Fructose-enabled killing of antibiotic-resistant Salmonella enteritidis by gentamicin: Insight from reprogramming metabolomics.

Salmonella enterica is a food-borne pathogen that poses a severe threat to both poultry production and human health. Antibiotics are critical for the initial treatment of bacterial infections. However, the overuse and misuse of antibiotics results in the rapid evolution of antibiotic-resistant bacteria, and the discovery and development of new antibiotics are declining. Therefore, understanding antibiotic resistance mechanisms and developing novel control measures are essential. In the present study, GC-MS-based metabolomics analysis was performed to determine the metabolic profile of gentamicin sensitive (SE-S) and resistant (SE-R) S. enterica. Fructose was identified as a crucial biomarker. Further analysis demonstrated a global depressed central carbon metabolism and energy metabolism in SE-R. The decrease in the pyruvate cycle reduces the production of NADH and ATP, causing a decrease in membrane potential, which contributes to gentamicin resistance. Exogenous fructose potentiated the effectiveness of gentamicin in killing SE-R by promoting the pyruvate cycle, NADH, ATP and membrane potential, thereby increasing gentamicin intake. Further, fructose plus gentamicin improved the survival rate of chicken infected with gentamicin-resistant Salmonella in vivo. Given that metabolite structures are conserved across species, fructose identified from bacteria could be used as a biomarker for breeding disease-resistant phenotypes in chicken. Therefore, a novel strategy is proposed for fighting against antibiotic-resistant S. enterica, including exploring molecules suppressed by antibiotics and providing a new approach to find pathogen targets for disease resistance in chicken breeding.

Serum cardiac troponin elevation predicts mortality in patients with pulmonary hypertension: A meta-analysis of eight cohort studies.

OBJECTIVE: To determine the association of serum cardiac troponin (cTn) with the mortality of pulmonary hypertension (PH) patients via a meta-analysis. DATE SOURCE: We searched PubMed and EMBASE from inception to October 25, 2017. STUDY SELECTION: The reference lists of the retrieved articles were also consulted. The Q test and I2 test were used for to assess heterogeneity. The relationship between cTn elevation and mortality was analysed. Studies were stratified according to type of troponin (cTnT vs cTnI), region (Europe vs America) and follow-up length (≤3 years vs >3 years). RESULTS: Eight studies with 739 patients were included in the meta-analysis. Cardiac troponin elevation ranged from 14.3% to 94.5%. Overall, 48.8% (39/80) of patients with elevated cTn died compared to 18.6% (45/242) of patients with normal cTn levels. These findings showed cTn elevation was significantly related to an increased mortality risk in PH patients [hazard ratio (HR) = 3.05, 95% confidence interval (95% CI) = 2.16-4.32, I2  = 24.9%]. cTnI was better at predicting mortality than cTnT (HR = 3.37, 95%CI = 2.05-5.55 vs HR = 2.80, 95%CI = 1.97-3.98, respectively). American populations had increased mortality compared to European populations (HR = 4.23, 95%CI = 2.29-7.80 vs HR = 2.70, 95% CI = 1.95-3.74, respectively). This finding was independent of the follow-up length of the studies (≤3 years: HR = 2.36, 95%CI = 1.65-3.38; >3 years: HR = 4.55, 95%CI = 2.80-7.39). CONCLUSIONS: Although different studies detected the expression cTnT or cTnI by various methods, the mortality in the cTn-positive group was higher than that in the cTn-negative group. Serum cTn elevation emerged as an independent predictor of increased risk of mortality in PH patients.