| 1. |
- Chowdhury, Sounak, et al.
(author)
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Streptococcus pyogenes Forms Serotype- and Local Environment-Dependent Interspecies Protein Complexes
- 2021
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In: mSystems. - 2379-5077. ; 6:5, s. 1-19
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Journal article (peer-reviewed)abstract
- Streptococcus pyogenes is known to cause both mucosal and systemic infections in humans. In this study, we used a combination of quantitative and structural mass spectrometry techniques to determine the composition and structure of the interaction network formed between human plasma proteins and the surfaces of different S. pyogenes serotypes. Quantitative network analysis revealed that S. pyogenes forms serotype-specific interaction networks that are highly dependent on the domain arrangement of the surface-attached M protein. Subsequent structural mass spectrometry analysis and computational modeling of one of the M proteins, M28, revealed that the network structure changes across different host microenvironments. We report that M28 binds secretory IgA via two separate binding sites with high affinity in saliva. During vascular leakage mimicked by increasing plasma concentrations in saliva, the binding of secretory IgA was replaced by the binding of monomeric IgA and C4b-binding protein (C4BP). This indicates that an upsurge of C4BP in the local microenvironment due to damage to the mucosal membrane drives the binding of C4BP and monomeric IgA to M28. These results suggest that S. pyogenes has evolved to form microenvironment-dependent host-pathogen protein complexes to combat human immune surveillance during both mucosal and systemic infections. IMPORTANCE Streptococcus pyogenes (group A Streptococcus [GAS]), is a human-specific Gram-positive bacterium. Each year, the bacterium affects 700 million people globally, leading to 160,000 deaths. The clinical manifestations of S. pyogenes are diverse, ranging from mild and common infections like tonsillitis and impetigo to life-threatening systemic conditions such as sepsis and necrotizing fasciitis. S. pyogenes expresses multiple virulence factors on its surface to localize and initiate infections in humans. Among all these expressed virulence factors, the M protein is the most important antigen. In this study, we perform an in-depth characterization of the human protein interactions formed around one of the foremost human pathogens. This strategy allowed us to decipher the protein interaction networks around different S. pyogenes strains on a global scale and to compare and visualize how such interactions are mediated by M proteins.
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| 2. |
- Isaksson, Sofia Sterner, et al.
(author)
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The effect of carbohydrate intake on glycaemic control in individuals with type 1 diabetes: a randomised, open-label, crossover trial
- 2024
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In: LANCET REGIONAL HEALTH-EUROPE. - 2666-7762. ; 37
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Journal article (peer-reviewed)abstract
- Background Few studies have examined the effects of lower carbohydrate diets on glucose control in persons with type 1 diabetes (T1D). The objective of the study was to investigate whether a moderate carbohydrate diet improves glucose control in persons with T1D. Methods A randomised, multicentre, open -label, crossover trial over 12 weeks. There were 69 individuals assessed for eligibility, 54 adults with T1D and HbA1c >= 58 mmol/mol (7.5%) were randomised. Interventions were moderate carbohydrate diet versus traditional diet (30 vs 50% of total energy from carbohydrates) over four weeks, with a four -week wash -out period between treatments. Masked continuous glucose monitoring was used to evaluate effects on glucose control. The primary endpoint was the difference in mean glucose levels between the last 14 days of each diet phase. Findings 50 individuals were included in the full analysis set with a mean baseline HbA1c of 69 mmol/mol (8.4%), BMI 29 kg/m2, age of 48 years, and 50% were female. The difference in mean glucose levels between moderate carbohydrate and traditional diet was -0.6 mmol/L, 95% CI -0.9 to -0.3, p < 0.001. Time in range increased during moderate carbohydrate diet by 4.7% (68 min/24 h) (95% CI 1.3 to 8.0), p = 0.008. Time above range (>10 mmol/L) decreased by 5.9% (85 min/24 h), 95% CI -9.6 to -2.2, p = 0.003. There were no significant differences in the standard deviation of glucose levels (95% CI -0.3 to 0.0 mmol/L, p = 0.15) or hypoglycaemia in the range <3.9 mmol/ L (95% CI -0.4 to 2.9%, p = 0.13) and <3.0 mmol/L (95% CI -0.4 to 1.6%, p = 0.26). Four participants withdrew, none because of adverse events. There were no serious adverse events including severe hypoglycaemia and ketoacidosis. Mean ketone levels were 0.17 (SD 0.14) mmol/L during traditional and 0.18 (SD 0.13) mmol/L during moderate carbohydrate diet (p = 0.02). Interpretation A moderate carbohydrate diet is associated with decreases in mean glucose levels and time above range and increases in time in range without increased risk of hypoglycaemia or ketoacidosis compared with a traditional diet in individuals with T1D. Funding The Healthcare Board, Region Vastra Gotaland, The Dr P Hakansson Foundation and the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement [ALFGBG966173].
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| 3. |
- Tajudin, Asilah Ahmad, et al.
(author)
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Maldi-target integrated microfluidic PSA assay
- 2009
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In: Proceedings of Conference, MicroTAS 2009 - The 13th International Conference on Miniaturized Systems for Chemistry and Life Sciences. - 9780979806421 ; , s. 1064-1066
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Conference paper (peer-reviewed)abstract
- An Integrated Selective Enrichment Target (ISET), microfabricated for efficient on-bead enzymatic digestion of proteins compatible for a direct interface with matrix-assisted laser desorption /ionization mass spectrometry (MALDI MS) is presented.
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