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46 results on '"Gruenheid, Samantha"'

5. Modeling gene-environment interactions in Parkinson's Disease: Helicobacter pylori infection of Pink1-/- mice induces CD8 T cell-dependent motor and cognitive dysfunction.

Author

Kazanova, Alexandra, primary, Sung, Jacqueline, additional, Oliveira, Nathalia Luisa, additional, Gavino, Christina, additional, Bessaiah, Hicham, additional, Pei, Jessica, additional, Burns, Lindsay, additional, Miller, Willemein, additional, Brouillard-Galipeau, Morgane, additional, Zhu, Lei, additional, Guerra, Lucia Marguerite, additional, Elemeery, Moustafa Nouh, additional, Recinto, Sherilyn Junelle, additional, MacDonald, Adam, additional, Lanoix, Joel, additional, Thibault, Pierre, additional, McBride, Heidi M., additional, Desjardins, Michel, additional, Stratton, Jo Anne, additional, Labrecque, Nathalie, additional, and Gruenheid, Samantha, additional

Published
2024
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7. A Syst-OMICS Approach to Ensuring Food Safety and Reducing the Economic Burden of Salmonellosis.

Author

Emond-Rheault, Jean-Guillaume, Jeukens, Julie, Freschi, Luca, Kukavica-Ibrulj, Irena, Boyle, Brian, Dupont, Marie-Josée, Colavecchio, Anna, Barrere, Virginie, Cadieux, Brigitte, Arya, Gitanjali, Bekal, Sadjia, Berry, Chrystal, Burnett, Elton, Cavestri, Camille, Chapin, Travis K, Crouse, Alanna, Daigle, France, Danyluk, Michelle D, Delaquis, Pascal, Dewar, Ken, Doualla-Bell, Florence, Fliss, Ismail, Fong, Karen, Fournier, Eric, Franz, Eelco, Garduno, Rafael, Gill, Alexander, Gruenheid, Samantha, Harris, Linda, Huang, Carol B, Huang, Hongsheng, Johnson, Roger, Joly, Yann, Kerhoas, Maud, Kong, Nguyet, Lapointe, Gisèle, Larivière, Line, Loignon, Stéphanie, Malo, Danielle, Moineau, Sylvain, Mottawea, Walid, Mukhopadhyay, Kakali, Nadon, Céline, Nash, John, Ngueng Feze, Ida, Ogunremi, Dele, Perets, Ann, Pilar, Ana V, Reimer, Aleisha R, Robertson, James, Rohde, John, Sanderson, Kenneth E, Song, Lingqiao, Stephan, Roger, Tamber, Sandeep, Thomassin, Paul, Tremblay, Denise, Usongo, Valentine, Vincent, Caroline, Wang, Siyun, Weadge, Joel T, Wiedmann, Martin, Wijnands, Lucas, Wilson, Emily D, Wittum, Thomas, Yoshida, Catherine, Youfsi, Khadija, Zhu, Lei, Weimer, Bart C, Goodridge, Lawrence, and Levesque, Roger C

Subjects
Salmonella, antibiotic resistance, bacterial genomics, database, foodborne pathogen, next-generation sequencing, phylogeny, Genetics, Emerging Infectious Diseases, Biodefense, Infectious Diseases, Prevention, Vaccine Related, Foodborne Illness, Digestive Diseases, Human Genome, Infection, Good Health and Well Being, Environmental Science and Management, Soil Sciences, Microbiology
Abstract

The Salmonella Syst-OMICS consortium is sequencing 4,500 Salmonella genomes and building an analysis pipeline for the study of Salmonella genome evolution, antibiotic resistance and virulence genes. Metadata, including phenotypic as well as genomic data, for isolates of the collection are provided through the Salmonella Foodborne Syst-OMICS database (SalFoS), at https://salfos.ibis.ulaval.ca/. Here, we present our strategy and the analysis of the first 3,377 genomes. Our data will be used to draw potential links between strains found in fresh produce, humans, animals and the environment. The ultimate goals are to understand how Salmonella evolves over time, improve the accuracy of diagnostic methods, develop control methods in the field, and identify prognostic markers for evidence-based decisions in epidemiology and surveillance.

Published
2017

9. LRRK2 regulates the activation of the unfolded protein response and antigen presentation in macrophages during inflammation

Author

Fahmy, Ahmed M., primary, Cannon, Tyler, additional, Paredes, Camberly Herdandez, additional, Ahmadi, Ali, additional, Xu, Yong Zhong, additional, Barette, Benoit, additional, Ibrahim, Maha, additional, Lanoix, Joël, additional, Arango-Duque, Guillermo, additional, Schurr, Erwin, additional, Chevet, Eric, additional, Thibault, Pierre, additional, Gruenheid, Samantha, additional, McBride, Heidi, additional, and Desjardins, Michel, additional

Published
2023
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15. The bacterial virulence factor NleA undergoes host‐mediated O‐linked glycosylation.

Author

Burns, Lindsay, Giannakopoulou, Natalia, Zhu, Lei, Xu, Yong Zhong, Khan, Rufaida H., Bekal, Sadjia, Schurr, Erwin, Schmeing, T. Martin, and Gruenheid, Samantha

Subjects
GLYCOSYLATION, MIXED infections, BACTERIAL proteins, HOSTS (Biology), CYTOLOGY
Abstract

Enterohaemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC) are gastrointestinal pathogens responsible for severe diarrheal illness. EHEC and EPEC form "attaching and effacing" lesions during colonization and, upon adherence, inject proteins directly into host intestinal cells via the type III secretion system (T3SS). Injected bacterial proteins have a variety of functions but generally alter host cell biology to favor survival and/or replication of the pathogen. Non‐LEE‐encoded effector A (NleA) is a T3SS‐injected effector of EHEC, EPEC, and the related mouse pathogen Citrobacter rodentium. Studies in mouse models indicate that NleA has an important role in bacterial virulence. However, the mechanism by which NleA contributes to disease remains unknown. We have determined that the following translocation into host cells, a serine and threonine‐rich region of NleA is modified by host‐mediated mucin‐type O‐linked glycosylation. Surprisingly, this region was not present in several clinical EHEC isolates. When expressed in C. rodentium, a non‐modifiable variant of NleA was indistinguishable from wildtype NleA in an acute mortality model but conferred a modest increase in persistence over the course of infection in mixed infections in C57BL/6J mice. This is the first known example of a bacterial effector being modified by host‐mediated O‐linked glycosylation. Our data also suggests that this modification may confer a selective disadvantage to the bacteria during in vivo infection. [ABSTRACT FROM AUTHOR]

Published
2023
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17. RpoN-Based stapled peptides with improved DNA binding suppress Pseudomonas aeruginosa virulence

Author

Paquette, André R., primary, Payne, Sterling R., additional, McKay, Geoffrey A., additional, Brazeau-Henrie, Jordan T., additional, Darnowski, Micheal G., additional, Kammili, Anitha, additional, Bernal, Federico, additional, Mah, Thien-Fah, additional, Gruenheid, Samantha, additional, Nguyen, Dao, additional, and Boddy, Christopher N., additional

Published
2022
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21. The Plasmidome as a Reservoir of Antibiotic Resistance

Author

Emond-Rheault, Jean-Guillaume, Hamel, Jérémie, Jeukens, Julie, Freschi, Luca, Kukavica-Ibrulj, Irena, Boyle, Brian, Tamber, Sandeep, Malo, Danielle, Franz, Eelco, Burnett, Elton, Daigle, France, Arya, Gitanjali, Sanderson, Kenneth, Wiedmann, Martin, Slawson, Robin M, Weadge, Joel T, Stephan, Roger, Bekal, Sadjia, Gruenheid, Samantha, Goodridge, Lawrence D, and Levesque, Roger C

Subjects
hybrid assembly, plasmid, long-read sequencing, Salmonella enterica, antimicrobial resistance
Abstract

The emergence of multidrug-resistant bacterial strains worldwide has become a serious problem for public health over recent decades. The increase in antimicrobial resistance has been expanding via plasmids as mobile genetic elements encoding antimicrobial resistance (AMR) genes that are transferred vertically and horizontally. This study focuses on Salmonella enterica, one of the leading foodborne pathogens in industrialized countries. S. enterica is known to carry several plasmids involved not only in virulence but also in AMR. In the current paper, we present an integrated strategy to detect plasmid scaffolds in whole genome sequencing (WGS) assemblies. We developed a two-step procedure to predict plasmids based on i) the presence of essential elements for plasmid replication and mobility, as well as ii) sequence similarity to a reference plasmid. Next, to confirm the accuracy of the prediction in 1750 S. enterica short-read sequencing data, we combined Oxford Nanopore MinION long-read sequencing with Illumina MiSeq short-read sequencing in hybrid assemblies for 84 isolates to evaluate the proportion of plasmid that has been detected. At least one scaffold with an origin of replication (ORI) was predicted in 61.3% of the Salmonella isolates tested. The results indicated that IncFII and IncI1 ORIs were distributed in many S. enterica serotypes and were the most prevalent AMR genes carrier, whereas IncHI2A/IncHI2 and IncA/C2 were more serotype restricted but bore several AMR genes. Comparison between hybrid and short-read assemblies revealed that 81.1% of plasmids were found in the short-read sequencing using our pipeline. Through this process, we established that plasmids are prevalent in S. enterica and we also substantially expand the AMR genes in the resistome of this species.

Published
2020

23. The Salmonella enterica Plasmidome as a Reservoir of Antibiotic Resistance

Author

Emond-Rheault, Jean-Guillaume, primary, Hamel, Jérémie, additional, Jeukens, Julie, additional, Freschi, Luca, additional, Kukavica-Ibrulj, Irena, additional, Boyle, Brian, additional, Tamber, Sandeep, additional, Malo, Danielle, additional, Franz, Eelco, additional, Burnett, Elton, additional, Daigle, France, additional, Arya, Gitanjali, additional, Sanderson, Kenneth, additional, Wiedmann, Martin, additional, Slawson, Robin M., additional, Weadge, Joel T., additional, Stephan, Roger, additional, Bekal, Sadjia, additional, Gruenheid, Samantha, additional, Goodridge, Lawrence D., additional, and Levesque, Roger C., additional

Published
2020
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24. Combining Whole-Genome Sequencing and Multimodel Phenotyping To Identify Genetic Predictors of Salmonella Virulence

Author

Crouse, Alanna, primary, Schramm, Catherine, additional, Emond-Rheault, Jean-Guillaume, additional, Herod, Adrian, additional, Kerhoas, Maud, additional, Rohde, John, additional, Gruenheid, Samantha, additional, Kukavica-Ibrulj, Irena, additional, Boyle, Brian, additional, Greenwood, Celia M. T., additional, Goodridge, Lawrence D., additional, Garduno, Rafael, additional, Levesque, Roger C., additional, Malo, Danielle, additional, and Daigle, France, additional

Published
2020
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26. MicroRNA-9 Fine-Tunes Dendritic Cell Function by Suppressing Negative Regulators in a Cell-Type-Specific Manner

Author

Cordeiro, Brendan, primary, Jeon, Peter, additional, Boukhaled, Giselle M., additional, Corrado, Mario, additional, Lapohos, Orsolya, additional, Roy, Dominic G., additional, Williams, Kelsey, additional, Jones, Russell G., additional, Gruenheid, Samantha, additional, Sagan, Selena M., additional, and Krawczyk, Connie M., additional

Published
2020
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28. RpoN-Based stapled peptides with improved DNA binding suppress Pseudomonas aeruginosavirulenceElectronic supplementary information (ESI) available. See DOI: 10.1039/d1md00371b

Author

Paquette, André R., Payne, Sterling R., McKay, Geoffrey A., Brazeau-Henrie, Jordan T., Darnowski, Micheal G., Kammili, Anitha, Bernal, Federico, Mah, Thien-Fah, Gruenheid, Samantha, Nguyen, Dao, and Boddy, Christopher N.

Abstract

Stapled peptides have the ability to mimic α-helices involved in protein binding and have proved to be effective pharmacological agents for disrupting protein–protein interactions. DNA-binding proteins such as transcription factors bind their cognate DNA sequences viaan α-helix interacting with the major groove of DNA. We previously developed a stapled peptide based on the bacterial alternative sigma factor RpoN capable of binding the RpoN DNA promoter sequence and inhibiting RpoN-mediated expression in Escherichia coli. We have elucidated a structure–activity relationship for DNA binding by this stapled peptide, improving DNA binding affinity constants in the high nM range. Lead peptides were shown to have low toxicity as determined by their low hemolytic activity at 100 μM and were shown to have anti-virulence activity in a Galleria mellonellamodel of Pseudomonas aeruginosainfection. These findings support further preclinical development of stapled peptides as antivirulence agents targeting P. aeruginosa.

Published
2022
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29. Identification and characterization of OmpT‐like proteases in uropathogenicEscherichia coliclinical isolates

Author

Desloges, Isabelle, primary, Taylor, James A., additional, Leclerc, Jean‐Mathieu, additional, Brannon, John R., additional, Portt, Andrea, additional, Spencer, John D., additional, Dewar, Ken, additional, Marczynski, Gregory T., additional, Manges, Amee, additional, Gruenheid, Samantha, additional, Le Moual, Hervé, additional, and Thomassin, Jenny‐Lee, additional

Published
2019
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30. Culture-Dependent Bioprospecting of Bacterial Isolates From the Canadian High Arctic Displaying Antibacterial Activity

Author

Marcolefas, Evangelos, primary, Leung, Tiffany, additional, Okshevsky, Mira, additional, McKay, Geoffrey, additional, Hignett, Emma, additional, Hamel, Jérémie, additional, Aguirre, Gabriela, additional, Blenner-Hassett, Olivia, additional, Boyle, Brian, additional, Lévesque, Roger C., additional, Nguyen, Dao, additional, Gruenheid, Samantha, additional, and Whyte, Lyle, additional

Published
2019
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31. Parkinson’s disease related proteins PINK1 and Parkin are major regulators of the immune system

Author

Matheoud, Diana, primary, Cannon, Tyler, additional, Voisin, Aurore, additional, Penttinen, Anna-Maija, additional, Ramet, Lauriane, additional, Fahmy, Ahmed, additional, Ducrot, Charles, additional, Laplante, Annie, additional, Bourque, Marie-Josée, additional, Zhu, Lei, additional, Le Campion, Armelle, additional, McBride, Heidi, additional, Gruenheid, Samantha, additional, Trudeau, Louis-Eric, additional, and Desjardins, Michel, additional

Published
2019
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35. Salmonella enterica Prophage Sequence Profiles Reflect Genome Diversity and Can Be Used for High Discrimination Subtyping

Author

Mottawea, Walid, primary, Duceppe, Marc-Olivier, additional, Dupras, Andrée A., additional, Usongo, Valentine, additional, Jeukens, Julie, additional, Freschi, Luca, additional, Emond-Rheault, Jean-Guillaume, additional, Hamel, Jeremie, additional, Kukavica-Ibrulj, Irena, additional, Boyle, Brian, additional, Gill, Alexander, additional, Burnett, Elton, additional, Franz, Eelco, additional, Arya, Gitanjali, additional, Weadge, Joel T., additional, Gruenheid, Samantha, additional, Wiedmann, Martin, additional, Huang, Hongsheng, additional, Daigle, France, additional, Moineau, Sylvain, additional, Bekal, Sadjia, additional, Levesque, Roger C., additional, Goodridge, Lawrence D., additional, and Ogunremi, Dele, additional

Published
2018
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38. Intestinal infection triggers Parkinson's disease-like symptoms in Pink1−/− mice.

Author

Matheoud, Diana, Cannon, Tyler, Voisin, Aurore, Penttinen, Anna-Maija, Ramet, Lauriane, Fahmy, Ahmed M., Ducrot, Charles, Laplante, Annie, Bourque, Marie-Josée, Zhu, Lei, Cayrol, Romain, Le Campion, Armelle, McBride, Heidi M., Gruenheid, Samantha, Trudeau, Louis-Eric, and Desjardins, Michel

Abstract

Parkinson's disease is a neurodegenerative disorder with motor symptoms linked to the loss of dopaminergic neurons in the substantia nigra compacta. Although the mechanisms that trigger the loss of dopaminergic neurons are unclear, mitochondrial dysfunction and inflammation are thought to have key roles1,2. An early-onset form of Parkinson's disease is associated with mutations in the PINK1 kinase and PRKN ubiquitin ligase genes3. PINK1 and Parkin (encoded by PRKN) are involved in the clearance of damaged mitochondria in cultured cells4, but recent evidence obtained using knockout and knockin mouse models have led to contradictory results regarding the contributions of PINK1 and Parkin to mitophagy in vivo5–8. It has previously been shown that PINK1 and Parkin have a key role in adaptive immunity by repressing presentation of mitochondrial antigens9, which suggests that autoimmune mechanisms participate in the aetiology of Parkinson's disease. Here we show that intestinal infection with Gram-negative bacteria in Pink1−/− mice engages mitochondrial antigen presentation and autoimmune mechanisms that elicit the establishment of cytotoxic mitochondria-specific CD8+ T cells in the periphery and in the brain. Notably, these mice show a sharp decrease in the density of dopaminergic axonal varicosities in the striatum and are affected by motor impairment that is reversed after treatment with l-DOPA. These data support the idea that PINK1 is a repressor of the immune system, and provide a pathophysiological model in which intestinal infection acts as a triggering event in Parkinson's disease, which highlights the relevance of the gut–brain axis in the disease10. In mice lacking PINK1, bacterial infection in the intestine results in mitochondrial antigen presentation and generation of CD8+ T cells, and infected mice develop motor impairments, suggesting that PINK1 suppresses autoimmunity. [ABSTRACT FROM AUTHOR]

Published
2019
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45. Characterization of the intestinal microbiota during Citrobacter rodentiuminfection in a mouse model of infection-triggered Parkinson’s disease

Author

Cannon, Tyler, Sinha, Anshul, Trudeau, Louis-Eric, Maurice, Corinne F., and Gruenheid, Samantha

Abstract

ABSTRACTParkinson’s disease (PD) is a neurodegenerative disorder that has been shown to be influenced by the intestinal milieu. The gut microbiota is altered in PD patients, and murine studies have begun suggesting a causative role for the gut microbiota in progression of PD. We have previously shown that repeated infection with the intestinal murine pathogen Citrobacter rodentiumresulted in the development of PD-like pathology in Pink1−/-mice compared to wild-type littermates. This addendum aims to expand this work by characterizing the gut microbiota during C. rodentiuminfection in our Pink1−/-PD model. We observed little disturbance to the fecal microbiota diversity both between infection timepoints and between Pink1−/-and wild-type control littermates. However, the level of short-chain fatty acids appeared to be altered over the course of infection with butyric acid significantly increasing in Pink1−/-mice and isobutyric acid increasing in wild-type mice.

Published
2020
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46. Systematic Analysis of Two-Component Systems in Citrobacter rodentiumReveals Positive and Negative Roles in Virulence

Author

Thomassin, Jenny-Lee, Leclerc, Jean-Mathieu, Giannakopoulou, Natalia, Zhu, Lei, Salmon, Kristiana, Portt, Andrea, Daigle, France, Le Moual, Hervé, and Gruenheid, Samantha

Abstract

ABSTRACTCitrobacter rodentiumis a murine pathogen used to model intestinal infections caused by the human diarrheal pathogens enterohemorrhagic and enteropathogenic Escherichia coli. During infection, bacteria use two-component systems (TCSs) to detect changing environmental cues within the host, allowing for rapid adaptation by altering the expression of specific genes. In this study, 26 TCSs were identified in C. rodentium, and quantitative PCR (qPCR) analysis showed that they are all expressed during murine infection. These TCSs were individually deleted, and the in vitroand in vivoeffects were analyzed to determine the functional consequences. In vitroanalyses only revealed minor differences, and surprisingly, type III secretion (T3S) was only affected in the ΔarcAstrain. Murine infections identified 7 mutants with either attenuated or increased virulence. In agreement with the in vitroT3S assay, the ΔarcAstrain was attenuated and defective in colonization and cell adherence. The ΔrcsBstrain was among the most highly attenuated strains. The decrease in virulence of this strain may be associated with changes to the cell surface, as Congo red binding was altered, and qPCR revealed that expression of the wcaAgene, which has been implicated in colanic acid production in other bacteria, was drastically downregulated. The ΔuvrYstrain exhibited increased virulence compared to the wild type, which was associated with a significant increase in bacterial burden within the mesenteric lymph nodes. The systematic analysis of virulence-associated TCSs and investigation of their functions during infection may open new avenues for drug development.

Published
2016
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