Comparative Efficacy of Novel Endolysins in Queso Fresco

Listeria monocytogenes is problematic for the manufacturing, storage, and consumption of ready-to-eat foods. This bacterium may cause listeriosis upon consumption often with deadly complications. Queso Fresco (QF), a pasteurized Hispanic-style fresh cheese (HSFC), has been shown to support the growth of L. monocytogenes. QF is the most widely produced and implicated HSFC in the U.S., representing a significant health hazard to at risk populations such as infants, pregnant women, elderly, and the immunocompromised. The objective of this research project is to evaluate the efficacy of ten novel antimicrobial endolysins in combatting L. monocytogenes contamination in a miniaturized lab-scale queso fresco model over a 28 day shelf life

Caveolin-1 single nucleotide polymorphism in antineutrophil cytoplasmic antibody associated vasculitis

OBJECTIVE: Immunosuppression is cornerstone treatment of antineutrophil cytoplasmic antibody associated vasculitis (AAV) but is later complicated by infection, cancer, cardiovascular and chronic kidney disease. Caveolin-1 is an essential structural protein for small cell membrane invaginations known as caveolae. Its functional role has been associated with these complications. For the first time, caveolin-1 (CAV1) gene variation is studied in AAV. METHODS: CAV1 single nucleotide polymorphism rs4730751 was analysed in genomic DNA from 187 white patients with AAV from Birmingham, United Kingdom. The primary outcome measure was the composite endpoint of time to all-cause mortality or renal replacement therapy. Secondary endpoints included time to all-cause mortality, death from sepsis or vascular disease, cancer and renal replacement therapy. Validation of results was sought from 589 white AAV patients, from two European cohorts. RESULTS: The primary outcome occurred in 41.7% of Birmingham patients. In a multivariate model, non-CC genotype variation at the studied single nucleotide polymorphism was associated with increased risk from: the primary outcome measure [HR 1.86; 95% CI: 1.14-3.04; p=0.013], all-cause mortality [HR:1.83; 95% CI: 1.02-3.27; p=0.042], death from infection [HR:3.71; 95% CI: 1.28-10.77; p=0.016], death from vascular disease [HR:3.13; 95% CI: 1.07-9.10; p=0.037], and cancer [HR:5.55; 95% CI: 1.59-19.31; p=0.007]. In the validation cohort, the primary outcome rate was far lower (10.4%); no association between genotype and the studied endpoints was evident. CONCLUSIONS: The presence of a CC genotype in Birmingham is associated with protection from adverse outcomes of immunosuppression treated AAV. Lack of replication in the European cohort may have resulted from low clinical event rates. These findings are worthy of further study in larger cohorts

ANCA-associated vasculitis is linked to carriage of the Z allele of {alpha}1 antitrypsin and its polymers.

Background Small studies have linked alpha 1 antitrypsin (alpha 1AT) deficiency to patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). Objective To test the validity and the mechanism of this association between alpha 1AT and AAV.Methods The distribution of alpha 1AT deficiency alleles Z and S was compared between 856 White Europeans with AAV and 1505 geographic and ethnically matched healthy controls. Genotyping was performed by allelic discrimination assay. Results were compared between cases and controls using chi(2) tests. The serum and renal biopsies for alpha 1AT polymers were compared using the polymer-specific 2C1 antibody. The role of alpha 1AT polymers in promoting inflammation was investigated by examining their ability to prime neutrophils for ANCA activation as assessed by CD62L shedding, superoxide production and myeloperoxidase degranulation.Results The Z but not the S allele was over-represented in the patients compared with controls (HR=2.25, 95% CI 1.60 to 3.19). Higher concentrations of polymers of alpha 1AT were detected in serum from patients carrying the Z allele than in those not carrying the Z allele (median (IQR) 1.40 (0.91-3.32) mg/dl vs 0.17 (0.06-0.28) mg/dl, p<0.001); polymers of alpha 1AT were also seen in the renal biopsy of a patient with vasculitic glomerulonephritis. Polymers of alpha 1AT primed neutrophils with CD62L shedding and increased superoxide production following ANCA activation. Carriage of the Z allele was not associated with disease severity, survival or relapse.Conclusions The Z but not the S deficiency allele is associated with AAV. Polymers of alpha 1AT are present in the serum and glomeruli of at least some patients with the Z allele, which may promote inflammation through priming of neutrophils

Kaplan-Meier analysis of time to all-cause mortality and renal replacement therapy in the Birmingham (A) and Northern European (B) cohort by genotype of <i>CAV1</i> SNP rs4730751.

<p>The number of patients at risk at separate time points is shown by year of follow-up. Graphic data shown to the last surviving 10% patients. p=0.022 (A) and p=0.427 (B).</p