The Antioxidant Enzyme Methionine Sulfoxide Reductase A (MsrA) Interacts with Jab1/CSN5 and Regulates Its Function

This work is licensed under a Creative Commons Attribution 4.0 International License.Methionine sulfoxide (MetO) is an oxidative posttranslational modification that primarily occurs under oxidative stress conditions, leading to alteration of protein structure and function. This modification is regulated by MetO reduction through the evolutionarily conserved methionine sulfoxide reductase (Msr) system. The Msr type A enzyme (MsrA) plays an important role as a cellular antioxidant and promotes cell survival. The ubiquitin- (Ub) like neddylation pathway, which is controlled by the c-Jun activation domain-binding protein-1 (Jab1), also affects cell survival. Jab1 negatively regulates expression of the cell cycle inhibitor cyclin-dependent kinase inhibitor 1B (P27) through binding and targeting P27 for ubiquitination and degradation. Here we report the finding that MsrA interacts with Jab1 and enhances Jab1′s deneddylase activity (removal of Nedd8). In turn, an increase is observed in the level of deneddylated Cullin-1 (Cul-1, a component of E3 Ub ligase complexes). Furthermore, the action of MsrA increases the binding affinity of Jab1 to P27, while MsrA ablation causes a dramatic increase in P27 expression. Thus, an interaction between MsrA and Jab1 is proposed to have a positive effect on the function of Jab1 and to serve as a means to regulate cellular resistance to oxidative stress and to enhance cell survival.Hedwig Miller Fund for Aging Research of the University of KansasU.S. Department of Energy, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences and Biosciences, Physical Biosciences Program (DOE DE-FG02-05ER15650)NIH R01 GM5749

Multidrug resistant Kluyvera ascorbata septicemia in an adult patient: a case report

<p>Abstract</p> <p>Introduction</p> <p><it>Kluyvera ascorbata </it>has become increasingly significant due to its potential to cause a wide range of infections, as well as its ability to transfer gene encoding for CTX-M- type extended spectrum B-lactamases (ESBLs) to other Enterobacteriaceae.</p> <p>Case presentation</p> <p>We report the case of a 64-year-old African-American male diagnosed with severe sepsis due to a multidrug resistant <it>Kluyvera ascorbata</it>, which was isolated from his blood. He was treated with meropenem and had a favorable outcome.</p> <p>Conclusion</p> <p>To the best of our knowledge, this is the first case report of a multidrug resistant <it>Kluyvera ascorbata </it>isolated from the blood in an adult patient with sepsis.</p

Fulminant Amebic Colitis after Corticosteroid Therapy: A Systematic Review

<div><p>Background</p><p>Amebic colitis, caused by intestinal infection with the parasite, <i>Entamoeba histolytica</i>, is a common cause of diarrhea worldwide. Fulminant amebic colitis is the most devastating complication of this infection, associated with both high mortality and morbidity. We conducted a review of the English literature to describe cases of fulminant amebic colitis associated with exposure to corticosteroid medications in order to identify the risk factors for poor outcome and determine difficulties in diagnosis and treatment.</p><p>Methodology and Principal Findings</p><p>Articles reporting severe and fulminant forms of amebic colitis between 1991 and 2016 were collected. 525 records were screened to identify 24 cases for qualitative analysis associated with corticosteroid use. Cases arose from areas of high endemicity or travel to such areas. Most cases (14 of 24, 58%) were given corticosteroids for initially misdiagnosed colitis, mainly inflammatory bowel, resulting in rapid progression of disease. Nearly half of all cases underwent surgical intervention, and 25% of cases died, despite all patients eventually receiving treatment with metronidazole. The odds of death did not differ significantly by prior misdiagnosis, co-morbidities, bowel perforation or need for surgery.</p><p>Conclusions and Significance</p><p>Infection with <i>E</i>. <i>histolytica</i> should be considered prior to the administration of corticosteroids, in particular for patients residing in endemic areas or those with appropriate travel history, especially prior to the diagnosis of inflammatory bowel disease. The development of preventative and treatment interventions are needed to improve outcomes of fulminant disease.</p></div

Clinical features and outcomes of cases with severe or fulminant amebic colitis following treatment with corticosteroids, 1991–2016.

<p>Clinical features and outcomes of cases with severe or fulminant amebic colitis following treatment with corticosteroids, 1991–2016.</p

PRISMA flow chart: Data collection and selection of case studies.

<p>PRISMA flow chart: Data collection and selection of case studies.</p

Summary of findings and recommendations.

<p>Summary of findings and recommendations.</p

Invasion of colonic mucosa by amebic trophozoites with resultant inflammatory response.

<p>Colonic biopsy taken from a 49-year-old US male migrant from Mexico, diagnosed with severe amebic colitis after receiving high dose dexamethasone during management of subarachnoid hemorrhage (Courtesy of William A. Petri, Jr., University of Virginia)</p