Browsing by Author "Nguyen, Austin"

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    Critically Re-evaluating Carbohydrate Metabolism in Pseudomonas aeruginosa
    (2019-09-19) Nguyen, Austin; Lewis, Ian A.; Storey, Douglas G.; Harrison, Joe J.; DeVinney, Rebekah
    Several studies have linked carbon metabolism to a variety of different factors in P. aeruginosa. For example, the production of gluconate and 2-ketogluconate has been linked to exotoxin production, antibiotic resistance, and iron acquisition. However, glucose catabolism is known to participate in P. aeruginosa aerobic respiration. We hypothesize that, rather than factors such as iron acquisition, P. aeruginosa gluconate and 2-ketogluconate production is instead driven by the energetic needs of the cell. We developed a targeted LC-MS method and analyzed P. aeruginosa glucose metabolism production in a variety of limiting conditions. From our data, we made a model of P. aeruginosa metabolism where energy production is decoupled from biomass generation via periplasmic glucose oxidation. This model introduces a regulatory mechanism of carbon catabolism that explains the production of gluconate and 2-ketogluconate through cellular energy demands.
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    Group B streptococcus (GBS) is an important pathogen in human disease- but what about in cystic fibrosis?
    (2017-10-02) Skolnik, Kate; Nguyen, Austin; Thornton, Christina S; Waddell, Barbara; Williamson, Tyler; Rabin, Harvey R; Parkins, Michael D
    Abstract Background Group B Streptococcus (GBS) is a common commensal capable of causing severe invasive infections. Most GBS infections occur in neonates (often as pneumonia). GBS can also cause infection in adults with diabetes and other immunological impairments but rarely leads to pneumonia in adults. GBS has occasionally been found in the sputum of Cystic Fibrosis (CF) patients, an inherited condition known for progressive lung disease. However, the epidemiology and clinical significance of GBS in CF are not understood. Methods We retrospectively reviewed a large single-centre adult CF population with an associated comprehensive, prospectively collected bacterial biobank beginning in 1978. We identified all individuals with GBS isolated from their sputum on at least one occasion. The primary outcome was risk of pulmonary exacerbation (PEx) at the time of the first GBS isolate compared to the preceding visit. Secondary outcomes included determining: prevalence of GBS infection in a CF population, whether GBS infections where transient or persistent, whether GBS strains were shared among patients, change in % predicted FEV1 at the time of GBS isolate compared to the preceding visit, PEx frequency after the first GBS isolate, change in % predicted FEV1 after the first GBS isolate, and complications of GBS infection. Results GBS was uncommon, infecting 3.5% (11/318) adults within our cohort. Only three individuals developed persistent GBS infection, all lasting > 12 months. There were no shared GBS strains among patients. PEx risk was not increased at initial GBS isolation (RR 5.0, CI 0.69–36.1, p=0.10). In the two years preceding initial GBS isolation compared to the two following years, there was no difference in PEx frequency (median 2, range 0–4 vs 1, range 0 to 5, respectively, p=0.42) or lung function decline, as measured by % predicted FEV1, (median −1.0%, range −19 to 7% vs median −6.0%, range −18 to 22%, p=0.86). There were no invasive GBS infections. Conclusion In adults with CF, GBS is uncommon and is generally a transient colonizer of the lower airways. Despite the presence of structural lung disease and impaired innate immunity in CF, incident GBS infection did not increase PEx risk, PEx frequency, rate of lung function decline, or other adverse clinical outcomes.