Isolation and Characterization of an A4 Mycobacteriophage from Central Illinois

Sixteen mycobacteriophages were isolated by students at Illinois Wesleyan University in Bloomington IL using a soil enrichment technique and a Mycobacterium smegmatis host. Each student created and archived a high titer lysate of his or her mycobacteriophage, and of these sixteen, two were selected to be sent in for sequencing, Eidsmoe and Morrow. Morrow was found just outside the Morrow Plots at the University of Illinois at Urbana-Champaign in 2014, and was found to be one of 64 members of the A4 subcluster. Its 51,411 base pair genome is comparable to the average A4 genome of 51,395 base pairs. However, Morrow has 94 genes, which is eight more genes than the average A4 genome. Morrow was then annotated using BLASTp, Phamerator, Starterator, and DNA Master, and was found to be 98% identical to Abdiel, which was found in Missouri in 2011. The identification of the sixteen mycobacteriophages and the sequencing and annotation of two of them expands our knowledge, as well as the online database, where they are contributing to scientific research

Not too close! impact of roommate status on MRSA and VRE colonization and contamination in Nursing Homes

Abstract Multiple room occupancy is common in Nursing Homes (NHs), and its role in transmission of antibiotic-resistant pathogens is unclear. We investigated prevalence of patient colonization and environmental contamination with vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) in NH roommates, compared it with expected prevalence, and determined specific body and environmental sites that may act as sources of roommate colonization. Roommate contamination was associated with index patient’s colonization (relative risk (RR): 2.57 (95% CI 1.04–6.37)) for MRSA, and index patient’s immediate environment contamination for VRE (RR: 3.60 (95% CI 1.59–8.12)). When specific index patient sites associated with roommate colonization were investigated, the side table (Fisher’s p = 0.029 and 0.047 for VRE and MRSA, respectively) and the nurse call button (p = 0.001 and 0.052) stood out, together with patient hands in the case of VRE (p = 0.026). Future studies should be carried out to establish whether these sites should be a specific target of infection prevention campaigns in NHs with multiple occupancy rooms.http://deepblue.lib.umich.edu/bitstream/2027.42/173949/1/13756_2021_Article_972.pd

S-Palmitoylation of γ-Secretase Subunits Nicastrin and APH-1*S⃞

Proteolytic processing of amyloid precursor protein (APP) by β- and γ-secretases generates β-amyloid (Aβ) peptides, which accumulate in the brains of individuals affected by Alzheimer disease. Detergent-resistant membrane microdomains (DRM) rich in cholesterol and sphingolipid, termed lipid rafts, have been implicated in Aβ production. Previously, we and others reported that the four integral subunits of the γ-secretase associate with DRM. In this study we investigated the mechanisms underlying DRM association of γ-secretase subunits. We report that in cultured cells and in brain the γ-secretase subunits nicastrin and APH-1 undergo S-palmitoylation, the post-translational covalent attachment of the long chain fatty acid palmitate common in lipid raft-associated proteins. By mutagenesis we show that nicastrin is S-palmitoylated at Cys689, and APH-1 is S-palmitoylated at Cys182 and Cys245. S-Palmitoylation-defective nicastrin and APH-1 form stable γ-secretase complexes when expressed in knock-out fibroblasts lacking wild type subunits, suggesting that S-palmitoylation is not essential for γ-secretase assembly. Nevertheless, fractionation studies show that S-palmitoylation contributes to DRM association of nicastrin and APH-1. Moreover, pulse-chase analyses reveal that S-palmitoylation is important for nascent polypeptide stability of both proteins. Co-expression of S-palmitoylation-deficient nicastrin and APH-1 in cultured cells neither affects Aβ40, Aβ42, and AICD production, nor intramembrane processing of Notch and N-cadherin. Our findings suggest that S-palmitoylation plays a role in stability and raft localization of nicastrin and APH-1, but does not directly modulate γ-secretase processing of APP and other substrates

Risk of COVID-19 after natural infection or vaccinationResearch in context

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health