ABSTRACT
Escherichia coli (E. coli) is a Gram-negative bacterium that belongs to the family Enterobacteriaceae. While E. coli can stay as an innocuous resident in the digestive tract, it can cause a group of symptoms ranging from diarrhea to live threatening complications. Due to the increased rate of antibiotic resistance worldwide, the development of an effective vaccine against E. coli pathotypes is a major health priority. In this study, a reverse vaccinology approach along with immunoinformatics has been applied for the detection of potential antigens to develop an effective vaccine. Based on our screening of 5,155 proteins, we identified lipopolysaccharide assembly protein (LptD) and outer membrane protein assembly factor (BamA) as vaccine candidates for the current study. The conservancy of these proteins in the main E. coli pathotypes was assessed through BLASTp to make sure that the designed vaccine will be protective against major E. coli pathotypes. The multitope vaccine was constructed using cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and B cell lymphocyte (BCL) epitopes with suitable linkers and adjuvant. Following that, it was analyzed computationally where it was found to be antigenic, soluble, stable, and non-allergen. Additionally, the adopted docking study, as well as all-atom molecular dynamics simulation, illustrated the promising predicted affinity and free binding energy of this constructed vaccine against the human Toll-like receptor-4 (hTLR-4) dimeric state. In this regard, wet lab studies are required to prove the efficacy of the potential vaccine construct that demonstrated promising results through computational validation.
ABSTRACT
BACKGROUND: Sepsis-induced diaphragmatic dysfunction is one of the main risk factors of failure to liberate patients from mechanical ventilation. Several studies addressed diaphragmatic ultrasound as a valuable tool in the assessment of diaphragmatic function during liberation from mechanical ventilation in different populations. However, none of these studies examined the use of diaphragmatic ultrasound to predict failure of liberation from mechanical ventilation in subjects with sepsis METHODS: A prospective observational study was done with subjects on mechanical ventilation and with abdominal sepsis. The diaphragmatic thickening fraction, diaphragmatic excursion, and rapid shallow breathing index were assessed 30 min after a spontaneous breathing trial RESULTS: Thirty subjects were enrolled in the study. Seventeen subjects were successfully extubated (56.6%), whereas extubation failed in 13 subjects (43.4%). The time to the first liberation attempt was significantly shorter in the liberation-success group 2.3 (0.7) d compared with the liberation-failure group 5.8 (4.7) d; P = .02. The optimum cutoff value of diaphragmatic thickening fraction for predicting liberation success was ≥30.7%, with a sensitivity of 94.1% and a specificity of 100%. The area under the curve was 0.977. Although diaphragmatic excursion of ≥10.4 mm had a sensitivity of 94% and a specificity of 85% for predicting liberation success, with an area under the curve of 0.85. A rapid shallow breathing index of ≤44 had a specificity of 100% and a sensitivity of 76%; the area under the curve was 0.9. CONCLUSIONS: Diaphragmatic ultrasound indices, namely diaphragmatic thickening fraction and diaphragmatic excursion, could be useful parameters for assessment of success of liberation in patients on mechanical ventilation with abdominal sepsis. (ClinicalTrials.gov registration NCT03094299.).
