7 results on '"Boulanger, Martin J."'
Search Results
2. The FAR protein family of parasitic nematodes.
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Parks, Sophia C., Nguyen, Susan, Boulanger, Martin J., and Dillman, Adler R.
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NEMATODES , *PROTEINS , *RETINOL-binding proteins , *FATTY acids , *VITAMIN A , *PLANT nematodes - Abstract
Fatty acid–and retinol-binding proteins (FARs) belong to a unique family of excreted/secreted proteins (ESPs) found exclusively in nematodes. Much of our understanding of these proteins, however, is limited to their in vitro binding characteristics toward various fatty acids and retinol and has provided little insight into their in vivo functions or mechanisms. Recent research, however, has shown that FARs elicit an immunomodulatory role in plant and animal model systems, likely by sequestering lipids involved in immune signaling. This alludes to the intricate relationship between parasitic nematode effectors and their hosts. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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3. The Trypanosoma brucei MISP family of invariant proteins is co-expressed with BARP as triple helical bundle structures on the surface of salivary gland forms, but is dispensable for parasite development within the tsetse vector.
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Casas-Sanchez, Aitor, Ramaswamy, Raghavendran, Perally, Samïrah, Haines, Lee R., Rose, Clair, Aguilera-Flores, Marcela, Portillo, Susana, Verbeelen, Margot, Hussain, Shahid, Smithson, Laura, Yunta, Cristina, Lehane, Michael J., Vaughan, Sue, van den Abbeele, Jan, Almeida, Igor C., Boulanger, Martin J., and Acosta-Serrano, Álvaro
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TRYPANOSOMA , *SALIVARY glands , *HELICAL structure , *TRYPANOSOMA brucei , *SURFACE structure , *MEMBRANE glycoproteins - Abstract
Trypanosoma brucei spp. develop into mammalian-infectious metacyclic trypomastigotes inside tsetse salivary glands. Besides acquiring a variant surface glycoprotein (VSG) coat, little is known about the metacyclic expression of invariant surface antigens. Proteomic analyses of saliva from T. brucei-infected flies identified, in addition to VSG and Brucei Alanine-Rich Protein (BARP) peptides, a family of GPI-anchored surface proteins herein named as Metacyclic Invariant Surface Proteins (MISP) because of its predominant expression on the surface of metacyclic trypomastigotes. The MISP family is encoded by five paralog genes with >80% protein identity, which are exclusively expressed by salivary gland stages of the parasite and peak in metacyclic stage, as shown by confocal microscopy and immuno-high resolution scanning electron microscopy. Crystallographic analysis of a MISP isoform (MISP360) and a high confidence model of BARP revealed a triple helical bundle architecture commonly found in other trypanosome surface proteins. Molecular modelling combined with live fluorescent microscopy suggests that MISP N-termini are potentially extended above the metacyclic VSG coat, and thus could be tested as a transmission-blocking vaccine target. However, vaccination with recombinant MISP360 isoform did not protect mice against a T. brucei infectious tsetse bite. Lastly, both CRISPR-Cas9-driven knock out and RNAi knock down of all MISP paralogues suggest they are not essential for parasite development in the tsetse vector. We suggest MISP may be relevant during trypanosome transmission or establishment in the vertebrate's skin. Author summary: The Trypanosoma brucei group of parasites are exclusively transmitted to the vertebrate host by the tsetse vector alongside insect saliva. To better understand trypanosome transmission, we investigated the protein composition of T. brucei-infected tsetse saliva using a mass spectrometry proteomics approach. We found that, in addition to proteins from tsetse saliva and Sodalis glossinidius (a bacterial tsetse symbiont), trypanosome-infected saliva contains several parasite surface glycoproteins, including a partially characterized family of invariant proteins herein named Metacyclic Invariant Surface Proteins (MISP). We show that MISP is primarily expressed, together with mVSG and BARP, on the surface of the infectious metacyclic stage of T. brucei. Its triple helix bundle architecture appears tethered to the outer membrane by an extended GPI-anchored C-terminal tail that putatively projects MISP above the VSG coat. Our findings provide new insights into the surface architecture of the T. brucei metacyclic stage and describes the challenges associated with developing transmission-blocking vaccines against tsetse-transmitted trypanosomes. [ABSTRACT FROM AUTHOR]
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- 2023
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4. Parasitic nematode fatty acid- and retinol-binding proteins compromise host immunity by interfering with host lipid signaling pathways.
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Parks, Sophia C., Nguyen, Susan, Nasrolahi, Shyon, Bhat, Chaitra, Juncaj, Damian, Lu, Dihong, Ramaswamy, Raghavendran, Dhillon, Harpal, Fujiwara, Hideji, Buchman, Anna, Akbari, Omar S., Yamanaka, Naoki, Boulanger, Martin J., and Dillman, Adler R.
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CELLULAR signal transduction , *NEMATODE infections , *SMALL molecules , *CARRIER proteins , *CAENORHABDITIS elegans , *RETINOL-binding proteins - Abstract
Parasitic nematodes cause significant morbidity and mortality globally. Excretory/secretory products (ESPs) such as fatty acid- and retinol- binding proteins (FARs) are hypothesized to suppress host immunity during nematode infection, yet little is known about their interactions with host tissues. Leveraging the insect parasitic nematode, Steinernema carpocapsae, we describe here the first in vivo study demonstrating that FARs modulate animal immunity, causing an increase in susceptibility to bacterial co-infection. Moreover, we show that FARs dampen key components of the fly immune response including the phenoloxidase cascade and antimicrobial peptide (AMP) production. Our data also reveal that FARs deplete lipid signaling precursors in vivo as well as bind to these fatty acids in vitro, suggesting that FARs elicit their immunomodulatory effects by altering the availability of lipid signaling molecules necessary for an efficient immune response. Collectively, these data support a complex role for FARs in immunosuppression in animals and provide detailed mechanistic insight into parasitism in phylum Nematoda. Author summary: A central aspect of parasitic nematode success is their ability to modify host biology, including evasion and/or subversion of host immunity. Modulation of host biology and the pathology caused by parasitic nematodes is largely effected through the release of proteins and small molecules. There are hundreds of proteins released by nematodes during an infection and few have been studied in detail. Fatty acid- and retinol-binding proteins (FARs) are a unique protein family, found only in nematodes and some bacteria, and are released during nematode infection. We report that nematode FARs from S. carpocapsae, C. elegans and A. ceylanicum dampen fly immunity decreasing resistance to infection. Mechanistically, this is achieved through modulation of the phenoloxidase cascade and antimicrobial peptide production. Furthermore, FARs alter the availability of lipid immune signaling precursors in vivo and show binding specificity in vitro. [ABSTRACT FROM AUTHOR]
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- 2021
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5. The Structure of Treponema pallidum Tp0751 (Pallilysin) Reveals a Non-canonical Lipocalin Fold That Mediates Adhesion to Extracellular Matrix Components and Interactions with Host Cells.
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Parker, Michelle L., Houston, Simon, Pětrošová, Helena, Lithgow, Karen V., Hof, Rebecca, Wetherell, Charmaine, Kao, Wei-Chien, Lin, Yi-Pin, Moriarty, Tara J., Ebady, Rhodaba, Cameron, Caroline E., and Boulanger, Martin J.
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DIAGNOSIS of syphilis , *SYPHILIS , *MEDICAL microbiology , *TREPONEMA pallidum , *SYPHILIS treatment , *PATIENTS - Abstract
Syphilis is a chronic disease caused by the bacterium Treponema pallidum subsp. pallidum. Treponema pallidum disseminates widely throughout the host and extravasates from the vasculature, a process that is at least partially dependent upon the ability of T. pallidum to interact with host extracellular matrix (ECM) components. Defining the molecular basis for the interaction between T. pallidum and the host is complicated by the intractability of T. pallidum to in vitro culturing and genetic manipulation. Correspondingly, few T. pallidum proteins have been identified that interact directly with host components. Of these, Tp0751 (also known as pallilysin) displays a propensity to interact with the ECM, although the underlying mechanism of these interactions remains unknown. Towards establishing the molecular mechanism of Tp0751-host ECM attachment, we first determined the crystal structure of Tp0751 to a resolution of 2.15 Å using selenomethionine phasing. Structural analysis revealed an eight-stranded beta-barrel with a profile of short conserved regions consistent with a non-canonical lipocalin fold. Using a library of native and scrambled peptides representing the full Tp0751 sequence, we next identified a subset of peptides that showed statistically significant and dose-dependent interactions with the ECM components fibrinogen, fibronectin, collagen I, and collagen IV. Intriguingly, each ECM-interacting peptide mapped to the lipocalin domain. To assess the potential of these ECM-coordinating peptides to inhibit adhesion of bacteria to host cells, we engineered an adherence-deficient strain of the spirochete Borrelia burgdorferi to heterologously express Tp0751. This engineered strain displayed Tp0751 on its surface and exhibited a Tp0751-dependent gain-of-function in adhering to human umbilical vein endothelial cells that was inhibited in the presence of one of the ECM-interacting peptides (p10). Overall, these data provide the first structural insight into the mechanisms of Tp0751-host interactions, which are dependent on the protein’s lipocalin fold. [ABSTRACT FROM AUTHOR]
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- 2016
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6. Structural and Functional Insights into the Malaria Parasite Moving Junction Complex.
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Vulliez-Le Normand, Brigitte, Tonkin, Michelle L., Lamarque, Mauld H., Langer, Susann, Hoos, Sylviane, Roques, Magali, Saul, Frederick A., Faber, Bart W., Bentley, Graham A., Boulanger, Martin J., and Lebrun, Maryse
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APICOMPLEXA , *HOST-parasite relationships , *APICAL membrane antigen 1 , *CRYSTAL structure , *BINDING sites , *GENETIC mutation , *RECOMBINANT proteins , *GENETIC polymorphisms - Abstract
Members of the phylum Apicomplexa, which include the malaria parasite Plasmodium, share many features in their invasion mechanism in spite of their diverse host cell specificities and life cycle characteristics. The formation of a moving junction (MJ) between the membranes of the invading apicomplexan parasite and the host cell is common to these intracellular pathogens. The MJ contains two key parasite components: the surface protein Apical Membrane Antigen 1 (AMA1) and its receptor, the Rhoptry Neck Protein (RON) complex, which is targeted to the host cell membrane during invasion. In particular, RON2, a transmembrane component of the RON complex, interacts directly with AMA1. Here, we report the crystal structure of AMA1 from Plasmodium falciparum in complex with a peptide derived from the extracellular region of PfRON2, highlighting clear specificities of the P. falciparum RON2-AMA1 interaction. The receptor-binding site of PfAMA1 comprises the hydrophobic groove and a region that becomes exposed by displacement of the flexible Domain II loop. Mutations of key contact residues of PfRON2 and PfAMA1 abrogate binding between the recombinant proteins. Although PfRON2 contacts some polymorphic residues, binding studies with PfAMA1 from different strains show that these have little effect on affinity. Moreover, we demonstrate that the PfRON2 peptide inhibits erythrocyte invasion by P. falciparum merozoites and that this strong inhibitory potency is not affected by AMA1 polymorphisms. In parallel, we have determined the crystal structure of PfAMA1 in complex with the invasion-inhibitory peptide R1 derived by phage display, revealing an unexpected structural mimicry of the PfRON2 peptide. These results identify the key residues governing the interactions between AMA1 and RON2 in P. falciparum and suggest novel approaches to antimalarial therapeutics. [ABSTRACT FROM AUTHOR]
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- 2012
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7. The RON2-AMA1 Interaction is a Critical Step in Moving Junction-Dependent Invasion by Apicomplexan Parasites.
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Lamarque, Mauld, Besteiro, Sébastien, Papoin, Julien, Roques, Magali, Vulliez-Le Normand, Brigitte, Morlon-Guyot, Juliette, Dubremetz, Jean-François, Fauquenoy, Sylvain, Tomavo, Stanislas, Faber, Bart W., Kocken, Clemens H., Thomas, Alan W., Boulanger, Martin J., Bentley, Graham A., and Lebrun, Maryse
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PROTEINS , *CELL communication , *CELL junctions , *APICOMPLEXA , *PARASITES , *CELL physiology - Published
- 2011
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