Browsing by Author "Surette, Michael G."
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Item Open Access Antibiotic resistance in swarming salmonella(2008) Apel, Dmitry; Surette, Michael G.Item Open Access Antibiotic tolerance in salmonella typhirmurium as an emergent property of induced aggregate formation by altered environmental viscosity and shear stress(2010) Happe, Jennifer S; Surette, Michael G.; Martinuzzi, RobertItem Open Access Assessment of virulence diversity of methicillin-resistant Staphylococcus aureus strains with a Drosophila melanogaster infection model(BioMed Central, 2012-11-23) Zhang, Kunyan; Wu, Kaiyu; Conly, John; Surette, Michael G.; Sibley, Christopher; Elsayed, SameerItem Open Access Clinical epidemiology and impact of Haemophilus influenzae airway infections in adults with cystic fibrosis(2024-10-27) Weyant, R. Benson; Waddell, Barbara J.; Acosta, Nicole; Izydorczyk, Conrad; Conly, John M.; Church, Deirdre L.; Surette, Michael G.; Rabin, Harvey R.; Thornton, Christina S.; Parkins, Michael D.Abstract Background Haemophilus influenzae is prevalent within the airways of persons with cystic fibrosis (pwCF). H. influenzae is often associated with pulmonary exacerbations (PEx) in pediatric cohorts, but in adults, studies have yielded conflicting reports around the impact(s) on clinical outcomes such as lung function decline. Accordingly, we sought to discern the prevalence, natural history, and clinical impact of H. influenzae in adult pwCF. Methods This single-centre retrospective cohort study reviewed all adult pwCF with H. influenzae sputum cultures between 2002 and 2016. From this cohort, persistently infected subjects (defined as: ≥2 samples with the same pulsotype and > 50% sputum culture-positive for H. influenzae in each year) were matched (1:2) to controls without H. influenzae. Demographic and clinical status (baseline health or during periods of PEx) were obtained at each visit that H. influenzae was cultured. Yearly biobank isolates were typed using pulsed-field gel electrophoresis (PFGE) to assess relatedness. Results Over the study period, 30% (n = 70/240) of pwCF were culture positive for H. influenzae, of which 38 (54%) were culture-positive on multiple occasions and 12 (17%) had persistent infection. One hundred and thirty-seven isolates underwent PFGE, with 94 unique pulsotypes identified. Two (1.5%) were serotype f with the rest non-typeable (98.5%). H. influenzae isolation was associated with an increased risk of PEx (RR = 1.61 [1.14–2.27], p = 0.006), however, this association was lost when we excluded those who irregularly produced sputum (i.e. only during a PEx). Annual lung function decline did not differ across cohorts. Conclusions Isolation of H. influenzae was common amongst adult pwCF but often transient. H. influenzae infection was not associated with acute PEx or chronic lung function decline.Item Open Access Construction and characterization of a salmonella enterica serovar typhimurium random promoter library for gene expression profiling(2007) Bjarnason, Jaime Lynn; Surette, Michael G.Item Open Access Exploring the Effects of Inhaled Antibiotics on the Cystic Fibrosis Lung Microbiome and Pseudomonas aeruginosa Population Diversity and their Clinical Implications(2020-01-20) Heirali, Alya; Parkins, Michael D.; Storey, Douglas G.; van Marle, Guido; Surette, Michael G.The CF lung microbiome is composed of a diverse group of microorganisms. Where the constituents of the microbiome originate from remains poorly understood. The work presented herein shows that the home environment may serve as a reservoir for infection in patients with CF. Researchers have demonstrated that the CF lung microbial communities are dynamic and complex. As patients age and disease progression occurs the diversity of organisms colonizing the lower airways generally decreases and patients become dominated by organisms such as Pseudomonas aeruginosa. Several studies have attempted to increase our understanding of the shifts in the microbial communities prior to pulmonary exacerbations. However, there is a tremendous knowledge gap on how the microbiome changes through chronic suppressive inhaled antibiotics used by the majority of CF patients in Canada. Accordingly, we sought to investigate how inhaled aztreonam and tobramycin affect the CF lung microbiome and whether the microbiome can be used as a tool to predict patient response. We showed that the lung microbiome is relatively fixed in adults with CF despite potent inhaled antibacterial therapy. The relative abundance of Staphylococcus was associated with response in all three studies assessing the effects of inhaled antibiotics on the lung microbiome. Specifically, a higher abundance of Staphylococcus at baseline was associated with non-response to inhaled aztreonam and response to inhaled tobramycin – mirroring expected antibacterial activity and suggesting a potential biomarker for treatment response. Keywords: lung microbiome, cystic fibrosis, inhaled antibiotics, Staphylococcus, P. aeruginosa, biomarkerItem Open Access Gene expression profiling in enterohemorrhagic escherichia coli(2004) Southward, Carolyn Marie; Surette, Michael G.The pathogen Enterohemorrhagic Escherichia coli (EHEC) is a continuing problem in outbreaks associated with contaminated food and water. This study describes the development of a novel high throughput method for monitoring global gene expression in EHEC. The random promoter library is based on a promoter trap method and three reporters lux, gfp and lacZ, were compared for efficacy. The lux reporter system was found to be the best candidate. Random promoter library construction methods were optimized using a partial E. coli MG 1655 library. Subsequently, an EHEC random promoter library was constructed and characterized by assaying gene expression from 3,840 clones under many conditions. Unique expression profiles were observed, the distribution of cloned fragments was random and over-coverage of the genome was indicated by redundancy in the sequencing results. Hierarchical clustering was used to analyze the gene expression data. Co-clustering clones with response profiles unique to certain groups of assay conditions were characterized and sequenced although the results illustrated the difficulties associated with cluster analysis. In contrast, clusters associated with the LEE promoters were well defined and sequence results were classified into groups based on putative function. Gene products associated with response to different cell stresses were represented. Cell wall modifying enzymes were also identified as was miaA, required for tRNA modification and virulence in Shigella. This dataset, including expression profiles in many conditions and sequence information, is a valuable tool and resource for understanding EHEC gene regulation.Item Open Access Integration of transcriptional inputs at promoters of the arabinose catabolic pathway(BioMed Central, 2010-06-02) Davidson, Carla J.; Narang, Atul; Surette, Michael G.Item Open Access Phenotypic and genotypic characteristics of respiratory isolates of the streptococcus milleri group from patients with cystic fibrosis(2012) Grinwis, Margot E.; Surette, Michael G.; Schryvers, Anthony B.Item Open Access Physiological differentiation in swarming salmonella(2004) Kim, Wook; Surette, Michael G.Swarming behaviour in bacteria has been traditionally described as a surface motility phenotype observed on laboratory media. Swarming motility is a collective behaviour of groups of bacterial cells, and unlike the classic swimming motility in broth, vegetative cells must first differentiate into elongated and hyperflagellated swarmer cells. The extent of the morphological changes associated with swarmer differentiation can vary significantly between different organisms. Recent studies indicate that swarmer differentiation represents much more than a motility phenotype, as several clinically important attributes are co-regulated with swarming. In this work, I demonstrate that swarmer differentiation in Salmonella enterica serovar Typhimurium is coupled to elevated resistance to a wide variety of structurally and functionally distinct classes of antibiotics. One mechanism of resistance was directly attributed to the up-regulation of the pmrHFIJKLM operon, and evidence was presented that other mechanisms are likely associated. Adaptive antibiotic resistance in the absence of overt selection suggests that swarmer differentiation may reflect the organism's adaptation to the host environment; not due to antibiotic use, but to the role of host-derived cationic peptides and resident microflora-derived colicins and toxic metabolites that shape the intestinal ecosystem. Proteomic analyses revealed that migrating swarmer cells are metabolically differentiated compared to the vegetative swimmer cells grown in the same nutrient environment. Furthermore, once the cells have differentiated, the swarmers remain in this physiological state under conditions that do not promote the initial differentiation. The permeability of the swarmers' outer membrane was predicted to be relatively reduced, which in part accounts for the multiple antibiotic resistance phenotype. Moreover, the bacterium's capacity to override some of the classic paradigms of metabolic regulation, established in aqueous environments, represents a unique physiological response by the pathogen that may be advantageous in polymicrobial environments such as the host. In addition, cellcell signalling systems were differentially regulated, suggesting that the differentiated cells are also primed to respond to the presence of other organisms and its own increasing population. An experimental model system was developed to measure spatiotemporal gene expression patterns to study gene regulation in the context of transitions between cellular states.Item Open Access Population dynamics and adaptation of pseudomonas aeruginose during chronic lung infection in cystic fibrosis(2010) Norgaard-Gron, Jens Christian; Surette, Michael G.Pseudomonas aeruginosa is the most frequently isolated organism from patients with cystic fibrosis. Colonization occurs in early childhood and persists throughout the lifetime of patients. During chronic airway infection, P. aeruginosa is generally thought to evolve into a chronic phenotype characterized by acquisition of a number of mutations that results in loss of virulence factors required for acute infection. However, P. aeruginosa cultured from sputum exhibits a wide range of colony morphologies and suggests that P. aeruginosa in chronic airway infection has an unexplored level of diversity. To examine the population dynamics of P. aeruginosa in CF airways, we monitored morphotypes isolated during periods of pulmonary exacerbation in four CF adult patients with quantitative and quantitative microbiology. Phenotypic profiling was carried out for P. aeruginosa virulence factors generally considered to be lost during chronic infection. Results from this study indicate that P. aeruginosa CF population is highly diverse and virulence factors are still present in chronic infection.Item Open Access Regulation of autoinducer-2 production in salmonella enterica serovar typhimurium(2003) Beeston, Anne Louise; Surette, Michael G.Item Open Access Regulation of multicellular behviours in salmonella(2010) Turnbull, Amy L.; Surette, Michael G.Item Open Access The polymicrobial nature of airway infections in cystic fibrosis(2010) Sibley, Christopher D.; Surette, Michael G.