Dietary zinc deficiency promotes Acinetobacter baumannii lung infection via IL-13 in mice.

Dietary zinc deficiency is a major risk factor for pneumonia. Acinetobacter baumannii is a leading cause of ventilator-associated pneumonia and a critical public health threat due to increasing rates of multidrug resistance. Patient populations at increased risk for A.

Metal availability shapes early life microbial ecology and community succession.

The gut microbiota plays a critical role in human health and disease. Microbial community assembly and succession early in life are influenced by numerous factors. In turn, assembly of this microbial community is known to influence the host, including immune system development, and has been linked to outcomes later in life.

Fpa (YlaN) is an iron(II) binding protein that functions to relieve Fur-mediated repression of gene expression in .

Iron (Fe) is a trace nutrient required by nearly all organisms. As a result of the demand for Fe and the toxicity of non-chelated cytosolic ionic Fe, regulatory systems have evolved to tightly balance Fe acquisition and usage while limiting overload. In most bacteria, including the mammalian pathogen , the ferric uptake regulator (Fur) is the primary transcriptional regulator controlling the transcription of genes that code for Fe uptake and utilization proteins.

Analysis of genetic requirements and nutrient availability for growth in cystic fibrosis sputum.

is one of the most common pathogens isolated from the lungs of people with cystic fibrosis (CF), but little is known about its ability to colonize this niche. We performed a Tn-seq screen to identify genes necessary for growth in media prepared from CF sputum. We identified 19 genes that were required for growth in all sputum media tested and dozens more that were required for growth in at least one sputum medium.

Restriction of arginine induces antibiotic tolerance in Staphylococcus aureus.

Staphylococcus aureus is responsible for a substantial number of invasive infections globally each year. These infections are problematic because they are frequently recalcitrant to antibiotic treatment. Antibiotic tolerance, the ability of bacteria to persist despite normally lethal doses of antibiotics, contributes to antibiotic treatment failure in S.

MALDI TIMS IMS Reveals Ganglioside Molecular Diversity within Murine Kidney Tissue Abscesses.

Gangliosides play important roles in innate and adaptive immunity. The high degree of structural heterogeneity results in significant variability in ganglioside expression patterns and greatly complicates linking structure and function. Structural characterization at the site of infection is essential in elucidating host ganglioside function in response to invading pathogens, such as ().

FapR regulates HssRS-mediated heme homeostasis in .

, a Gram-positive facultative anaerobe and the causative agent of anthrax, multiplies to extraordinarily high numbers in vertebrate blood, resulting in considerable heme exposure. Heme is an essential nutrient and the preferred iron source for bacteria during vertebrate colonization, but its high redox potential makes it toxic in excess. To regulate heme homeostasis, many Gram-positive bacteria, including , rely on the two-component signaling system HssRS.

An interstrand DNA crosslink glycosylase aids pathogenesis.

Maintenance of DNA integrity is essential to all forms of life. DNA damage generated by reaction with genotoxic chemicals results in deleterious mutations, genome instability, and cell death. Pathogenic bacteria encounter several genotoxic agents during infection.

Coordinated adaptation of to calprotectin-dependent metal sequestration.

Unlabelled: The host protein calprotectin inhibits the growth of a variety of bacterial pathogens through metal sequestration in a process known as "nutritional immunity." growth is inhibited by calprotectin , and calprotectin is localized to staphylococcal abscesses during infection. However, the staphylococcal adaptations that provide defense against nutritional immunity and the role of metal-responsive regulators are not fully characterized.

A multi-species outbreak of VIM-producing carbapenem-resistant bacteria in a burn unit and subsequent investigation of rapid development of cefiderocol resistance.

Carbapenem resistance due to metallo-β-lactamases (MBLs) such as the Verona integron-encoded metallo-β-lactamase (VIM) is particularly problematic due to the limited treatment options. We describe a case series of bacterial infections in a tertiary care hospital due to multi-species acquisition of a VIM gene along with our experience using novel β-lactam antibiotics and antibiotic combinations to treat these infections. Four patients were treated with the combination of ceftazidime-avibactam and aztreonam, with no resistance to the combination detected.

Clostridioides difficile ferrosome organelles combat nutritional immunity.

Iron is indispensable for almost all forms of life but toxic at elevated levels. To survive within their hosts, bacterial pathogens have evolved iron uptake, storage and detoxification strategies to maintain iron homeostasis. Recent studies showed that three Gram-negative environmental anaerobes produce iron-containing ferrosome granules.

Restriction of Arginine Induces Antibiotic Tolerance in .

is responsible for a substantial number of invasive infections globally each year. These infections are problematic because they are frequently recalcitrant to antibiotic treatment, particularly when they are caused by Methicillin-Resistant (MRSA). Antibiotic tolerance, the ability for bacteria to persist despite normally lethal doses of antibiotics, is responsible for most antibiotic treatment failure in MRSA infections.

Iron acquisition by a commensal bacterium modifies host nutritional immunity during Salmonella infection.

During intestinal inflammation, host nutritional immunity starves microbes of essential micronutrients, such as iron. Pathogens scavenge iron using siderophores, including enterobactin; however, this strategy is counteracted by host protein lipocalin-2, which sequesters iron-laden enterobactin. Although this iron competition occurs in the presence of gut bacteria, the roles of commensals in nutritional immunity involving iron remain unexplored.

Maintenance of heme homeostasis in through post-translational regulation of glutamyl-tRNA reductase.

is an important human pathogen responsible for a variety of infections including skin and soft tissue infections, endocarditis, and sepsis. The combination of increasing antibiotic resistance in this pathogen and the lack of an efficacious vaccine underscores the importance of understanding how maintains metabolic homeostasis in a variety of environments, particularly during infection. Within the host, must regulate cellular levels of the cofactor heme to support enzymatic activities without encountering heme toxicity.

Temporal modelling of the biofilm lifecycle (TMBL) establishes kinetic analysis of plate-based bacterial biofilm dynamics.

Bacterial biofilms are critical to pathogenesis and infection. They are associated with rising rates of antimicrobial resistance. Biofilms are correlated with worse clinical outcomes, making them important to infectious diseases research.

Iron acquisition by a commensal bacterium modifies host nutritional immunity during infection.

During intestinal inflammation, host nutritional immunity starves microbes of essential micronutrients such as iron. Pathogens scavenge iron using siderophores, which is counteracted by the host using lipocalin-2, a protein that sequesters iron-laden siderophores, including enterobactin. Although the host and pathogens compete for iron in the presence of gut commensal bacteria, the roles of commensals in nutritional immunity involving iron remain unexplored.

Moving metals: How microbes deliver metal cofactors to metalloproteins.

First row d-block metal ions serve as vital cofactors for numerous essential enzymes and are therefore required nutrients for all forms of life. Despite this requirement, excess free transition metals are toxic. Free metal ions participate in the production of noxious reactive oxygen species and mis-metalate metalloproteins, rendering enzymes catalytically inactive.

Copper ions inhibit pentose phosphate pathway function in Staphylococcus aureus.

To gain a better insight of how Copper (Cu) ions toxify cells, metabolomic analyses were performed in S. aureus strains that lacks the described Cu ion detoxification systems (ΔcopBL ΔcopAZ; cop-). Exposure of the cop- strain to Cu(II) resulted in an increase in the concentrations of metabolites utilized to synthesize phosphoribosyl diphosphate (PRPP).

Application of a quantitative framework to improve the accuracy of a bacterial infection model.

Laboratory models are critical to basic and translational microbiology research. Models serve multiple purposes, from providing tractable systems to study cell biology to allowing the investigation of inaccessible clinical and environmental ecosystems. Although there is a recognized need for improved model systems, there is a gap in rational approaches to accomplish this goal.

MALDI IMS-Derived Molecular Contour Maps: Augmenting Histology Whole-Slide Images.

Imaging mass spectrometry (IMS) provides untargeted, highly multiplexed maps of molecular distributions in tissue. Ion images are routinely presented as heatmaps and can be overlaid onto complementary microscopy images that provide greater context. However, heatmaps use transparency blending to visualize both images, obscuring subtle quantitative differences and distribution gradients.

Elevated transferrin receptor impairs T cell metabolism and function in systemic lupus erythematosus.

T cells in systemic lupus erythematosus (SLE) exhibit multiple metabolic abnormalities. Excess iron can impair mitochondria and may contribute to SLE. To gain insights into this potential role of iron in SLE, we performed a CRISPR screen of iron handling genes on T cells.

How to design an art-science program? Self-reported benefits for artists and scientists in the VI4 artist-in-residence program.

While many new programs bridge the arts and sciences, a data-based examination of art-science program design can lead to more efficient programming. The Vanderbilt Institute for Infection, Immunology, and Inflammation Artist-in-Residence program is a virtual program that brings together undergraduate student "artists" and faculty-level "scientists" to generate science-art content. We have recruited over 80 artists and 50 scientists to collaborate in creating visual science communication content.

Mobilizing an Institutional Research Enterprise to Support Pandemic Diagnostic Care: Establishing a Clinical Laboratory Volunteer Operation.

Context.—: The COVID-19 pandemic has triggered a worldwide crisis that created unprecedented challenges for the health care system, including diagnostic laboratories that faced an ever-increasing demand for SARS-CoV-2 testing.

Objective.

Imaging mass spectrometry reveals complex lipid distributions across biofilm layers.

Introduction: Although is the leading cause of biofilm-related infections, the lipidomic distributions within these biofilms is poorly understood. Here, lipidomic mapping of biofilm cross-sections was performed to investigate heterogeneity between horizontal biofilm layers.

Methods: biofilms were grown statically, embedded in a mixture of carboxymethylcellulose/gelatin, and prepared for downstream matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS).