A study on virulence factors and antimicrobial resistance pattern among enterococci isolated from various clinical specimens from a tertiary care hospital

Background: Enterococci, adult faeces commensal are important nosocomial pathogens. E. faecalis is the most common cause of infection, followed by E. faecium. In the past two decades, they have developed resistance to many commonly used antimicrobial agents. Understanding virulence factors and monitoring antimicrobial resistance among Enterococci is essential for controlling the spread of bacterial resistance and important for epidemiological surveillance within the hospital environment. The aim of the study is to evaluate antibiotic resistance and virulence factors exhibited by Enterococcus sp.Methods: One hundred consecutive isolates of Enterococci isolated from different clinical samples of patients attending AVMC and H, a tertiary care center at Pondicherry in a period of 20 months were included in the study. Enterococcus sp were identified as per standard conventional bacteriologic methods and detected for the production of virulence factors such as Hemolysin production, Gelatinase production. Antimicrobial susceptibility testing was carried out by disc diffusion method and MIC of vancomycin and teicoplanin was determined by E-test strips.Results: Among 100 Enterococcal isolates included in the study, 81% were E. faecalis and 19% were E. faecium which were isolated from urine (44%), Pus (51%) and others specimen (5%, which includes blood 80% and drain tube 20%). In this study, overall 15% of E. faecalis and 1% of E. faecium showed hemolysin production and Gelatinase was produced by 6% of E. faecalis and 4% of E. faecium. Majority of E. faecalis and E. faecium strains isolated in our study, had increased sensitivity were to be exhibited for Linezolid, Vancomycin followed by high level gentamycin and high degree of resistance to penicillin, ciprofloxacin and cotrimoxazole. Analyzing the results of MIC of vancomycin and teicoplanin, 5 isolates were classified phenotypically as VanB phenotype that possess only moderate to high levels of vancomycin resistance and one isolate obtained from drain tube which showed MIC of vancomycin as 120µg/ml and teicoplanin 16µg/ml was grouped into VanA.Conclusions: Though the prevalence of vancomycin resistant Enterococcci (VRE) is very low in our study, yet regular monitoring of vancomycin resistance is very crucial for early detection, treatment, application of preventive and control measures and most importantly to check the spread of virulent multidrug resistant Enterococcus species

Genome wide analysis of gene expression changes in skin from patients with type 2 diabetes

Non-healing chronic ulcers are a serious complication of diabetes and are a major healthcare problem. While a host of treatments have been explored to heal or prevent these ulcers from forming, these treatments have not been found to be consistently effective in clinical trials. An understanding of the changes in gene expression in the skin of diabetic patients may provide insight into the processes and mechanisms that precede the formation of non-healing ulcers. In this study, we investigated genome wide changes in gene expression in skin between patients with type 2 diabetes and non-diabetic patients using next generation sequencing. We compared the gene expression in skin samples taken from 27 patients (13 with type 2 diabetes and 14 non-diabetic). This information may be useful in identifying the causal factors and potential therapeutic targets for the prevention and treatment of diabetic related diseases

Functional genomics reveals serine synthesis is essential in PHGDH-amplified breast cancer

Cancer cells adapt their metabolic processes to drive macromolecular biosynthesis for rapid cell growth and proliferation[superscript 1, 2]. RNA interference (RNAi)-based loss-of-function screening has proven powerful for the identification of new and interesting cancer targets, and recent studies have used this technology in vivo to identify novel tumour suppressor genes[superscript 3]. Here we developed a method for identifying novel cancer targets via negative-selection RNAi screening using a human breast cancer xenograft model at an orthotopic site in the mouse. Using this method, we screened a set of metabolic genes associated with aggressive breast cancer and stemness to identify those required for in vivo tumorigenesis. Among the genes identified, phosphoglycerate dehydrogenase (PHGDH) is in a genomic region of recurrent copy number gain in breast cancer and PHGDH protein levels are elevated in 70% of oestrogen receptor (ER)-negative breast cancers. PHGDH catalyses the first step in the serine biosynthesis pathway, and breast cancer cells with high PHGDH expression have increased serine synthesis flux. Suppression of PHGDH in cell lines with elevated PHGDH expression, but not in those without, causes a strong decrease in cell proliferation and a reduction in serine synthesis. We find that PHGDH suppression does not affect intracellular serine levels, but causes a drop in the levels of α-ketoglutarate, another output of the pathway and a tricarboxylic acid (TCA) cycle intermediate. In cells with high PHGDH expression, the serine synthesis pathway contributes approximately 50% of the total anaplerotic flux of glutamine into the TCA cycle. These results reveal that certain breast cancers are dependent upon increased serine pathway flux caused by PHGDH overexpression and demonstrate the utility of in vivo negative-selection RNAi screens for finding potential anticancer targets.Susan G. Komen Breast Cancer Foundation (Fellowship)Life Sciences Research Foundation (Fellowship)W. M. Keck FoundationDavid H. Koch Cancer Research FundAlexander and Margaret Stewart TrustNational Institutes of Health (U.S.) (Grant CA103866

Left ventricular blood flow kinetic energy after myocardial infarction - insights from 4D flow cardiovascular magnetic resonance

Background: Myocardial infarction (MI) leads to complex changes in left ventricular (LV) haemodynamics that are linked to clinical outcomes. We hypothesize that LV blood flow kinetic energy (KE) is altered in MI and is associated with LV function and infarct characteristics. This study aimed to investigate the intra-cavity LV blood flow KE in controls and MI patients, using cardiovascular magnetic resonance (CMR) four-dimensional (4D) flow assessment. Methods: Forty-eight patients with MI (acute-22; chronic-26) and 20 age/gender-matched healthy controls underwent CMR which included cines and whole-heart 4D flow. Patients also received late gadolinium enhancement imaging for infarct assessment. LV blood flow KE parameters were indexed to LV end-diastolic volume and include: averaged LV, minimal, systolic, diastolic, peak E-wave and peak A-wave KEiEDV. In addition, we investigated the in-plane proportion of LV KE (%) and the time difference (TD) to peak E-wave KE propagation from base to mid-ventricle was computed. Association of LV blood flow KE parameters to LV function and infarct size were investigated in all groups. Results: LV KEiEDV was higher in controls than in MI patients (8.5 ± 3 μJ/ml versus 6.5 ± 3 μJ/ml, P = 0.02). Additionally, systolic, minimal and diastolic peak E-wave KEiEDV were lower in MI (P < 0.05). In logistic-regression analysis, systolic KEiEDV (Beta = − 0.24, P < 0.01) demonstrated the strongest association with the presence of MI. In multiple-regression analysis, infarct size was most strongly associated with in-plane KE (r = 0.5, Beta = 1.1, P < 0.01). In patients with preserved LV ejection fraction (EF), minimal and in-plane KEiEDV were reduced (P < 0.05) and time difference to peak E-wave KE propagation during diastole increased (P < 0.05) when compared to controls with normal EF. Conclusions: Reduction in LV systolic function results in reduction in systolic flow KEiEDV. Infarct size is independently associated with the proportion of in-plane LV KE. Degree of LV impairment is associated with TD of peak E-wave KE. In patient with preserved EF post MI, LV blood flow KE mapping demonstrated significant changes in the in-plane KE, the minimal KEiEDV and the TD. These three blood flow KE parameters may offer novel methods to identify and describe this patient population