François-Xavier Campbell-Valois

François-Xavier Campbell-Valois
University of Ottawa · Department of Chemistry and Biomolecular Sciences

Ph.D.

About

53
Publications
53,229
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Introduction
I am an Associate Professor in the Department of Chemistry and Biomolecular Sciences at the University of Ottawa, Canada. In my research group, we are interested about all aspects of microbial pathogenesis. In particular, we study the microbiology, molecular biology and cell biology aspects of infection by the human bacterial pathogen Shigella spp.
Additional affiliations
May 2021 - present
University of Ottawa
Position
  • Professor (Associate)
July 2015 - April 2020
University of Ottawa
Position
  • Professor (Assistant)
November 2014 - April 2015
Collège de France
Position
  • PostDoc Position
Education
May 1999 - April 2006
Université de Montréal
Field of study
  • Molecular Biology
September 1994 - June 1997
Université de Montréal
Field of study
  • Biochemistry

Publications

Publications (53)
Article
Full-text available
Numerous pathogenic Gram-negative bacteria use a type three secretion apparatus (T3SA) to translocate effector proteins into host cells. Detecting and monitoring the T3SA of intracellular bacteria within intact host cells has been challenging. Taking advantage of the tight coupling between T3S effector-gene transcription and T3SA activity in Shigel...
Article
Shigella spp. are enterobacteria that invade human colonic mucosal cells using their Type Three Secretion Apparatus (T3SA). Shigella spp. possess a large plasmid that encodes most of its virulence factors and has been the focus of seminal work that defined the T3SA regulon. Thus, a global assessment of the transcriptional response regulated by the...
Article
Full-text available
Shigella spp. are bacterial pathogens that invade the human colonic mucosa using a Type III Secretion Apparatus (T3SA), a proteinaceous device activated upon contact with host cells. Active T3SAs translocate proteins that carve the intracellular niche of Shigella spp.. Nevertheless, the activation state of the T3SA has not been addressed in vivo. H...
Article
Full-text available
Shigella spp. are one of the leading causes of infectious diarrheal diseases. They are Escherichia coli pathovars that are characterized by the harboring of a large plasmid that encodes most virulence genes, including a type III secretion system (T3SS). The archetypal element of the T3SS is the injectisome, a syringe-like nanomachine composed of ap...
Article
Full-text available
Shigella is an Escherichia coli pathovar that colonizes the cytosol of mucosal cells in the human large intestine. To do this, Shigella uses a Type III Secretion Apparatus (T3SA) to translocate several proteins into host cells. The T3SA and its substrates are encoded by genes of the virulence plasmid pINV or by chromosomal genes derived thereof. We...
Article
Full-text available
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
Preprint
Full-text available
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
Preprint
Full-text available
the PDF can be download freely on pubmed. https://pubmed.ncbi.nlm.nih.gov/33634751/
Cover Page
Full-text available
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
Article
Full-text available
Pathogenic enterobacteria face various oxygen (O2) levels during intestinal colonization from the O2-deprived lumen to oxygenated tissues. Using Shigella flexneri as a model, we have previously demonstrated that epithelium invasion is promoted by O2 in a type III secretion system-dependent manner. However, subsequent pathogen adaptation to tissue o...
Article
The autophagy pathway is an essential facet of the innate immune response, capable of rapidly targeting intracellular bacteria. However, the initial signaling regulating autophagy induction in response to pathogens remains largely unclear. Here, we report that AMPK, an upstream activator of the autophagy pathway, is stimulated upon detection of pat...
Article
Full-text available
Enterobacteriaceae are a large family of Gram-negative, non-spore-forming bacteria. Although many species exist as part of the natural flora of animals including humans, some members are associated with both intestinal and extraintestinal diseases. In this review, we focus on members of this family that have important roles in human disease: Salmon...
Article
Full-text available
Many human Gram-negative bacterial pathogens express a Type Three Secretion Apparatus (T3SA), including among the most notorious Shigella spp., Salmonella enterica, Yersinia enterocolitica and enteropathogenic Escherichia coli (EPEC). These bacteria express on their surface multiple copies of the T3SA that mediate the delivery into host cells of sp...
Data
Mass spectrometry results. Quantification of peptide number and abundance in ipaD versus mxiD samples for the 3 biological replicates. High, intermediate and low confidence predictions are listed. Protein identification is given as GI accession number. NA: non applicable (one of the samples did not yield any peptide matching a protein hit). (DOCX)
Data
Expression of β-lactamase chimeric proteins initiated from different Shine and Dalgarno (SD) sequences. WT Shigella lysates were analysed by immunoblotting with anti-β-lactamase antibody. Load equivalent to a bacterial culture OD600 of 0.6 for each lane. cons: consensus SD; end: endogenous SD. Chimeric proteins tested and their expected molecular w...
Data
β-lactamase secretion assay control experiments for the WT Shigella strain used to assess translocation of substrates identified by MS. (A) WT Shigella lysates were analysed by immunoblotting with anti-β-lactamase antibody. Load equivalent to a bacterial culture OD600 of 0.2 for each condition. See legend of Fig 3A for expected sizes. (B) Supernata...
Data
Plaque assay with single-mutant Shigella strains. Plaques resulting from invasion, intracellular replication and cell-to-cell spread within Caco-2/TC7 monolayers were enumerated (A) and their area measured (B) three days later. Data are from 4 independent experiments. No statistical difference between the different strains was found, as assessed by...
Data
Assessment of β-lactamase assay reliability by measuring secretion and translocation of antitoxin and chaperones. (A) Lysates of WT Shigella expressing antitoxin and chaperone β-lactamase chimeric proteins were analysed by immunoblotting with anti-β-lactamase antibody. Load equivalent to a bacterial culture OD600 of 0.2 for each condition. See Fig...
Data
Quantification of Orf-bla expression in bacterial lysates. Three independent sets of protein lysates from Orf-bla-expressing ipaD (A) and WT (B) Shigella were analysed by immunoblotting with anti-β-lactamase antibody. Intensity from the highest molecular weight species was quantified as a proportion of protein quantity measured in Orf182-bla-expres...
Data
Assessment of β-lactamase assay reliability for measuring secretion by ipaD strains of substrates identified by MS. (A) Supernatants obtained after spinning of raw and sonicated sub-cultures (sub.) of ipaD strains expressing Orf182-bla, OspI-bla and Orf48-bla were incubated with nitrocefin. Enzymatic activity was calculated based on measurement of...
Article
Full-text available
The enteroinvasive bacterium Shigella is a facultative intracellular bacterium known, in vitro, to invade a large diversity of cells through the delivery of virulence effectors into the cell cytoplasm via a type III secretion system (T3SS). Here, we provide evidence that the injection of T3SS effectors does not necessarily result in cell invasion....
Chapter
Proteins are the most abundant polymers in living organisms and major constituents of biological nanocomposites (bio-nanocomposites). Twenty types of various amino acids, differing only by the nature of their sidechains, constitute the basic building blocks of proteins and are linked together by peptide bonds. The specific sequential order of amino...
Article
Full-text available
Invasion and multiplication of the facultative, cytosolic, enteropathogen Shigella flexneri within the colonic epithelial lining leads to an acute inflammatory response, fever and diarrhea. During the inflammatory process, infected cells are subjected to numerous stresses including heat, oxidative stress and genotoxic stress. The evolutionarily con...
Article
Full-text available
Shigella spp. are Gram-negative bacterial pathogens that infect human colonic epithelia and cause bacterial dysentery. These bacteria express multiple copies of a syringe-like protein complex, the Type Three Secretion apparatus (T3SA), which is instrumental in the etiology of the disease. The T3SA triggers the plasma membrane (PM) engulfment of the...
Article
Full-text available
Few studies within the pathogenic field have used advanced imaging and analytical tools to quantitatively measure pathogenicity in vivo. In this work, we present a novel approach for the investigation of host-pathogen processes based on medium-throughput 3D fluorescence imaging. The guinea pig model for Shigella flexneri invasion of the colonic muc...
Article
Full-text available
Unlabelled: The enteropathogenic bacterium Shigella flexneri uses a type 3 secretion apparatus (T3SA) to transfer proteins dubbed translocators and effectors inside host cells, inducing bacterial uptake and subsequent lysis of the entry vacuole. Once in the cytoplasm, the outer membrane protein IcsA induces actin polymerization, enabling cytoplasm...
Book
Full-text available
Dans cet ouvrage, les notions de base en biologie structurale du repliement des protéines sont présentées dans une perspective historique et théorique. Dans la seconde partie, les résultats de nos travaux sur le repliement du domaine liant Ras de la protéine Raf sont décrits. En bref, nous avons utilisé une approche de librairies de codons dégénéré...
Technical Report
Full-text available
Gram negative bacterial pathogens, such as Shigella flexneri, which possess a Type Three Secretion System (T3SS), are able to transfer bacterial proteins, dubbed translocators and effectors, from their cytoplasm into the cytoplasm of their host cells using a syringe like needle complex. For Shigella, it has been shown that during cellular invasion,...
Technical Report
Full-text available
Many gram-negative bacterial pathogens, including Shigella flexneri, are able to translocate bacterial proteins, dubbed effectors, across the host cell plasma membrane into the host cell cytosol using a syringe-like structure, the type three secretion apparatus (T3SA). While some bacteria use their T3SA to modulate their phagosomal environment (Sal...
Data
Full-text available
Supplemental Information for Cell Host and Microbe (2014) vol. 15, pp177-89. Numerous pathogenic Gram-negative bacteria use a type three secretion apparatus (T3SA) to translocate effector proteins into host cells. Detecting and monitoring the T3SA of intracellular bacteria within intact host cells has been challenging. Taking advantage of the tigh...
Article
Full-text available
During the infectious process, bacterial pathogens are subject to changes in environmental conditions such as nutrient availability, immune response challenges, bacterial density and physical contacts with targeted host cells. These conditions occur in the colonized organs, in diverse regions within infected tissues or even at the subcellular level...
Article
Shigella invasion of its human host is assisted by T3SS-delivered effector proteins. The OspG effector kinase binds ubiquitin and ubiquitin-loaded E2-conjugating enzymes, including UbcH5b and UbcH7, and attenuates the host innate immune NF-kB signaling. We present the structure of OspG bound to the UbcH7∼Ub conjugate. OspG has a minimal kinase fold...
Article
https://bio-protocol.org/e1271?sid=23442c2f-9d21-4e4c-831d-0cecddab1a65&sousouid=20201005075937112&ptype=0&px=2&intwzid=1271
Article
Full-text available
Phagosomes, by killing and degrading pathogens for antigen presentation, are organelles implicated in key aspects of innate and adaptive immunity. Although it has been well established that phagosomes consist of membranes from the plasma membrane, endosomes, and lysosomes, the notion that the endoplasmic reticulum (ER) membrane could play an import...
Article
Full-text available
Biochemical 'pathways' are systems of dynamically assembling and disassembling protein complexes, and thus, much of modern biological research is concerned with how, when and where proteins interact with other proteins involved in biochemical processes. The demand for simple approaches to study protein-protein interactions, particularly on a large...
Article
The ras binding domain (RBD) of the Ser/Thr kinase c-Raf/Raf-1 spans 78 residues and adopts a structure characteristic of the β-grasp ubiquitin-like topology. Recently, the primary sequence of Raf RBD has been nearly exhaustively mutated experimentally by insertion of stretches of degenerate codons, which revealed sequence conservation and hydropho...
Article
Full-text available
The protein-engineering field is mainly concerned with the design of novel enzyme activities or folds and with understanding the fundamental sequence determinants of protein folding and stability. Much effort has been put into the design of methods to generate and screen libraries of polypeptides. Screening for the ability of proteins to bind with...
Article
The contributions of specific residues to the delicate balance between function, stability and folding rates could be determined, in part by [corrected] comparing the sequences of structures having identical folds, but insignificant sequence homology. Recently, we have devised an experimental strategy to thoroughly explore residue substitutions con...
Article
Full-text available
Most protein topologies rarely occur in nature, thus limiting our ability to extract sequence information that could be used to predict structure, function, and evolutionary constraints on protein folds. In principle, the sequence diversity explored by a given protein topology could be expanded by introducing sequence perturbations and selecting va...
Article
Systematic studies of the organization of biochemical networks that make up the living cell can be defined by studying the organization and dynamics of protein interaction networks (PINs). Here, we describe recent conceptual and experimental advances that can achieve this aim and how chemical perturbations of interactions can be used to define the...
Article
This chapter presents the basic concept of protein fragment complementation assays (PCAs) and how they are designed, with particular attention to the system developed based on murine dihydrofolate reductase (mDHFR). It then discusses several applications of the assay, including a simple, large-scale library-versus-library screening strategy in Esch...
Article
Full-text available
Reassembly of enzymes from peptide fragments has been used as a strategy for understanding the evolution, folding, and role of individual subdomains in catalysis and regulation of activity. We demonstrate an oligomerization-assisted enzyme reassembly strategy whereby fragments are covalently linked to independently folding and interacting domains w...

Questions

Questions (5)
Question
I am simply looking for a website that will allow generating a graphical map of a prokaryote chromosome (>4Mb) or large plasmid from a Genbank reference number. Any suggestions very much appreciated.
Question
We would like to work with very short antibiotic resistance gene that are useable as selection marker in the bacteria Escherichia coli and potentially other Gram-negative strains. The shortest resistance gene that I know is the bleomycin resistance gene, which coding sequence is approximately 400 base pairs. 
Does anybody know a shorter or equivalent size resistant gene useable in E. coli?
Question
I have a short sequence that was derived from a plasmid and I want to find back from where it originates by searching for homology of this short sequence against a database of plasmids or expression plasmids (man designed). Using BLAST did not work because I could not found a way to limit the search to expression plasmid.

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Projects

Projects (3)
Project
Determine new shigella effectors and their implication in pathogenesis
Project
Take advantage of the perturbations associated to the presence of microorganisms (symbionts or pathogens) interacting naturally with specific tissues to enlighten novel facets of the mechanisms underlying their building and their maintenance over time.