Browsing by Author "Buret, Andre G"

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    Biofilm-derived Small Molecules Released from Mixed-species Cultures of Fusobacterium necrophorum and Porphyromonas levii Inhibit Bovine Neutrophil Functional Responses
    (2022-05-06) Lockhart, Joey Scott; Morck, Douglas Walter; Buret, Andre G; Harrison, Joe Jonathan; Hirota, Simon; De Buck, Jeroen Marc Daniel; James, Garth Alan
    Bacterial biofilms are surface adhered communities of microorganisms encased in a protective polysaccharide layer. These resilient structures present significant challenges for effective host immune cell clearance or clinical interventions, frequently resulting in recurrent infections in cattle, humans, and other animals. Fusobacterium necrophorum and Porphyromonas levii are two species of anaerobic, Gram-negative, opportunistic pathogens that have been described as etiological agents in a variety of necrotic, recalcitrant infections. With antimicrobial resistance on the rise, it is important to elucidate the reasons why biofilm-associated infections are so difficult to eradicate. Neutrophils are critical first responder cells that are recruited to a site of bacterial colonization to initiate the inflammatory response. In this dissertation research, an in vitro system for the growth of mixed-species anaerobic biofilms was employed to investigate bovine neutrophil responses to biofilm bacteria compared to planktonic cultures of the same two species. Neutrophils exposed to biofilm soluble factors generated reduced oxidative and chemotactic responses compared to neutrophils exposed to planktonic bacteria-generated products. Ultra-filtration revealed that a <3kDa molecule is differentially expressed in the bacterial supernatants and allows biofilm-bacteria to inhibit neutrophil responses. Intensive heat, protease, lipase, or nuclease treatment of the <3kDa fractions prior to exposure to bovine neutrophils did not alter the differential oxidative responses. This led to an investigation of small, heat stable compounds and our results suggest that the accumulation of protoporphyrin IX in the biofilm mode of growth attenuates neutrophil chemotaxis and reactive oxygen species production. This work provides evidence for a mechanism by which these biofilm bacteria evade host immune cells and understanding such mechanisms is important to reduce the persistent inflammation and negative clinical outcomes associated with chronic biofilm-mediated disease.
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    Erratum to: The nasopharyngeal microbiota of beef cattle before and after transport to a feedlot
    (2017-04-20) Holman, Devin B; Timsit, Edouard; Amat, Samat; Abbott, D. W; Buret, Andre G; Alexander, Trevor W
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    Infection control in ERCP using a duodenoscope with a disposable cap (ICECAP): rationale for and design of a randomized controlled trial
    (2020-03-12) Forbes, Nauzer; Elmunzer, B. J; Allain, Thibault; Chau, Millie; Koury, Hannah F; Bass, Sydney; Belletrutti, Paul J; Cole, Martin J; Gonzalez-Moreno, Emmanuel; Kayal, Ahmed; Kumar, Puja; Mohamed, Rachid; Turbide, Christian; Buret, Andre G; Heitman, Steven J
    Abstract Background Endoscopic retrograde cholangio-pancreatography (ERCP) is commonly performed in the management of pancreatic and biliary disease. Duodenoscopes are specialized endoscopes used to perform ERCP, and inherent to their design, a high rate of persistent bacterial contamination exists even after automated reprocessing and disinfection. Consequently, in recent years, ERCP has been associated with infection transmission, leading to several fatal patient outbreaks. Due to increasing fears over widespread future duodenoscope-related outbreaks, regulatory bodies have called for alterations in the design of duodenoscopes. A duodenoscope has recently been developed that employs a disposable cap. This novel design theoretically eliminates the mechanism behind persistent bacterial contamination and infection transmission. However, there are no data demonstrating persistent bacterial contamination rates, technical success rates, or clinical outcomes associated with these duodenoscopes. Methods A parallel arm randomized controlled trial will be performed for which 520 patients will be recruited. The study population will consist of consecutive patients undergoing ERCP procedures for any indication at a high-volume tertiary care centre in Calgary, Alberta, Canada. Patients will be randomized to an intervention group, that will undergo ERCP with a novel duodenoscope with disposable cap, or to a control group who will undergo ERCP with a traditional duodenoscope. Co-primary outcomes will include persistent bacterial contamination rates (post automated reprocessing) and ERCP technical success rates. Secondary outcomes include clinical success rates, overall and specific early and late adverse event rates, 30-day mortality and healthcare utilization rates, procedure and reprocessing times, and ease of device use. Discussion The ICECAP trial will answer important questions regarding the use of a novel duodenoscope with disposable cap. Specifically, persistent bacterial contamination, technical performance, and relevant clinical outcomes will be assessed. Given the mortality and morbidity burden associated with ERCP-related infectious outbreaks, the results of this study have the capacity to be impactful at an international level. Trial registration This trial was registered on clinicaltrials.gov (NCT04040504) on July 31, 2019.
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    Pathobiont release from dysbiotic gut microbiota biofilms in intestinal inflammatory diseases: a role for iron?
    (2019-01-03) Buret, Andre G; Motta, Jean-Paul; Allain, Thibault; Ferraz, Jose; Wallace, John L
    Abstract Gut microbiota interacting with an intact mucosal surface are key to the maintenance of homeostasis and health. This review discusses the current state of knowledge of the biofilm mode of growth of these microbiota communities, and how in turn their disruptions may cause disease. Beyond alterations of relative microbial abundance and diversity, the aim of the review is to focus on the disruptions of the microbiota biofilm structure and function, the dispersion of commensal bacteria, and the mechanisms whereby these dispersed commensals may become pathobionts. Recent findings have linked iron acquisition to the expression of virulence factors in gut commensals that have become pathobionts. Causal studies are emerging, and mechanisms common to enteropathogen-induced disruptions, as well as those reported for Inflammatory Bowel Disease and colo-rectal cancer are used as examples to illustrate the great translational potential of such research. These new observations shed new light on our attempts to develop new therapies that are able to protect and restore gut microbiota homeostasis in the many disease conditions that have been linked to microbiota dysbiosis.
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    The nasopharyngeal microbiota of beef cattle before and after transport to a feedlot
    (2017-03-22) Holman, Devin B; Timsit, Edouard; Amat, Samat; Abbott, D. W; Buret, Andre G; Alexander, Trevor W
    Abstract Background The nasopharyngeal (NP) microbiota plays an important role in bovine health, comprising a rich and diverse microbial community. The nasopharynx is also the niche for potentially pathogenic agents which are associated with bovine respiratory disease (BRD), a serious and costly illness in feedlot cattle. We used 14 beef heifers from a closed and disease-free herd to assess the dynamics of the NP microbiota of cattle that are transported to a feedlot. Cattle were sampled prior to transport to the feedlot (day 0) and at days 2, 7, and 14. Results The structure of the NP microbiota changed significantly over the course of the study, with the largest shift occurring between day 0 (prior to transport) and day 2 (Pā€‰<ā€‰0.001). Phylogenetic diversity and richness increased following feedlot placement (day 2; Pā€‰<ā€‰0.05). The genera Pasteurella, Bacillus, and Proteus were enriched at day 0, Streptococcus and Acinetobacter at day 2, Bifidobacterium at day 7, and Mycoplasma at day 14. The functional potential of the NP microbiota was assessed using PICRUSt, revealing that replication and repair, as well as translation pathways, were more relatively abundant in day 14 samples. These differences were driven mostly by Mycoplasma. Although eight cattle were culture-positive for the BRD-associated bacterium Pasteurella multocida at one or more sampling times, none were culture-positive for Mannheimia haemolytica or Histophilus somni. Conclusions This study investigated the effect that feedlot placement has on the NP microbiota of beef cattle over a 14-d period. Within two days of transport to the feedlot, the NP microbiota changed significantly, increasing in both phylogenetic diversity and richness. These results demonstrate that there is an abrupt shift in the NP microbiota of cattle after transportation to a feedlot. This may have importance for understanding why cattle are most susceptible to BRD after feedlot placement.