Tackling microbial iron homeostasis: novel antimicrobial strategies.

The escalating threat of antimicrobial resistance demands innovative therapeutic strategies beyond classical targets. Recent insights into the mechanisms of bacterial iron acquisition - ranging from siderophores and heme uptake to ferrous iron transport - have enabled new approaches to impair pathogen growth and virulence. These pathways are increasingly being harnessed for therapeutic gain.

Association between coronary monosodium urate deposits at DECT and high-risk coronary plaque phenotypes and other features in gout patients.

Background: Dual-energy computed tomography (DECT) detects monosodium urate (MSU) deposits in joints. However, the correlation between coronary atherosclerosis phenotypes and MSU-positive lesions in the cardiovascular system remains unclear. We investigated the correlation between coronary MSU-positive plaques on unenhanced DECT with the coronary atherosclerosis profile at coronary CT angiography.

The common genetic variant rs1278960 determining expression of Interferon-lambda predicts inflammatory response in critically ill COVID-19 patients.

The single nucleotide polymorphism rs12979860 is associated with the production of IFNλ4, a type III interferon, which offers protection from viral infection via its proinflammatory properties. We investigated if a genetically determined increase in IFNλ4 affects disease progression in SARS-CoV-2. This prospective, single-center study involved critically ill SARS-CoV-2 patients admitted to the intensive care unit.

Prevalence of iron deficiency in acute and chronic heart failure according to different clinical definitions.

Aims: Iron is essential to maintain cellular energy metabolism in the myocardium. Impaired cellular iron availability negatively affects myocardial physiology and can aggravate heart failure (HF). Iron deficiency (ID) is frequently found in patients with acute and chronic HF (AHF, CHF) and associated with clinical outcome.

Severe COVID-19 disease is associated with genetic factors affecting plasma ACE2 receptor and CRP concentrations.

A hyperinflammatory state with highly elevated concentrations of inflammatory biomarkers such as C-reactive protein (CRP) is a characteristic feature of severe coronavirus disease 2019 (COVID-19). To examine a potential role of common genetic factors that may influence COVID-19 outcomes, we investigated whether individuals with a polygenic predisposition for a pro-inflammatory response (in the form of Polygenic Scores) are more likely to develop severe COVID-19. The innovative approach of polygenic scores to investigate genetic factors in COVID-19 severity should provide a comprehensive approach beyond single-gene studies.

The influence of serum uric acid on coronary atherosclerosis plaque phenotypes by computed tomography angiography: The missing link?

Background And Aims: The interaction of serum uric acid (SUA) with atherogenesis is incompletely understood. Aim of our study was to investigate the association of SUA levels with coronary plaque composition including high-risk-plaque (HRP) features by coronary computed tomography angiography (CTA) and for the prediction of major adverse cardiac events (MACE).

Methods And Results: 1242 patients (age 66.

Tissue Iron Distribution in Anemic Patients with End-Stage Kidney Disease: Results of a Pilot Study.

: Anemia is a frequent multifactorial co-morbidity in end-stage kidney disease (ESKD) associated with morbidity and poor QoL. Apart from insufficient erythropoietin formation, iron deficiency (ID) contributes to anemia development. Identifying patients in need of iron supplementation with current ID definitions is difficult since no good biomarker is available to detect actual iron needs.

Review: The Role of Dual-Energy Computed Tomography in Detecting Monosodium Urate Deposits in Vascular Tissues.

Purpose Of Review: To highlight novel findings in the detection of monosodium urate deposits in vessels using dual energy computed tomography, and to discuss the potential clinical implications for gout and hyperuricemia patients.

Recent Findings: Gout is an independent risk factor for cardiovascular disease. However, classical risk calculators do not take into account these hazards, and parameters to identify patients at risk are lacking.

Major cardiovascular events in patients with cardiovascular monosodium urate deposits in atherosclerotic plaques.

Objective: To determine the association of cardiovascular atherosclerotic plaque monosodium urate deposits with the occurrence of major cardiovascular events in gout and hyperuricemia patients.

Methods: This retrospective cohort study included patients with clinically suspicion of gout, who performed a dual energy computed tomography of the affected limb and thorax between 1 June 2012 and 5 December 2019. Clinical and laboratory parameters were retrieved from patients' charts.

Detailed stratified GWAS analysis for severe COVID-19 in four European populations.

Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended genome-wide association meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.

DMT1 Protects Macrophages from Infection by Controlling Cellular Iron Turnover and Lipocalin 2 Expression.

Macrophages are at the center of innate pathogen control and iron recycling. Divalent metal transporter 1 (DMT1) is essential for the uptake of non-transferrin-bound iron (NTBI) into macrophages and for the transfer of transferrin-bound iron from the endosome to the cytoplasm. As the control of cellular iron trafficking is central for the control of infection with siderophilic pathogens such as Typhimurium, a Gram-negative bacterium residing within the phagosome of macrophages, we examined the potential role of DMT1 for infection control.

Alterations of blood monocyte subset distribution and surface phenotype are linked to infection severity in COVID-19 inpatients.

Severe coronavirus disease 19 (COVID-19) manifests with systemic immediate proinflammatory innate immune activation and altered iron turnover. Iron homeostasis, differentiation, and function of myeloid leukocytes are interconnected. Therefore, we characterized the cellularity, surface marker expression, and iron transporter phenotype of neutrophils and monocyte subsets in COVID-19 patients within 72 h from hospital admission, and analyzed how these parameters relate to infection severity.

Quantity of IgG response to SARS-CoV-2 spike glycoprotein predicts pulmonary recovery from COVID-19.

The CovILD study is a prospective, multicenter, observational cohort study to systematically follow up patients after coronavirus disease-2019 (COVID-19). We extensively evaluated 145 COVID-19 patients at 3 follow-up visits scheduled for 60, 100, and 180 days after initial confirmed diagnosis based on typical symptoms and a positive reverse transcription-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We employed comprehensive pulmonary function and laboratory tests, including serum concentrations of IgG against the viral spike (S) glycoprotein, and compared the results to clinical data and chest computed tomography (CT).

Nifedipine Potentiates Susceptibility of Typhimurium to Different Classes of Antibiotics.

The calcium channel blocker nifedipine induces cellular iron export, thereby limiting the availability of the essential nutrient iron for intracellular pathogens, resulting in bacteriostatic activity. To study if nifedipine may exert a synergistic anti-microbial activity when combined with antibiotics, we used the mouse macrophage cell line RAW267.4, infected with the intracellular bacterium Typhimurium, and exposed the cells to varying concentrations of nifedipine and/or ampicillin, azithromycin and ceftriaxone.

Baseline iron status and presence of anaemia determine the course of systemic Salmonella infection following oral iron supplementation in mice.

Background: Iron deficiency anaemia (IDA) is a major health concern. However, preventive iron supplementation in regions with high burden of infectious diseases resulted in an increase of infection related morbidity and mortality.

Methods: We fed male C57BL/6N mice with either an iron deficient or an iron adequate diet.

Pharmacological Targeting of BMP6-SMAD Mediated Hepcidin Expression Does Not Improve the Outcome of Systemic Infections With Intra-Or Extracellular Gram-Negative Bacteria in Mice.

Introduction: Hepcidin is the systemic master regulator of iron metabolism as it degrades the cellular iron exporter ferroportin. In bacterial infections, hepcidin is upregulated to limit circulating iron for pathogens, thereby increasing iron retention in macrophages. This mechanism withholds iron from extracellular bacteria but could be of disadvantage in infections with intracellular bacteria.

Ferritin H deficiency deteriorates cellular iron handling and worsens Salmonella typhimurium infection by triggering hyperinflammation.

Iron is an essential nutrient for mammals as well as for pathogens. Inflammation-driven changes in systemic and cellular iron homeostasis are central for host-mediated antimicrobial strategies. Here, we studied the role of the iron storage protein ferritin H (FTH) for the control of infections with the intracellular pathogen Salmonella enterica serovar Typhimurium by macrophages.

Overcoming limitations in the availability of swabs systems used for SARS-CoV-2 laboratory diagnostics.

The diagnosis of COVID-19 relies on the direct detection of SARS-CoV-2 RNA in respiratory specimens by RT-PCR. The pandemic spread of the disease caused an imbalance between demand and supply of materials and reagents needed for diagnostic purposes including swab sets. In a comparative effectiveness study, we conducted serial follow-up swabs in hospitalized laboratory-confirmed COVID-19 patients.

Iron in immune cell function and host defense.

The control over iron availability is crucial under homeostatic conditions and even more in the case of an infection. This results from diverse properties of iron: first, iron is an important trace element for the host as well as for the pathogen for various cellular and metabolic processes, second, free iron catalyzes Fenton reaction and is therefore producing reactive oxygen species as a part of the host defense machinery, third, iron exhibits important effects on immune cell function and differentiation and fourth almost every immune activation in turn impacts on iron metabolism and spatio-temporal iron distribution. The central importance of iron in the host and microbe interplay and thus for the course of infections led to diverse strategies to restrict iron for invading pathogens.

Cardiopulmonary recovery after COVID-19: an observational prospective multicentre trial.

Background: After the 2002/2003 severe acute respiratory syndrome outbreak, 30% of survivors exhibited persisting structural pulmonary abnormalities. The long-term pulmonary sequelae of coronavirus disease 2019 (COVID-19) are yet unknown, and comprehensive clinical follow-up data are lacking.

Methods: In this prospective, multicentre, observational study, we systematically evaluated the cardiopulmonary damage in subjects recovering from COVID-19 at 60 and 100 days after confirmed diagnosis.

Persisting alterations of iron homeostasis in COVID-19 are associated with non-resolving lung pathologies and poor patients' performance: a prospective observational cohort study.

Background: Severe coronavirus disease 2019 (COVID-19) is frequently associated with hyperinflammation and hyperferritinemia. The latter is related to increased mortality in COVID-19. Still, it is not clear if iron dysmetabolism is mechanistically linked to COVID-19 pathobiology.

Cell-specific expression of determines the outcome of serovar Typhimurium infection in mice.

Mutations in HFE cause hereditary hemochromatosis type I hallmarked by increased iron absorption, iron accumulation in hepatocytes and iron deficiency in myeloid cells. HFE encodes an MHC-I like molecule, but its function in immune responses to infection remains incompletely understood. Here, we investigated putative roles of Hfe in myeloid cells and hepatocytes, separately, upon infection with Salmonella Typhimurium, an intracellular bacterium with iron-dependent virulence.