Louis-Charles Fortier

Université de Sherbrooke | UdeS · Department of Microbiology and Infectious Diseases

Bacteriophages, or simply phages, are viruses infecting bacteria. With an estimated 10 ( 31) particles in the biosphere, phages outnumber bacteria by a factor of at least 10 and not surprisingly, they influence the evolution of most bacterial species, sometimes in unexpected ways. "Temperate" phages have the ability to integrate into the chromosome...

Clostridium difficile is a Gram-positive pathogen infecting humans and animals. Recent studies suggest that animals could represent potential reservoirs of C. difficile that could then transfer to humans. Temperate phages contribute to the evolution of most bacteria, for example, by promoting the transduction of virulence, fitness, and antibiotic r...

Bacteriophages are present in virtually all ecosystems and bacteria have developed multiple antiphage strategies to counter their attacks. Clostridium difficile is an important pathogen causing severe intestinal infections in humans and animals. Here we show that the conserved cell-surface protein CwpV provides antiphage protection in C. difficile....

Bacteriophages (phages) are present in almost, if not all ecosystems. Some of these bacterial viruses are present as latent “prophages,” either integrated within the chromosome of their host, or as episomal DNAs. Since prophages are ubiquitous throughout the bacterial world, there has been a sustained interest in trying to understand their contribu...

Therapeutic bacteriophages (phages) are being considered as alternatives in the fight against Clostridioides difficile infections. To be efficient, phages should have a wide host range, buthe lack of knowledge about the cell receptor used by C. difficile phages hampers the rational design of phage cocktails. Recent reports suggested that the C. dif...

Clostridioides difficile (C. difficile) strains belonging to the epidemic BI/NAP1/027 (RT027) group have been associated with increased transmissibility and disease severity. In addition to the major toxin A and toxin B virulence factors, RT027 strains also encode the CDT binary toxin. Our lab previously identified a toxigenic RT027 isolate, ST1-75...

With the antibiotic crisis and the rise in antimicrobial resistance worldwide, new therapeutic alternatives are urgently needed. Phage therapy represents one of the most promising alternatives but for some pathogens, such as Clostridioides difficile , important challenges are being faced. The perspective of phage therapy to treat C. difficile infec...

Copper has a long history of use as a biocidal agent. Recent studies have demonstrated that incorporating graphene into copper coatings improves their antibacterial properties. However, the implementation of copper-graphene composite coatings is currently limited by the cost and scarcity of copper, as well as the difficulty of achieving a homogeneo...

Viruses that infect bacteria (bacteriophages or phages) attach to the host cell envelope, inject their genetic material into the host cytosol and either persist as prophage or hijack the host machinery to produce progeny virions. Attachment is mediated through phage receptor binding proteins that are specific for different host cell surface molecul...

Clostridioides difficile produces toxins that damage the colonic epithelium, causing colitis. Variation in disease severity is poorly understood and has been attributed to host factors and virulence differences between C. difficile strains. We test 23 epidemic ST1 C. difficile clinical isolates for their virulence in mice. All isolates encode a com...

Klebsiella oxytoca is a Gram-negative bacterium found in faecal microbiota and known to cause several infections in humans, including antibiotic-associated hemorrhagic colitis. We present here a case of colitis caused by K. oxytoca toxin producing strains that evolved in chronic diarrhea successfully treated by fecal microbiota transplant.

The importance of the inert environment in the transmission of pathogens has been reassessed in recent years. To reduce cross-contamination, new biocidal materials used in high touch surfaces (e.g., stair railings, door handles) have been developed. However, their impact on skin remains poorly described. The present study aimed to evaluate the anti...

NOT PUBLISHED AT AUTHOR’S REQUEST Disclosure of Interest None Declared

Clostridioides difficile (C. difficile), a leading cause of nosocomial infection, produces toxins that damage the colonic epithelium and results in colitis that varies from mild to fulminant. Variation in disease severity is poorly understood and has been attributed to host factors (age, immune competence and intestinal microbiome composition) and/...

The effect of Western diets in the gastrointestinal system is largely mediated by their ability to promote alterations in the immunity and physiology of the intestinal epithelium, and to affect the composition of the commensal microbiota. To investigate the response of the colonic epithelium to high‐fat/high‐cholesterol diets (HFHCDs), we evaluated...

Therapeutic bacteriophages (phages) are being considered as alternatives in the fight against Clostridioides difficile infections. To be efficient, phages should have a wide host range, but the lack of knowledge about the cell receptor used by C. difficile phages hampers the rational design of phage cocktails. Recent reports suggested that the C. d...

Inflammatory bowel diseases (IBDs) are characterized by abnormal, non‐antigen specific chronic inflammation of unknown etiology. Genome‐wide association studies show that many IBD genetic susceptibility loci map to immune function genes and compelling evidence indicate that environmental factors play a critical role in IBD pathogenesis. Clinical an...

Infections caused by multidrug-resistant bacteria are a major public health problem. Their transmission is strongly linked to cross contamination via inert surfaces, which can serve as reservoirs for pathogenic microorganisms. To address this problem, antibacterial materials applied to high-touch surfaces have been developed. However, reaching a ra...

Clostridioides difficile is the main cause of nosocomial antibiotic-associated diarrhoea. There is a need for new antimicrobials to tackle this pathogen. Guanine riboswitches have been proposed as promising new antimicrobial targets, but experimental evidence of their importance in C. difficile is missing. The genome of C. difficile encodes four di...

Viruses that infect bacteria (phages) are increasingly recognized for their importance in diverse ecosystems but identifying and annotating them in large-scale sequence datasets is still challenging. Although efficient scalable virus identification tools are emerging, defining the exact ends (termini) of phage genomes is still particularly difficul...

Objective Many women with pelvic organ prolapse opt for a pessary, and some of these women develop erosions of the vaginal mucosa. Ongoing erosions might lead to the discontinuation of this otherwise effective, non-invasive, and inexpensive treatment. The objectives of this study were to investigate the differences in vaginal pH and variations of t...

Clostridium difficile, now reclassified as Clostridioides difficile, is the causative agent of C. difficile infections (CDI). CDI is particularly challenging in healthcare settings because highly resistant spores of the bacterium can persist in the environment, making it difficult to curb outbreaks. Dysbiosis of the microbiota caused by the use of...

Toxin-antitoxin (TA) systems are widespread on mobile genetic elements and in bacterial chromosomes. In type I TA, synthesis of the toxin protein is prevented by the transcription of an antitoxin RNA. The first type I TA were recently identified in the human enteropathogen Clostridioides difficile. Here we report the characterization of five additi...

Clostridioides difficile is a bacterial pathogen responsible for significant morbidity and mortality across the globe. Current therapies based on broad-spectrum antibiotics have some clinical success, but approximately 30% of patients have relapses, presumably due to the continued perturbation to the gut microbiota. Here, we show that phages can be...

Toxin-antitoxin (TA) systems are widespread on mobile genetic elements as well as in bacterial chromosomes. According to the nature of the antitoxin and its mode of action for toxin inhibition, TA systems are subdivided into different types. The first type I TA modules were recently identified in the human enteropathogen Clostridioides (formerly Cl...

The epidemiology of Clostridioides difficile infection (CDI) has drastically changed since the emergence of the epidemic strain BI/NAP1/027, also known as ribotype 027 (R027). However, the relationship between the infecting C. difficile strain and clinical outcomes is still debated. We hypothesized that certain subpopulations of R027 isolates could...

Bacteriophages (phages) are bacterial viruses that parasitize bacteria. They are highly prevalent in nature, with an estimated 10³¹ viral particles in the whole biosphere, and they outnumber bacteria by at least 10-fold. Hence, phages represent important drivers of bacterial evolution, although our knowledge of the role played by phages in the mamm...

Clostridioides difficile (formerly Clostridium difficile) is a pathogenic bacterium displaying great genetic diversity. A significant proportion of this diversity is due to the presence of integrated prophages. Here, we provide an in-depth analysis of phiCD211, also known as phiCDIF1296T, the largest phage identified in C. difficile so far, with a...

In an effort to understand the mechanisms underlying the high prevalence of gastrointestinal tract disorders in old age, we investigated the expression of intestinal antimicrobial peptides in the terminal small intestine of aged mice. Our results show that old mice have reduced transcript levels of ileal α-defensins and lysozyme, two important type...

The worrying rise of antibiotic resistance in pathogenic bacteria is leading to a renewed interest in bacteriophages as a treatment option. Novel sequencing technologies enable description of an increasing number of phage genomes, a critical piece of information to understand their life cycle, phage-host interactions, and evolution. In this work, w...

Riboswitches recently emerged as possible targets for the development of alternative antimicrobial approaches. Guanine-sensing riboswitches in the bacterial pathogen Clostridioides difficile (formerly known as Clostridium difficile) constitute potential targets based on their involvement in the regulation of basal metabolic control of purine compou...

Bacteriophages are key players in the evolution of most bacteria. Temperate phages have been associated with virulence of some of the deadliest pathogenic bacteria. Among the most notorious cases, the genes encoding the botulinum neurotoxin produced by Clostridium botulinum types C and D and the α-toxin (TcnA) produced by Clostridium novyi are both...

Bacteriophages are the most abundant viruses on earth and display an impressive genetic as well as morphologic diversity. Among those, the most common order of phages is the Caudovirales, whose viral particles packages linear double stranded DNA (dsDNA). In this study we investigated how the information gathered by high throughput sequencing techno...

Infection or inflammation during pregnancy is known to lead to maternal immune activation triggering a fetal inflammatory response syndrome associated with deleterious effects, such as brain injury and neurodevelopmental disabilities. Group B Streptococcus (GBS) - one of the most common bacterium colonizing pregnant women - can be responsible for c...

Group B Streptococcus (GBS) is a commensal bacterium present in the lower genital tract of 15-30% of healthy pregnant women. GBS is the leading cause of chorioamnionitis and cerebral injuries in newborns, occurring most often in the absence of maternofetal pathogen translocation. Despite GBS being the most frequent bacterium colonizing pregnant wom...

Background: Clostridium difficile infection (CDI) is the most common cause of nosocomial infectious diarrhea and may result in severe complications including death. We conducted a prospective study to identify risk factors for complications of CDI (cCDI). Methods: Adult inpatients with confirmed CDI in 10 Canadian hospitals were enrolled and fol...

Clostridium difficile is the cause of most frequently occurring nosocomial diarrhea worldwide. As an enteropathogen, C. difficile must be exposed to multiple exogenous genetic elements in bacteriophage-rich gut communities. CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) systems allow bacteria to adapt to...

Clostridium difficile is an anaerobic Gram-positive bacterium that causes intestinal infections with symptoms ranging from mild diarrhea to fulminant colitis. Cyclic diguanosine monophosphate (c-di-GMP) is a bacterial second messenger that typically regulates the switch from motile, free-living to sessile and multicellular behaviors in Gram-negativ...

Clostridium difficile is one of the most dangerous pathogens in hospital settings. Most strains of C. difficile carry one or more prophages and some of them, like ϕCD38-2 and ϕCD119, can influence the expression of toxin genes. However, little is known about the global host response in the presence of a given prophage. In order to fill this knowled...

Sporulation of Clostridium difficile during infection and persistence of spores within the gut could partly explain treatment failures and recurrence. However, the influence of antibiotics on sporulation is unclear. The objective of our study was to evaluate the impact of ciprofloxacin, metronidazole, piperacillin/tazobactam, tigecycline, and vanco...

The impact of the group B streptococcus (GBS)-induced maternal inflammation on offspring's brain has not yet been investigated despite GBS being one of the most frequent bacteria colonizing or infecting pregnant women. According to our hypothesis GBS-induced maternal immune activation plays a role in offspring perinatal brain damage and subsequent...

Background: Clostridium difficile infection (CDI) is the most common cause of nosocomial diarrhea and often results in severe complications including sepsis, colectomy and death. We conducted a prospective study to identify risk factors for complications or death due to CDI. Methods: Adult inpatients with confirmed CDI in 10 acute care hospitals...

Clostridium difficile causes one of the leading nosocomial infections in developed countries, and therapeutic choices are limited. Some strains of C. difficile produce phage tail-like particles upon induction of the SOS response. These particles have bactericidal activity against other C. difficile strains and can therefore be classified as bacteri...

Prophages contribute to the evolution and virulence of most bacterial pathogens, but their role in Clostridium difficile is unclear. Here we describe the isolation of four Myoviridae phages, ϕMMP01, ϕMMP02, ϕMMP03, and ϕMMP04, that were recovered as free viral particles in the filter-sterilized stool supernatants of patients suffering from C. diffi...

Clostridium difficile strain NAP1/027 (North American pulsed-field gel electrophoresis [PFGE] type 1 and PCR ribotype 027 [R027]) has been associated with recent outbreaks in North America and Europe. It has been associated with more severe disease symptoms, higher mortality rates, and greater risk of relapse. This strain is thought to produce more...

TcdA and TcdB exotoxins are the main virulence factors of Clostridium difficile, one of the most deadly nosocomial pathogens. Recent data suggest that prophages can influence the regulation of toxin expression. Here we present the characterization of φCD38-2, a pac-type temperate Siphoviridae phage that stimulates toxin expression when introduced a...

Accession numbers of genomes of C. difficile strains used in this study. (DOC)

Domain composition and organization of the 3 putative c-di-GMP-signalling proteins encoded by C. difficile strains other than strain 630. Domain composition and organization of the proteins are depicted essentially as in Figure 1. The HD-GYP domain is colored in orange. (TIF)

Analysis of intracellular c-di-GMP by HPLC. 10 µM synthetic c-di-GMP (A), nucleotide extracts from V. cholerae N16961 expressing lacZ from pBAD-TOPO/lacZ/V5-His (negative control) (B), the DGC N-448 from pCD0522-(N-448) (C), or the DGC CD1420 from pCD1420 (D). Spectra of synthetic c-di-GMP (E), and of peaks with corresponding retention times in the...

Predicted and observed activities of the 31 most conserved putative c-di-GMP turn-over proteins. (DOC)