Comparative proteomic analysis of vancomycin-sensitive and vancomycin-intermediate resistant Staphylococcus aureus.

PURPOSE: The extensive use of vancomycin has led to the development of Staphylococcus aureus strains with varying degrees of resistance to vancomycin. The present study aimed to explore the molecular causes of vancomycin resistance by conducting a proteomics analysis of subcellular fractions isolated from vancomycin-intermediate resistant S. aureus (VISA) and vancomycin-sensitive S. aureus (VSSA) strains. METHODS: We conducted proteomics analysis of subcellular fractions isolated from 2 isogenic S. aureus strains: strain 11 (VSSA) and strain 11Y (VISA). We used an integrated quantitative proteomics approach assisted by bioinformatics analysis, and comprehensively investigated the proteome profile. Intensive bioinformatics analysis, including protein annotation, functional classification, functional enrichment, and functional enrichment-based cluster analysis, was used to annotate quantifiable targets. RESULTS: We identified 128 upregulated proteins and 21 downregulated proteins in strain 11Y as compared to strain 11. The largest group of differentially expressed proteins was composed of enzymatic proteins associated with metabolic and catalytic activity, which accounted for 32.1% and 50% of the total proteins, respectively. Some proteins were indispensable parts of the regulatory networks of S. aureus that were altered with vancomycin treatment, and these proteins were related to cell wall metabolism, cell adhesion, proteolysis, and pressure response. CONCLUSION: Our proteomics study revealed regulatory proteins associated with vancomycin resistance in S. aureus. Some of these proteins were involved in the regulation of cell metabolism and function, which provides potential targets for the development of strategies to manage vancomycin resistance in S. aureus.

Clinical and Predictive Value of Computed Tomography Angiography in High-Altitude Pulmonary Hypertension.

Background: High-altitude pulmonary hypertension (HAPH), as the group 3 pulmonary hypertension, has been less studied so far. The limited medical conditions in the high-altitude plateau are responsible for the delay of the clinical management of HAPH. Objectives: This study aims to identify the imaging characteristics of HAPH and explore noninvasive assessment of mean pulmonary arterial pressure (mPAP) based on computed tomography angiography (CTA). Methods: Twenty-five patients with suspected HAPH were enrolled. Right heart catheterization (RHC) and pulmonary angiography were performed. Echocardiography and CTA image data were collected for analysis. A multivariable linear regression model was fit to estimate mPAP (mPAPpredicted). A Bland-Altman plot and pathological analysis were performed to assess the diagnostic accuracy of this model. Results: Patients with HAPH showed slow blood flow and coral signs in lower lobe pulmonary artery in pulmonary arteriography, and presented trend for dilated pulmonary vessels, enlarged right atrium, and compressed left atrium in CTA (P for trend <0.05). The left lower pulmonary artery-bronchus ratio (odds ratio: 1.13) and the ratio of right to left atrial diameter (odds ratio: 1.09) were significantly associated with HAPH, and showed strong correlation with mPAPRHC, respectively (r = 0.821 and r = 0.649, respectively; all P < 0.0001). The mPAPpredicted model using left lower artery-bronchus ratio and ratio of right to left atrial diameter as covariates showed high correlation with mPAPRHC (r = 0.907; P < 0.0001). Patients with predicted HAPH also had the typical pathological changes of pulmonary hypertension. Conclusions: Noninvasive mPAP estimation model based on CTA image data can accurately fit mPAPRHC and is beneficial for the early diagnosis of HAPH.