Comparative genomics of <i>Staphylococcus capitis</i> reveals species determinants.

Staphylococcus capitis is primarily described as a human skin commensal but is now emergent as an opportunistic pathogen isolated from the bloodstream and prosthetic joint infections, and neonatal intensive care unit (NICU)-associated sepsis. We used comparative genomic analyses of S. capitis to provide new insights into commensal scalp isolates from varying skin states (healthy, dandruff lesional, and non-lesional), and to expand our current knowledge of the species populations (scalp isolates, n = 59; other skin isolates, n = 7; publicly available isolates, n = 120). A highly recombinogenic population structure was revealed, with genomes including the presence of a range of previously described staphylococcal virulence factors, cell wall-associated proteins, and two-component systems. Genomic differences between the two described S. capitis subspecies were explored, which revealed the determinants associated exclusively with each subspecies. The subspecies ureolyticus was distinguished from subspecies capitis based on the differences in antimicrobial resistance genes, β-lactam resistance genes, and β-class phenol soluble modulins and gene clusters linked to biofilm formation and survival on skin. This study will aid further research into the classification of S. capitis and virulence-linked phylogroups to monitor the spread and evolution of S. capitis

An examination of the perceived impact of a continuing interprofessional education experience on opiate prescribing practices

Chronic pain is increasingly recognized as a public health problem. We assessed the effectiveness of a multi-modal, interprofessional educational approach aimed at empowering healthcare professionals to make deliberative changes, especially in opiate prescribing practices. Education activities included enduring webcasts, regional interprofessional roundtable events, and state-level conference presentations within targeted Kentucky and West Virginia regions of the United States. Over 1,000 participants accessed the various activities. For the live events, the largest groups reached included nurses (38.1%), nurse practitioners (31.2%), and physicians (22.1%). In addition to our reach, higher levels of educational effectiveness were measured, specifically, learner’s intentions to change practice patterns, confidence in meeting patient’s needs, and knowledge of pain management guidelines. The majority of the conference (58%) and roundtable (69%) participants stated they intend to make a practice change in one or more areas of chronic pain patient management in post-event evaluation. Differences in pre- and post-activity responses on the measures of confidence and knowledge, with additional comparison to a control population who were not in attendance, were analyzed using non-parametric tests of significance. While neither activity produced significant changes in confidence from pre-activity, participants were more confident post-activity than their control group peers. There were significant changes in knowledge for both live event and webcast participants. Impactful chronic pain continuing the education that emphasizes collaborative care is greatly needed; these results show that the approaches taken here can impact learner’s knowledge and confidence, and hold potential for creating change in how opioid prescribing is managed

Shigella serotypes associated with carriage in humans establish persistent infection in zebrafish

Shigella represents a paraphyletic group of enteroinvasive Escherichia coli. More than 40 Shigella serotypes have been reported. However, most cases within the MSM (men who have sex with men) community are attributed to three serotypes: Shigella sonnei unique serotype and Shigella flexneri 2a and 3a serotypes. Using the zebrafish model, we demonstrate that Shigella can establish persistent infection in vivo. Bacteria are not cleared by the immune system and become antibiotic-tolerant. Persistence depends on O-Antigen, a key constituent of the bacterial surface and serotype determinant. Representative isolates associated with MSM transmission persist in zebrafish, while representative isolates of a serotype not associated with MSM transmission do not. Isolates of a Shigella serotype establishing persistent infections elicited significantly less macrophage death in vivo than isolates of a serotype unable to establish persistence. We conclude that zebrafish are a valuable platform to illuminate factors underlying establishment of Shigella persistent infection in humans

Src Family Kinases and p38 Mitogen-Activated Protein Kinases Regulate Pluripotent Cell Differentiation in Culture

Multiple pluripotent cell populations, which together comprise the pluripotent cell lineage, have been identified. The mechanisms that control the progression between these populations are still poorly understood. The formation of early primitive ectoderm-like (EPL) cells from mouse embryonic stem (mES) cells provides a model to understand how one such transition is regulated. EPL cells form from mES cells in response to l-proline uptake through the transporter Slc38a2. Using inhibitors of cell signaling we have shown that Src family kinases, p38 MAPK, ERK1/2 and GSK3β are required for the transition between mES and EPL cells. ERK1/2, c-Src and GSK3β are likely to be enforcing a receptive, primed state in mES cells, while Src family kinases and p38 MAPK are involved in the establishment of EPL cells. Inhibition of these pathways prevented the acquisition of most, but not all, features of EPL cells, suggesting that other pathways are required. L-proline activation of differentiation is mediated through metabolism and changes to intracellular metabolite levels, specifically reactive oxygen species. The implication of multiple signaling pathways in the process suggests a model in which the context of Src family kinase activation determines the outcomes of pluripotent cell differentiation

The genomic epidemiology of Escherichia albertii

Escherichia albertii is a recently identified gastrointestinal bacterial pathogen of humans and animals which is typically misidentified and generally only detected during genomic surveillance of other Enterobacteriaceae. The incidence of E. albertii is likely underestimated and its epidemiology and clinical relevance are poorly characterised. Here, we whole genome sequenced E. albertii isolates from humans (n = 83) and birds (n = 79) in Great Britain and analysed a broader public dataset (n = 475) to address these gaps. We found human and avian isolates typically (90%; 148/164) belonged to host-associated monophyletic groups with distinct virulence and antimicrobial resistance profiles. Overlaid patient epidemiological data suggested that human infection was likely related to travel and possibly foodborne transmission. The Shiga toxin encoding stx2f gene was associated with clinical disease (OR = 10.27, 95% CI = 2.98–35.45 p = 0.0002) in finches. Our results suggest that improved future surveillance will further elucidate disease ecology and public and animal health risks associated with E. albertii

Comparative efficacy of antimicrobials for treatment of clinical mastitis in lactating dairy cattle: a systematic review and network meta-analysis

A systematic review and network meta-analysis were conducted to assess the relative efficacy of antimicrobial therapy for clinical mastitis in lactating dairy cattle. Controlled trials in lactating dairy cattle with natural disease exposure were eligible if they compared an antimicrobial treatment to a non-treated control, placebo, or a different antimicrobial, for the treatment of clinical mastitis, and assessed clinical or bacteriologic cure. Potential for bias was assessed using a modified Cochrane Risk of Bias 2.0 tool. From 14775 initially identified records, 54 trials were assessed as eligible. Networks were established for bacteriologic cure by bacterial species group, and clinical cure. Disparate networks among bacteriologic cures precluded meta-analysis. Network meta-analysis was conducted for trials assessing clinical cure, but lack of precision of point estimates resulted in wide credibility intervals for all treatments, with no definitive conclusions regarding relative efficacy. Consideration of network geometry can inform future research to increase the utility of current and previous work. Replication of intervention arms and consideration of connection to existing networks would improve the future ability to determine relative efficacy. Challenges in the evaluation of bias in primary research stemmed from a lack of reporting. Consideration of reporting guidelines would also improve the utility of future research

Development of a rat model for glioma-related epilepsy

Seizures are common in patients with high-grade gliomas (30–60%) and approximately 15–30% of glioblastoma (GB) patients develop drug-resistant epilepsy. Reliable animal models are needed to develop adequate treatments for glioma-related epilepsy. Therefore, fifteen rats were inoculated with F98 GB cells (GB group) and four rats with vehicle only (control group) in the right entorhinal cortex. MRI was performed to visualize tumor presence. A subset of seven GB and two control rats were implanted with recording electrodes to determine the occurrence of epileptic seizures with video-EEG recording over multiple days. In a subset of rats, tumor size and expression of tumor markers were investigated with histology or mRNA in situ hybridization. Tumors were visible on MRI six days post-inoculation. Time-dependent changes in tumor morphology and size were visible on MRI. Epileptic seizures were detected in all GB rats monitored with video-EEG. Twenty-one days after inoculation, rats were euthanized based on signs of discomfort and pain. This study describes, for the first time, reproducible tumor growth and spontaneous seizures upon inoculation of F98 cells in the rat entorhinal cortex. The development of this new model of GB-related epilepsy may be valuable to design new therapies against tumor growth and associated epileptic seizures

Lesson of the month: novel method to quantify neutrophil uptake in early lung cancer using SPECT-CT

Neutrophils play an important role in the lung tumour microenvironment. We hypothesised that radiolabelled neutrophils coupled to single-photon emission CT (SPECT) may non-invasively quantify neutrophil uptake in tumours from patients with non-small cell lung cancer. We demonstrated increased uptake of radiolabelled neutrophils from the blood into tumours compared with non-specific uptake using radiolabelled transferrin. Moreover, indium-111-neutrophil activity in the tumour biopsies also correlated with myeloperoxidase (MPO)-positive neutrophils. Our data support the utility of imaging with In-111-labelled neutrophils and SPECT-CT to quantify neutrophil uptake in lung cancer