whether it relates to the protection against the recurrence of an overt disease are not fully documented.

Methodology/principal Findings: We report here on a population based prospective study conducted on 2686 individuals living in two foci located in Central Tunisia, to assess over a one-year epidemiologic season, the incidence of Leishmania (L.) major infection and disease and changes in LST reactivity. The two foci were both endemic for Cutaneous Leishmaniasis (CL) due to L. major, but contrasted in their history for this disease (ie: an old focus versus a recent focus). We found that most infections occurred in the new focus (290/1000; 95% CI: 265-315 person-years) with an incidence rate of CL lesions 2.4 times higher than in the old focus. Likewise, the rates of LST reactivity reversion and loss, in the new focus, were 99/1000[38-116] person-years and 14/1000[8-21] person-years, respectively. Loss of LST reactivity was not noticed in the old focus. Interestingly, the incidence rates of symptomatic infection did not differ significantly according to the LST status at enrolment (negative versus positive) between the combined foci and the new one.

Conclusions/significance: Our findings confirm LST as a good tool for assessing L. major cryptic infection. However, the instability of the LST positivity in new foci should be considered as an important confounder of the outcome of this infection when developing a research protocol for vaccine trial.
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http://dx.doi.org/10.1371/journal.pntd.0008550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473511PMC
August 2020

Casein-Conjugated Gold Nanoparticles for Amperometric Detection of .

Biosensors (Basel) 2019 May 27;9(2). Epub 2019 May 27.

Université Tunis El Manar, Tunis 1068, Tunisia.

Sensitive and reliable approaches targeting the detection of are critical for effective early diagnosis and treatment of leishmaniasis. In this frame, this paper describes a rapid quantification assay to detect parasites based on the combination of the electrocatalytic ability of gold nanoparticles (AuNPs) to act as a catalyst for the hydrogen formation reaction along with the specificity of the interaction between casein and the major surface protease of the parasite, GP63. First, pure and casein-modified AuNPs were prepared and characterized by scanning electron microscopy and ultraviolet-visible spectroscopy. Then, casein-conjugated AuNPs were incubated with parasites in solution; the formed complex was collected by centrifugation, treated by acidic solution, and the pelleted AuNPs were placed on screen-printed carbon electrodes (SPCEs) and chronoamperometric measurements were carried out. Our results suggest that it is possible to detect parasites, with a limit less than 1 parasite/mL. A linear response over a wide concentration interval, ranging from 2 × 10 to 2 × 10 parasites/mL, was achieved. Additionally, a pretreatment of parasites with Amphotericin B, diminished their interaction with casein. This findings and methodology are very useful for drug efficacy assessment.
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http://dx.doi.org/10.3390/bios9020068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627895PMC
May 2019

Designing and running an advanced Bioinformatics and genome analyses course in Tunisia.

PLoS Comput Biol 2019 01 28;15(1):e1006373. Epub 2019 Jan 28.

Institut Pasteur Paris, 28 rue du Dr Roux, 75724 Paris cedex 15, France.

Genome data, with underlying new knowledge, are accumulating at exponential rate thanks to ever-improving sequencing technologies and the parallel development of dedicated efficient Bioinformatics methods and tools. Advanced Education in Bioinformatics and Genome Analyses is to a large extent not accessible to students in developing countries where endeavors to set up Bioinformatics courses concern most often only basic levels. Here, we report a pioneering pilot experience concerning the design and implementation, from scratch, of a three-months advanced and extensive course in Bioinformatics and Genome Analyses in the Institut Pasteur de Tunis. Most significantly the outcome of the course was upgrading the participants' skills in Bioinformatics and Genome Analyses to recognized international standards. Here we detail the different steps involved in the implementation of this course as well as the topics covered in the program. The description of this pilot experience might be helpful for the implementation of other similar educational projects, notably in developing countries, aiming to go beyond basics and providing young researchers with high-level skills.
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http://dx.doi.org/10.1371/journal.pcbi.1006373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349305PMC
January 2019

Ligand-Capped Ultrapure Metal Nanoparticle Sensors for the Detection of Cutaneous Leishmaniasis Disease in Exhaled Breath.

ACS Sens 2018 12 16;3(12):2532-2540. Epub 2018 Nov 16.

MINOS-EMaS, Department of Electronics, Electrical and Automatic Engineering , Rovira i Virgili University , Tarragona 43007 , Spain.

Human cutaneous leishmaniasis, although designated as one of the most neglected tropical diseases, remains underestimated due to its misdiagnosis. The diagnosis is mainly based on the microscopic detection of amastigote forms, isolation of the parasite, or the detection of Leishmania DNA, in addition to its differential clinical characterization; these tools are not always available in routine daily practice, and they are expensive and time-consuming. Here, we present a simple-to-use, noninvasive approach for human cutaneous leishmaniasis diagnosis, which is based on the analysis of volatile organic compounds in exhaled breath with an array of specifically designed chemical gas sensors. The study was realized on a group of n = 28 volunteers diagnosed with human cutaneous leishmaniasis and a group of n = 32 healthy controls, recruited in various sites from Tunisia, an endemic country of the disease. The classification success rate of human cutaneous leishmaniasis patients achieved by our sensors test was 98.2% accuracy, 96.4% sensitivity, and 100% specificity. Remarkably, one of the sensors, based on CuNPs functionalized with 2-mercaptobenzoxazole, yielded 100% accuracy, 100% sensitivity, and 100% specificity for human cutaneous leishmaniasis discrimination. While AuNPs have been the most extensively used in metal nanoparticle-ligand sensing films for breath sensing, our results demonstrate that chemical sensors based on ligand-capped CuNPs also hold great potential for breath volatile organic compounds detection. Additionally, the chemical analysis of the breath samples with gas chromatography coupled to mass spectrometry identified nine putative breath biomarkers for human cutaneous leishmaniasis.
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http://dx.doi.org/10.1021/acssensors.8b00759DOI Listing
December 2018

Genome Dynamics during Environmental Adaptation Reveal Strain-Specific Differences in Gene Copy Number Variation, Karyotype Instability, and Telomeric Amplification.

mBio 2018 11 6;9(6). Epub 2018 Nov 6.

Unité de Parasitologiemoléculaire et Signalisation, Institut Pasteur, Paris, France

Protozoan parasites of the genus adapt to environmental change through chromosome and gene copy number variations. Only little is known about external or intrinsic factors that govern genomic adaptation. Here, by conducting longitudinal genome analyses of 10 new clinical isolates, we uncovered important differences in gene copy number among genetically highly related strains and revealed gain and loss of gene copies as potential drivers of long-term environmental adaptation in the field. In contrast, chromosome rather than gene amplification was associated with short-term environmental adaptation to culture. Karyotypic solutions were highly reproducible but unique for a given strain, suggesting that chromosome amplification is under positive selection and dependent on species- and strain-specific intrinsic factors. We revealed a progressive increase in read depth towards the chromosome ends for various isolates, which may represent a nonclassical mechanism of telomere maintenance that can preserve integrity of chromosome ends during selection for fast growth. Together our data draw a complex picture of genomic adaptation in the field and in culture, which is driven by a combination of intrinsic genetic factors that generate strain-specific phenotypic variations, which are under environmental selection and allow for fitness gain. Protozoan parasites of the genus cause severe human and veterinary diseases worldwide, termed leishmaniases. A hallmark of biology is its capacity to adapt to a variety of unpredictable fluctuations inside its human host, notably pharmacological interventions, thus, causing drug resistance. Here we investigated mechanisms of environmental adaptation using a comparative genomics approach by sequencing 10 new clinical isolates of the , , and complexes that were sampled across eight distinct geographical regions. Our data provide new evidence that parasites adapt to environmental change in the field and in culture through a combination of chromosome and gene amplification that likely causes phenotypic variation and drives parasite fitness gains in response to environmental constraints. This novel form of gene expression regulation through genomic change compensates for the absence of classical transcriptional control in these early-branching eukaryotes and opens new venues for biomarker discovery.
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http://dx.doi.org/10.1128/mBio.01399-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222132PMC
November 2018

Diagnosis of Human Echinococcosis via Exhaled Breath Analysis: A Promise for Rapid Diagnosis of Infectious Diseases Caused by Helminths.

J Infect Dis 2019 01;219(1):101-109

Department of Electronics, Electrical and Automatic Engineering, Rovira i Virgili University, Tarragona, Spain.

Background: Human echinococcosis is a neglected infectious disease affecting more than 1 million people globally. Its diagnosis is expensive and difficult because of lack of adequate resources in low-resource locations, where most cases occur.

Methods: A group of volunteers diagnosed with the 2 main types of echinococcosis and corresponding control groups were recruited from hospitals in Tunisia (32 patients with cystic echinococcosis and 43 controls) and Poland (16 patients with alveolar echinococcosis and 8 controls). Breath samples were collected from all patients and analyzed by gas chromatography coupled to mass spectrometry, and a specifically developed electronic nose system.

Results: The chemical analysis revealed statistically different concentrations of 2 compounds in the breath of patients with cystic echinococcosis compared to controls, and statistically different concentrations of 7 compounds in the breath of patients with alveolar echinococcosis compared to controls. The discrimination accuracy achieved by the electronic nose system was 100% for cystic echinococcosis and 92.9% for alveolar echinococcosis, while the discrimination accuracy between these 2 patient groups was 92.1%.

Conclusion: Here we advocate a noninvasive, fast, easy-to-operate and nonexpensive diagnostic tool for the diagnosis of human echinococcosis disease through exhaled breath analysis, suitable for early diagnosis and population screening.
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http://dx.doi.org/10.1093/infdis/jiy449DOI Listing
January 2019

Role of Human Macrophage Polarization in Inflammation during Infectious Diseases.

Int J Mol Sci 2018 06 19;19(6). Epub 2018 Jun 19.

Institut Pasteur de Tunis, LR11IPT02, Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Tunis-Belvédère 1002, Tunisia.

Experimental models have often been at the origin of immunological paradigms such as the M1/M2 dichotomy following macrophage polarization. However, this clear dichotomy in animal models is not as obvious in humans, and the separating line between M1-like and M2-like macrophages is rather represented by a continuum, where boundaries are still unclear. Indeed, human infectious diseases, are characterized by either a back and forth or often a mixed profile between the pro-inflammatory microenvironment (dominated by interleukin (IL)-1β, IL-6, IL-12, IL-23 and Tumor Necrosis Factor (TNF)-α cytokines) and tissue injury driven by classically activated macrophages (M1-like) and wound healing driven by alternatively activated macrophages (M2-like) in an anti-inflammatory environment (dominated by IL-10, Transforming growth factor (TGF)-β, chemokine ligand (CCL)1, CCL2, CCL17, CCL18, and CCL22). This review brews the complexity of the situation during infectious diseases by stressing on this continuum between M1-like and M2-like extremes. We first discuss the basic biology of macrophage polarization, function, and role in the inflammatory process and its resolution. Secondly, we discuss the relevance of the macrophage polarization continuum during infectious and neglected diseases, and the possibility to interfere with such activation states as a promising therapeutic strategy in the treatment of such diseases.
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http://dx.doi.org/10.3390/ijms19061801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032107PMC
June 2018

Electrochemical detection of influenza virus H9N2 based on both immunomagnetic extraction and gold catalysis using an immobilization-free screen printed carbon microelectrode.

Biosens Bioelectron 2018 Jun 7;107:170-177. Epub 2018 Feb 7.

Institut Pasteur de Tunis, LR11IPT03, Laboratory of Epidemiology and Veterinary Microbiology (LEMV), Tunis-Belvédère 1002, Tunisia; Université Tunis El Manar, Tunis 1068, Tunisia. Electronic address:

Influenza is a viral infectious disease considered as a source of many health problems and enormous socioeconomic disruptions. Conventional methods are inadequate for in-field detection of the virus and generally suffer from being laborious and time-consuming. Thus, studies aiming to develop effective alternatives to conventional methods are urgently needed. In this work, we developed an approach for the isolation and detection of influenza A virus subtype H9N2. For this aim, two specific influenza receptors were used. The first, anti-matrix protein 2 (M2) antibody, was attached to iron magnetic nanoparticles (MNPs) and used for the isolation of the virus from allantoic fluid. The second biomolecule, Fetuin A, was attached to an electrochemical detectable label, gold nanoparticles (AuNPs), and used to detect the virus tacking advantage from fetuin-hemagglutinin interaction. The MNP-Influenza virus-AuNP formed complex was isolated and treated by an acid solution then the collected gold nanoparticles were deposited onto a screen printed carbon electrode. AuNPs catalyzes the hydrogen ions reduction in acidic medium while applying an appropriate potential, and the generated current signal was proportional to the virus titer. This approach allows the rapid detection of influenza virus A/H9N2 at a less than 16 HAU titer.
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http://dx.doi.org/10.1016/j.bios.2018.02.018DOI Listing
June 2018

Secretory lipase from the human pathogen Leishmania major: Heterologous expression in the yeast Pichia pastoris and biochemical characterization.

Biochimie 2018 Mar 13;146:119-126. Epub 2017 Dec 13.

Laboratoire de Biochimie et de Génie Enzymatique des Lipases, Université de Sfax, ENIS Route de Soukra, Sfax, Tunisia. Electronic address:

Leishmaniasis is a parasitic reticuloendotheliosis whose pathogen is a zooflagellate belonging to the genus Leishmania transmitted by the bite of an infected phlebotome. Recently, a unique secretory lipase from the human pathogen Leishmania donovani Ldlip3 has been identified and characterized. This lipase has a high identity with a putative triacylglycerol lipase of Leishmania major (Lmlip2). In the present study, Lmlip2 was expressed in the eukaryotic heterologous expression system Pichia pastoris as tagged enzyme of 308 amino acids. Maximal protein production was reached after 2 days of fermentation. Optimal Lmlip2 lipase activity was measured using the pH stat technique at pH 8 at 26 °C using vinyl esters and triacylglycerols (true lipids) as substrates. Moreover, biochemical characterization of Lmlip2 contained in culture supernatant, illustrates that L. major secreted lipase is active and stable at low temperatures especially 26°and prefer neutral pH; concerning substrate specificityLmlip2 presents a preference for short chains lipid substrates vinyl esters such as VC2, VC3 and VC4 likewise, it is capable to hydrolyze long chain triacylglycerols like olive oil. Metal ions and surfactants tested in this study decrease Lmlip2 activity. Further studies are needed to clarify the relation between the lipase activity and the virulence. Thus, it could lead to the identification of novel targets to block cutaneous Leishmaniasis in human hosts.
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http://dx.doi.org/10.1016/j.biochi.2017.12.002DOI Listing
March 2018

Insight into the global evolution of Rodentia associated Morbilli-related paramyxoviruses.

Sci Rep 2017 05 16;7(1):1974. Epub 2017 May 16.

Centre de Recherche et de Veille sur les maladies émergentes dans l'Océan Indien (CRVOI), Plateforme de Recherche CYROI, Sainte Clotilde, La Réunion, France.

One portion of the family Paramyxoviridae is a group of Unclassified Morbilli-Related Viruses (UMRV) recently recognized in wild small mammals. At a global level, the evolutionary history of these viruses is not properly understood and the relationships between UMRV and their hosts still remain largely unstudied. The present study revealed, for the first time, that Rodentia associated UMRV emerged from a common ancestor in southern Africa more than 4000 years ago. Sequenced UMRV originating from different regions in the world, clustered into four well-supported viral lineages, which suggest that strain diversification occurred during host dispersal and associated exchanges, with purifying selection pressure as the principal evolutionary force. In addition, multi-introductions on different continents and islands of Rodentia associated UMRV and spillover between rodent species, most probably Rattus rattus, were detected and indicate that these animals are implicated in the vectoring and in the worldwide emergence of this virus group. The natural history and the evolution dynamics of these zoonotic viruses, originating from and hosted by wild animals, are most likely shaped by commensalism related to human activities.
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http://dx.doi.org/10.1038/s41598-017-02206-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5434063PMC
May 2017

Detection of ESAT-6 by a label free miniature immuno-electrochemical biosensor as a diagnostic tool for tuberculosis.

Mater Sci Eng C Mater Biol Appl 2017 May 13;74:465-470. Epub 2016 Dec 13.

Institut Pasteur de Tunis, LR11IPT02, Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Tunis-Belvédère 1002, Tunisia; Université Tunis El Manar, Tunis 1068, Tunisia.

Tuberculosis is a worldwide disease considered as a major health problem with high morbidity and mortality rates. Poor detection of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis remains a major obstacle to the global control of this disease. Here we report the development of a new test based on the detection of the major virulent factor of Mtb, namely the early secreted antigenic target 6-kDa protein or ESAT-6. A label free electrochemical immunosensor using an anti-ESAT-6 monoclonal antibody as a bio-receptor is described herein. Anti-ESAT-6 antibodies were first covalently immobilized on the surface of a gold screen-printed electrode functionalized via a self-assembled thiol monolayer. Interaction between the bio-receptor and ESAT-6 antigen was evaluated by square wave voltammetry method using [F(CN)] as redox probe. The detection limit of ESAT-6 antigen was 7ng/ml. The immunosensor has also been able to detect native ESAT-6 antigen secreted in cell culture filtrates of three pathogenic strains of Mtb (CDC1551, H37RV and H8N8). Overall, this work describes an immune-electrochemical biosensor, based on ESAT-6 antigen detection, as a useful diagnostic tool for tuberculosis.
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http://dx.doi.org/10.1016/j.msec.2016.12.051DOI Listing
May 2017

Letter to the Editor: Hypoxia inducible factor 1α: A critical factor for the immune response to pathogens and Leishmania.

Cell Immunol 2016 12;310:211

Institut Pasteur de Tunis, LR11IPT02, Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Tunis-Belvédère 1002, Tunisia; Université Tunis El Manar, Tunis 1068, Tunisia. Electronic address:

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http://dx.doi.org/10.1016/j.cellimm.2016.08.009DOI Listing
December 2016

Evaluation of anti-proliferative and anti-inflammatory activities of Pelagia noctiluca venom in Lipopolysaccharide/Interferon-γ stimulated RAW264.7 macrophages.

Biomed Pharmacother 2016 Dec 18;84:1986-1991. Epub 2016 Nov 18.

Faculty of Dental Medicine of Monastir, Laboratory for Research on Biologically Compatible Compounds, Rue Avicenne, 5019 Monastir, Tunisia; University of Jendouba, AlFaeiz, Street Jamil Boutheina Jendouba 8100, Tunisia.

Components of Pelagia noctiluca (P. noctiluca) venom were evaluated for their anticancer and nitric Oxide (NO) inhibition activities. Three fractions, out of four, obtained by gel filtration on Sephadex G75 of P. noctiluca venom revealed an important selective anti-proliferative activity on several cell lines such as human bladder carcinoma (RT112), human glioblastoma (U87), and human myelogenous leukemia (K562) but not on mitogen-stimulated peripheral blood mononuclear cells. Interestingly, P. noctiluca components showed an important dose-dependent anti-inflammatory activity, through inhibition of NO production via transcriptional regulation of Inducible NO Synthase (iNOS), in IFN-γ/LPS stimulated RAW 264.7 macrophages. These data strongly suggest that P. noctiluca venom could be used as a natural inhibitor of cancer cell lines and a potent anti-inflammatory agent for the treatment of anti-inflammatory diseases.
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http://dx.doi.org/10.1016/j.biopha.2016.11.010DOI Listing
December 2016

Comparative genomics of Tunisian Leishmania major isolates causing human cutaneous leishmaniasis with contrasting clinical severity.

Infect Genet Evol 2017 06 4;50:110-120. Epub 2016 Nov 4.

Institut Pasteur de Tunis, LR11IPT02, Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Tunis, Belvédère, 1002, Tunisia; Université Tunis El Manar, Tunis 1068, Tunisia.

Zoonotic cutaneous leishmaniasis caused by Leishmania (L.) major parasites affects urban and suburban areas in the center and south of Tunisia where the disease is endemo-epidemic. Several cases were reported in human patients for which infection due to L. major induced lesions with a broad range of severity. However, very little is known about the mechanisms underlying this diversity. Our hypothesis is that parasite genomic variability could, in addition to the host immunological background, contribute to the intra-species clinical variability observed in patients and explain the lesion size differences observed in the experimental model. Based on several epidemiological, in vivo and in vitro experiments, we focused on two clinical isolates showing contrasted severity in patients and BALB/c experimental mice model. We used DNA-seq as a high-throughput technology to facilitate the identification of genetic variants with discriminating potential between both isolates. Our results demonstrate that various levels of heterogeneity could be found between both L. major isolates in terms of chromosome or gene copy number variation (CNV), and that the intra-species divergence could surprisingly be related to single nucleotide polymorphisms (SNPs) and Insertion/Deletion (InDels) events. Interestingly, we particularly focused here on genes affected by both types of variants and correlated them with the observed gene CNV. Whether these differences are sufficient to explain the severity in patients is obviously still open to debate, but we do believe that additional layers of -omic information is needed to complement the genomic screen in order to draw a more complete map of severity determinants.
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http://dx.doi.org/10.1016/j.meegid.2016.10.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376240PMC
June 2017

Treatment with synthetic lipophilic tyrosyl ester controls Leishmania major infection by reducing parasite load in BALB/c mice.

Parasitology 2016 10 17;143(12):1615-21. Epub 2016 Jun 17.

Laboratory of Transmission, Control and Immunobiology of Infections (LTCII),Institut Pasteur de Tunis,LR11IPT02, Tunis-Belvédère, 1002,Tunisia.

Synthesized lipophilic tyrosyl ester derivatives with increasing lipophilicity were effective against Leishmania (L.) major and Leishmania infantum species in vitro. These findings prompted us to test in vivo leishmanicidal properties of these molecules and their potential effect on the modulation of immune responses. The experimental BALB/c model of cutaneous leishmaniasis was used in this study. Mice were infected with L. major parasites and treated with three in vitro active tyrosyl esters derivatives. Among these tested tyrosylcaprate (TyC) compounds, only TyC10 exhibited an in vivo anti-leishmanial activity, when injected sub-cutaneously (s.c.). TyC10 treatment of L. major-infected BALB/c mice resulted in a decrease of lesion development and parasite load. TyC10 s.c. treatment of non-infected mice induced an imbalance in interferon γ/interleukin 4 (IFN-γ/IL-4) ratio cytokines towards a Th1 response. Our results indicate that TyC10 s.c. treatment improves lesions' healing and parasite clearance and may act on the cytokine balance towards a Th1 protective response by decreasing IL-4 and increasing IFN-γ transcripts. TyC10 is worthy of further investigation to uncover its mechanism of action that could lead to consider this molecule as a potential drug candidate.
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http://dx.doi.org/10.1017/S0031182016001086DOI Listing
October 2016

Genetic micro-heterogeneity of Leishmania major in emerging foci of zoonotic cutaneous leishmaniasis in Tunisia.

Infect Genet Evol 2016 09 30;43:179-85. Epub 2016 Apr 30.

Institut Pasteur de Tunis, LR11IPT02, Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Tunis-Belvédère 1002, Tunisia; Université Tunis El Manar, Tunis 1068, Tunisia. Electronic address:

Tunisia is endemic for zoonotic cutaneous leishmaniasis (ZCL), a parasitic disease caused by Leishmania (L.) major. ZCL displays a wide clinical polymorphism, with severe forms present more frequently in emerging foci where naive populations are dominant. In this study, we applied the multi-locus microsatellite typing (MLMT) using ten highly informative and discriminative markers to investigate the genetic structure of 35 Tunisian Leishmania (L.) major isolates collected from patients living in five different foci of Central Tunisia (two old and three emerging foci). Phylogenetic reconstructions based on genetic distances showed that nine of the ten tested loci were homogeneous in all isolates with homozygous alleles, whereas one locus (71AT) had a 58/64-bp bi-allelic profile with an allele linked to emerging foci. Promastigote-stage parasites with the 58-bp allele tend to be more resistant to in vitro complement lysis. These results, which stress the geographical dependence of the genetic micro-heterogeneity, may improve our understanding of the ZCL epidemiology and clinical outcome.
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http://dx.doi.org/10.1016/j.meegid.2016.04.032DOI Listing
September 2016

Current approaches and challenges for chemical characterization of inhibitory effect against cancer cell line isolated from Gokshur extract.

J Chromatogr B Analyt Technol Biomed Life Sci 2016 Jul 27;1026:279-285. Epub 2015 Nov 27.

Environmental Biomonitoring Laboratory LBE (LR01/ES14), Faculty of Sciences of Bizerta, University of Carthage, Tunisia.

In the present study, the potential effect anti tumor and the chemical composition of different fractions of Gokshur was evaluated. Commonly known as puncture vine, it has been used for a long time in both the Indian and traditional Chinese medicine. It is popularly used as a remedy for fertility disorder in Ayurveda. Samples were collected during June-September 2014 in the Cap Bon (north east of the northern Tunisia). Different organs were separated and extracted by sequential process to compare and investigate their potential anti-tumor effect. For the first time, we report the antiproliferatif effect of leaves n-butannolic fraction against cancer cell lines. The better anti-tumor fraction (94.76±1.52%) has been detected and performed by RP-HPLC has shown a great peak area (5578.21Mau). Novel designed natural derivatives from Gokshur, a cyclotrisiloxane, major compound identified by GC-MS.
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http://dx.doi.org/10.1016/j.jchromb.2015.11.023DOI Listing
July 2016

Genotype profile of Leishmania major strains isolated from tunisian rodent reservoir hosts revealed by multilocus microsatellite typing.

PLoS One 2014 9;9(9):e107043. Epub 2014 Sep 9.

Institut Pasteur de Tunis, Service of Medical Epidemiology, Tunis-Belvédère, Tunisia; Institut Pasteur de Tunis, LR11IPT02, Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Tunis-Belvédère, Tunisia; Université Tunis El Manar, Tunis, Tunisia.

Zoonotic cutaneous leishmaniasis (ZCL) caused by Leishmania (L.) major parasites represents a major health problem with a large spectrum of clinical manifestations. Psammomys (P.) obesus and Meriones (M.) shawi represent the most important host reservoirs of these parasites in Tunisia. We already reported that infection prevalence is different between these two rodent species. We aimed in this work to evaluate the importance of genetic diversity in L. major parasites isolated from different proven and suspected reservoirs for ZCL. Using the multilocus microsatellites typing (MLMT), we analyzed the genetic diversity among strains isolated from (i) P. obesus (n = 31), (ii) M. shawi (n = 8) and (iii) Mustela nivalis (n = 1), captured in Sidi Bouzid, an endemic region for ZCL located in the Center of Tunisia. Studied strains present a new homogeneous genotype profile so far as all tested markers and showed no polymorphism regardless of the parasite host-reservoir origin. This lack of genetic diversity among these L. major isolates is the first genetic information on strains isolated from Leishmania reservoirs hosts in Tunisia. This result indicates that rodent hosts are unlikely to exert a selective pressure on parasites and stresses on the similarity of geographic and ecological features in this study area. Overall, these results increase our knowledge among rodent reservoir hosts and L. major parasites interaction.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0107043PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159323PMC
May 2015

Lipophilization of ascorbic acid: a monolayer study and biological and antileishmanial activities.

J Agric Food Chem 2014 Sep 3;62(37):9118-27. Epub 2014 Sep 3.

Laboratoire de Biochimie et de Génie Enzymatique des Lipases, ENIS, Université de Sfax , Route de Soukra, BPW 1173, 3038 Sfax, Tunisia.

Ascorbyl lipophilic derivatives (Asc-C2 to Asc-C(18:1)) were synthesized in a good yield using lipase from Staphylococcus xylosus produced in our laboratory and immobilized onto silica aerogel. Results showed that esterification had little effect on radical-scavenging capacity of purified ascorbyl esters using DPPH assay in ethanol. However, long chain fatty acid esters displayed higher protection of target lipids from oxidation. Moreover, compared to ascorbic acid, synthesized derivatives exhibited an antibacterial effect. Furthermore, ascorbyl derivatives were evaluated, for the first time, for their antileishmanial effects against visceral (Leishmania infantum) and cutaneous parasites (Leishmania major). Among all the tested compounds, only Asc-C10, Asc-C12, and Asc-C(18:1) exhibited antileishmanial activities. The interaction of ascorbyl esters with a phospholipid monolayer showed that only medium and unsaturated long chain (Asc-C10 to Asc-C(18:1)) derivative esters were found to interact efficiently with mimetic membrane of leishmania. These properties would make ascorbyl derivatives good candidates to be used in cosmetic and pharmaceutical lipophilic formulations.
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http://dx.doi.org/10.1021/jf5029398DOI Listing
September 2014

Identification of divergent protein domains by combining HMM-HMM comparisons and co-occurrence detection.

PLoS One 2014 5;9(6):e95275. Epub 2014 Jun 5.

Institut de Biologie Computationnelle, LIRMM, CNRS, Univ. Montpellier 2, Montpellier, France.

Identification of protein domains is a key step for understanding protein function. Hidden Markov Models (HMMs) have proved to be a powerful tool for this task. The Pfam database notably provides a large collection of HMMs which are widely used for the annotation of proteins in sequenced organisms. This is done via sequence/HMM comparisons. However, this approach may lack sensitivity when searching for domains in divergent species. Recently, methods for HMM/HMM comparisons have been proposed and proved to be more sensitive than sequence/HMM approaches in certain cases. However, these approaches are usually not used for protein domain discovery at a genome scale, and the benefit that could be expected from their utilization for this problem has not been investigated. Using proteins of P. falciparum and L. major as examples, we investigate the extent to which HMM/HMM comparisons can identify new domain occurrences not already identified by sequence/HMM approaches. We show that although HMM/HMM comparisons are much more sensitive than sequence/HMM comparisons, they are not sufficiently accurate to be used as a standalone complement of sequence/HMM approaches at the genome scale. Hence, we propose to use domain co-occurrence--the general domain tendency to preferentially appear along with some favorite domains in the proteins--to improve the accuracy of the approach. We show that the combination of HMM/HMM comparisons and co-occurrence domain detection boosts protein annotations. At an estimated False Discovery Rate of 5%, it revealed 901 and 1098 new domains in Plasmodium and Leishmania proteins, respectively. Manual inspection of part of these predictions shows that it contains several domain families that were missing in the two organisms. All new domain occurrences have been integrated in the EuPathDomains database, along with the GO annotations that can be deduced.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0095275PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046975PMC
August 2015

[Leishmania epidemiology, diagnosis, chemotherapy and vaccination approaches in the international network of Pasteur Institutes].

Med Sci (Paris) 2013 Dec 20;29(12):1151-60. Epub 2013 Dec 20.

Laboratoire de parasitologie-mycologie, LR 11-IPT-06 parasitoses médicales, biotechnologie et biomolécules, Institut Pasteur de Tunis, 13, place Pasteur, BP 74, 1002 Tunis, Tunisie.

Protozoan parasites of the genus Leishmania generate severe human diseases termed leishmaniases. Due to their frequency and the severity of certain clinical forms, these diseases represent a major public health problem and limit the economic growth in various developing countries. The presence of Pasteur Institutes in countries with endemic leishmaniasis has provided important incentives to develop a strong public health agenda in the Pasteur scientific community with respect to this important disease. A concerted effort is now coordinated through the recently created LeishRIIP platform (www.leishriip.org), which aims to identify synergies and complementary expertise between the eleven members of the international network of Pasteur Institutes working on various aspects of the disease including epidemiology, diagnosis, chemotherapy and vaccination.
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http://dx.doi.org/10.1051/medsci/20132912020DOI Listing
December 2013

MicroRNA expression profile in human macrophages in response to Leishmania major infection.

PLoS Negl Trop Dis 2013 3;7(10):e2478. Epub 2013 Oct 3.

Laboratory of Biochemistry and Cellular Biology (URBC), NARILIS-University of Namur, Namur, Belgium.

Background: Leishmania (L.) are intracellular protozoan parasites able to survive and replicate in the hostile phagolysosomal environment of infected macrophages. They cause leishmaniasis, a heterogeneous group of worldwide-distributed affections, representing a paradigm of neglected diseases that are mainly embedded in impoverished populations. To establish successful infection and ensure their own survival, Leishmania have developed sophisticated strategies to subvert the host macrophage responses. Despite a wealth of gained crucial information, these strategies still remain poorly understood. MicroRNAs (miRNAs), an evolutionarily conserved class of endogenous 22-nucleotide non-coding RNAs, are described to participate in the regulation of almost every cellular process investigated so far. They regulate the expression of target genes both at the levels of mRNA stability and translation; changes in their expression have a profound effect on their target transcripts.

Methodology/principal Findings: We report in this study a comprehensive analysis of miRNA expression profiles in L. major-infected human primary macrophages of three healthy donors assessed at different time-points post-infection (three to 24 h). We show that expression of 64 out of 365 analyzed miRNAs was consistently deregulated upon infection with the same trends in all donors. Among these, several are known to be induced by TLR-dependent responses. GO enrichment analysis of experimentally validated miRNA-targeted genes revealed that several pathways and molecular functions were disturbed upon parasite infection. Finally, following parasite infection, miR-210 abundance was enhanced in HIF-1α-dependent manner, though it did not contribute to inhibiting anti-apoptotic pathways through pro-apoptotic caspase-3 regulation.

Conclusions/significance: Our data suggest that alteration in miRNA levels likely plays an important role in regulating macrophage functions following L. major infection. These results could contribute to better understanding of the dynamics of gene expression in host cells during leishmaniasis.
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http://dx.doi.org/10.1371/journal.pntd.0002478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3789763PMC
May 2014

Composition and anti-oxidant, anti-cancer and anti-inflammatory activities of Artemisia herba-alba, Ruta chalpensis L. and Peganum harmala L.

Food Chem Toxicol 2013 May 16;55:202-8. Epub 2013 Jan 16.

Université de Toulouse, Laboratoire des Interactions Moléculaires et Réactivité Chimique et Photochimique, UMR CNRS 5623, Université Paul-Sabatier, 118 route de Narbonne, F-31062 Toulouse, France.

In this study, biological activities of methanolic extracts from Artemisia herba-alba, Ruta chalpensis L. and Peganum harmala L. plants, collected in Centre of Tunisia, were investigated. Results showed an important phenolic composition of Artemisia herba-alba (123.95±4.3g GAE/kg of dry mass). The extract of this plant showed, using different antioxidant assays (DPPH, ABTS and AAPH/linoleic acid methods) and an IFN-γ/LPS induced RAW 264.7 murine macrophages' assay, the highest antioxidant (IC50 (DPPH assay) 20.64±0.84mg/L) and anti-inflammatory (72% inhibition at 150mg/L) activities, respectively. Excepting Peganum harmala L. extract, the two other extracts showed a high anticancer activity against several cell lines (human bladder carcinoma RT112, human laryngeal carcinoma Hep2 and human myelogenous leukemia K562), for A. herba-laba IC50=81.59±4.4, 59.05±3.66 and 90.96mg/L respectively, but not on normal peripheral blood mononuclear cells. All these biological activities are well correlated with the phenolic contents of these extracts. These findings demonstrate the remarkable potential of these plants as valuable source of antioxidants with exhibit original and interesting anti-inflammatory and anticancer capacities.
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http://dx.doi.org/10.1016/j.fct.2013.01.004DOI Listing
May 2013

Methodology optimizing SAGE library tag-to-gene mapping: application to Leishmania.

BMC Res Notes 2012 Jan 27;5:74. Epub 2012 Jan 27.

Laboratoire d'Immuno-Pathologie, Vaccinologie et Génétique Moléculaire (LIVGM), WHO Collaborating Center for Research and Training in Leishmaniasis, Institut Pasteur de Tunis, 13 place Pasteur BP74 1002, Tunis, Tunisia.

Background: Leishmaniasis are widespread parasitic-diseases with an urgent need for more active and less toxic drugs and for effective vaccines. Understanding the biology of the parasite especially in the context of host parasite interaction is a crucial step towards such improvements in therapy and control. Several experimental approaches including SAGE (Serial analysis of gene expression) have been developed in order to investigate the parasite transcriptome organisation and plasticity. Usual SAGE tag-to-gene mapping techniques are inadequate because almost all tags are normally located in the 3'-UTR outside the CDS, whereas most information available for Leishmania transcripts is restricted to the CDS predictions. The aim of this work is to optimize a SAGE libraries tag-to-gene mapping technique and to show how this development improves the understanding of Leishmania transcriptome.

Findings: The in silico method implemented herein was based on mapping the tags to Leishmania genome using BLAST then mapping the tags to their gene using a data-driven probability distribution. This optimized tag-to-gene mappings improved the knowledge of Leishmania genome structure and transcription. It allowed analyzing the expression of a maximal number of Leishmania genes, the delimitation of the 3' UTR of 478 genes and the identification of biological processes that are differentially modulated during the promastigote to amastigote differentiation.

Conclusion: The developed method optimizes the assignment of SAGE tags in trypanosomatidae genomes as well as in any genome having polycistronic transcription and small intergenic regions.
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http://dx.doi.org/10.1186/1756-0500-5-74DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292834PMC
January 2012

Synthesis of lipophilic tyrosyl esters derivatives and assessment of their antimicrobial and antileishmania activities.

Lipids Health Dis 2012 Jan 20;11:13. Epub 2012 Jan 20.

Laboratoire de Biochimie et de Génie Enzymatique des Lipases, Ecole Nationale d'Ingénieurs de Sfax (ENIS), Route de Soukra, BP 1173, 3038 Sfax, Université de Sfax,Tunisie.

Background: Preparation of tyrosyl lipophilic derivatives was carried out as a response to the food, cosmetic and pharmaceutical industries' increasing demand for new lipophilic antioxidants.

Results: A large series of tyrosyl esters (TyC₂ to TyC₁₈:₁) with increasing lipophilicity was synthesized in a good yield using lipase from Candida antarctica (Novozyme 435). Spectroscopic analyses of purified esters showed that the tyrosol was esterified on the primary hydroxyl group. Synthetized compounds were evaluated for either their antimicrobial activity, by both diffusion well and minimal inhibition concentration (MIC) methods, or their antileishmanial activity against Leishmania major and Leishmania infantum parasite species.Among all the tested compounds, our results showed that only TyC₈, TyC₁₀ and TyC₁₂ exhibited antibacterial and antileishmanial activities. When MIC and IC50 values were plotted against the acyl chain length of each tyrosyl derivative, TyC₁₀ showed a parabolic shape with a minimum value. This nonlinear dependency with the increase of the chain length indicates that biological activities are probably associated to the surfactant effectiveness of lipophilic derivatives.

Conclusion: These results open up potential applications to use medium tyrosyl derivatives surfactants, antioxidants, antimicrobial and antileishmanial compounds in cosmetic, food and pharmaceutical industries.
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http://dx.doi.org/10.1186/1476-511X-11-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292923PMC
January 2012

Colonization of Phlebotomus papatasi changes the effect of pre-immunization with saliva from lack of protection towards protection against experimental challenge with Leishmania major and saliva.

Parasit Vectors 2011 Jul 4;4:126. Epub 2011 Jul 4.

Laboratory of Vector Ecology, Institut Pasteur de Tunis, Tunis, Tunisia.

Background: Sand fly saliva has been postulated as a potential vaccine or as a vaccine component within multi component vaccine against leishmaniasis. It is important to note that these studies were performed using long-term colonized Phlebotomus papatasi. The effect of sand flies colonization on the outcome of Leishmania infection is reported.

Results: While pre-immunization of mice with salivary gland homogenate (SGH) of long-term colonized (F5 and beyond) female Phlebotomus papatasi induced protection against Leishmania major co-inoculated with the same type of SGH, pre-immunization of mice with SGH of recently colonized (F2 and F3) female P. papatasi did not confer protection against L. major co-inoculated with the same type of SGH. Our data showed for the first time that a shift from lack of protection to protection occurs at the fourth generation (F4) during the colonization process of P. papatasi.

Conclusion: For the development of a sand fly saliva-based vaccine, inferences based on long-term colonized populations of sand flies should be treated with caution as colonization of P. papatasi appears to modulate the outcome of L. major infection from lack of protection to protection.
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http://dx.doi.org/10.1186/1756-3305-4-126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3143093PMC
July 2011

EuPathDomains: the divergent domain database for eukaryotic pathogens.

Infect Genet Evol 2011 Jun 4;11(4):698-707. Epub 2010 Nov 4.

Méthodes et Algorithmes pour la Bioinformatique, LIRMM, CNRS, Univ. Montpellier 2, 161 rue Ada, Montpellier Cedex 5, France.

Eukaryotic pathogens (e.g. Plasmodium, Leishmania, Trypanosomes, etc.) are a major source of morbidity and mortality worldwide. In Africa, one of the most impacted continents, they cause millions of deaths and constitute an immense economic burden. While the genome sequence of several of these organisms is now available, the biological functions of more than half of their proteins are still unknown. This is a serious issue for bringing to the foreground the expected new therapeutic targets. In this context, the identification of protein domains is a key step to improve the functional annotation of the proteins. However, several domains are missed in eukaryotic pathogens because of the high phylogenetic distance of these organisms from the classical eukaryote models. We recently proposed a method, co-occurrence domain detection (CODD), that improves the sensitivity of Pfam domain detection by exploiting the tendency of domains to appear preferentially with a few other favorite domains in a protein. In this paper, we present EuPathDomains (http://www.atgc-montpellier.fr/EuPathDomains/), an extended database of protein domains belonging to ten major eukaryotic human pathogens. EuPathDomains gathers known and new domains detected by CODD, along with the associated confidence measurements and the GO annotations that can be deduced from the new domains. This database significantly extends the Pfam domain coverage of all selected genomes, by proposing new occurrences of domains as well as new domain families that have never been reported before. For example, with a false discovery rate lower than 20%, EuPathDomains increases the number of detected domains by 13% in Toxoplasma gondii genome and up to 28% in Cryptospordium parvum, and the total number of domain families by 10% in Plasmodium falciparum and up to 16% in C. parvum genome. The database can be queried by protein names, domain identifiers, Pfam or Interpro identifiers, or organisms, and should become a valuable resource to decipher the protein functions of eukaryotic pathogens.
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http://dx.doi.org/10.1016/j.meegid.2010.09.008DOI Listing
June 2011

Lack of protection of pre-immunization with saliva of long-term colonized Phlebotomus papatasi against experimental challenge with Leishmania major and saliva of wild-caught P. papatasi.

Am J Trop Med Hyg 2010 Sep;83(3):512-4

Laboratory of Vector Ecology, Laboratory of Epidemiology and Ecology of Parasites, and Laboratory of Immuno-Pathology, Vaccinology, and Molecular Genetics, Institut Pasteur de Tunis, Tunis, Tunisia.

Immunity to saliva of Phlebotomus papatasi protects against Leishmania major infection as determined by co-inoculation of parasites with salivary gland homogenates (SGHs) of this vector. These results were obtained with long-term colonized female P. papatasi. We investigated the effect of pre-immunization with SGH of long-term colonized P. papatasi against L. major infection co-inoculated with SGH of wild-caught P. papatasi. Our results showed that pre-exposure to SGH of long-term, colonized P. papatasi do not confer protection against infection with L. major co-inoculated with SGH of wild-caught P. papatasi. These preliminary results strongly suggest that the effectiveness of a vector saliva-based vaccine derived from colonized sand fly populations may be affected by inconsistent immune response after natural exposure.
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http://dx.doi.org/10.4269/ajtmh.2010.09-0687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2929043PMC
September 2010