Diclofenac sensitizes multi-drug resistant Acinetobacter baumannii to colistin.

Acinetobacter baumannii causes life-threatening infections that are becoming difficult to treat due to increasing rates of multi-drug resistance (MDR) among clinical isolates. This has led the World Health Organization and the CDC to categorize MDR A. baumannii as a top priority for the research and development of new antibiotics.

Selective regulation of IFN-γ and IL-4 co-producing unconventional T cells by purinergic signaling.

Unconventional T cells, including mucosal-associated invariant T (MAIT), natural killer T (NKT), and gamma-delta T (γδT) cells, comprise distinct T-bet+, IFN-γ+ and RORγt+, IL-17+ subsets which play differential roles in health and disease. NKT1 cells are susceptible to ARTC2-mediated P2X7 receptor (P2RX7) activation, but the effects on other unconventional T-cell types are unknown. Here, we show that MAIT, γδT, and NKT cells express P2RX7 and are sensitive to P2RX7-mediated cell death.

Damsel: analysis and visualisation of DamID sequencing in R.

Summary: DamID sequencing is a technique to map the genome-wide interaction of a protein with DNA. Damsel is the first Bioconductor package to provide an end to end analysis for DamID sequencing data within R. Damsel performs quantification and testing of significant binding sites along with exploratory and visual analysis.

Improved tracking of corneal immune cell dynamics using confocal microscopy.

confocal microscopy (IVCM) is a widely used technique for imaging the cornea of the eye with a confocal scanning light ophthalmoscope. Cellular resolution and high contrast are achieved without invasive procedures, suiting the study of living humans. However, acquiring useful image data can be challenging due to the incessant motion of the eye, such that images are typically limited by noise and a restricted field of view.

Impact of time to antibiotics on clinical outcome in paediatric febrile neutropenia: a target trial emulation of 1685 episodes.

Background: Prompt antibiotic administration for febrile neutropenia (FN) is standard of care, and targets of time to antibiotics (TTA) <60 min are common. We sought to determine the effect of TTA ≥60 versus <60 min on adverse outcomes (intensive care unit (ICU) admission or death) in children with cancer and FN. Effect modification by a decision rule that predicts infection (AUS-rule) and bacteraemia were also investigated.

The Platform Trial In COVID-19 priming and BOOsting (PICOBOO): The immunogenicity, reactogenicity, and safety of licensed COVID-19 vaccinations administered as a second booster in BNT162b2 primed individuals aged 18-<50 and 50-<70 years old.

Objectives: PICOBOO is a randomised, adaptive trial evaluating the immunogenicity, reactogenicity, and safety of COVID-19 booster strategies. Here, we present data for second boosters among individuals aged 18-<50 and 50-<70 years old primed with BNT162b2 until Day (D) 84.

Methods: Immunocompetent adults who had received two doses of BNT162b2 and any licensed COVID-19 booster at least three months prior were eligible.

Staphylococcal superantigens evoke temporary and reversible T cell anergy, but fail to block the development of a bacterium specific cellular immune response.

Superantigens (sAgs) are bacterial virulence factors that induce a state of immune hyperactivation by forming a bridge between certain subsets of T cell receptor (TCR) β chains on T lymphocytes, and class II major histocompatibility complex (MHC-II) molecules; this cross-linking leads to indiscriminate T cell activation, cytokine storm and toxic shock. Here we show that sAg exposure drives the preferential expansion of naive and central memory T cell subsets, but not effector or resident memory T cells, which instead, hyper release pro-inflammatory cytokines. A targeted therapeutic approach to minimise cytokine release by effector memory T cells attenuated sAg-induced cytokine release.

Optimising detection of thrombosis in paediatric Staphylococcus aureus bacteraemia: A prospective interventional sub-study protocol.

Introduction: Staphylococcus aureus bacteraemia (SAB) is the most common cause of sepsis, contributing to paediatric intensive care unit admission in Australia and New Zealand. While deep venous thrombosis (DVT) has been reported in children with invasive S. aureus infections, the actual frequency and possible effects of thrombosis on disease severity and outcome in paediatric SAB remain unknown.

A comprehensive two-hybrid analysis to explore the effector-effector interactome.

Unlabelled: uses over 300 translocated effector proteins to rewire host cells during infection and create a replicative niche for intracellular growth. To date, several studies have identified effectors that indirectly and directly regulate the activity of other effectors, providing an additional layer of regulatory complexity. Among these are "metaeffectors," a special class of effectors that regulate the activity of other effectors once inside the host.

Recovery of culturable Streptococcus pyogenes from swabs stored at different temperatures.

Improving our understanding of superficial Streptococcus pyogenes (Strep A) carriage and transmission necessitates robust sampling methods. Here, we compared the effect of storing swab samples in fridge (+4°C) and freezer (-20°C) conditions on the recovery of laboratory-cultured S. pyogenes.

High incidence of multidrug-resistant tuberculosis in Bhutan: A cohort study based on national TB surveillance data.

Objectives: The emergence of multidrug-resistant tuberculosis (MDR-TB) has made the elimination of TB difficult. Currently, there are limited data on MDR-TB and other drug-resistant TB in Bhutan. We aimed to estimate the incidence and explore the potential risk factors associated with MDR/pre-extensively drug-resistant (pre-XDR)-TB using comprehensive national TB data.

Metabolic profiling unveils enhanced antibacterial synergy of polymyxin B and teixobactin against multi-drug resistant Acinetobacter baumannii.

This untargeted metabolomics study investigated the synergistic antibacterial activity of polymyxin B and Leu-teixobactin, a depsipeptide inhibitor of cell wall biosynthesis. Checkerboard microdilution assays revealed a significant synergy against polymyxin-susceptible and -resistant A. baumannii, excluding lipopolysaccharide-deficient variants.

Inno4Vac Workshop Report Part 1: Controlled Human Influenza Virus Infection Model (CHIVIM) Strain Selection and Immune Assays for CHIVIM Studies, November 2021, MHRA, UK.

Controlled human infection models (CHIMs) are a critical tool for the understanding of infectious disease progression, characterising immune responses to infection and rapid assessment of vaccines or drug treatments. There is increasing interest in using CHIMs for vaccine development and an obvious need for widely available and fit-for-purpose challenge agents. Inno4Vac is a large European consortium working towards accelerating and de-risking the development of new vaccines, including the development of CHIMs for influenza, respiratory syncytial virus and Clostridioides difficile.