搜索结果：Microbiological

Cryptococcosis is a severe invasive fungal infection with limited therapeutic options beyond fluconazole-based regimens. Isavuconazole, a broad-spectrum triazole antifungal, has emerged as a potential alternative, although clinical data supporting its use remain scarce. We aimed to evaluate the real-world effectiveness and safety of isavuconazole in patients with different forms of cryptococcosis. A retrospective observational study was conducted at a tertiary-care hospital, including patients with cryptococcosis who received isavuconazole at any treatment phase. Standard microbiological methods were used for pathogen identification and susceptibility testing. Demographic, clinical, and microbiological data were collected. Clinical and microbiological responses and tolerability were assessed at end of treatment or until death. Eight patients with cryptococcosis received isavuconazole, most of whom were immunocompromised. Clinical presentations included pulmonary and disseminated disease, with Cryptococcus neoformans as the predominant species. Isavuconazole was primarily used during the consolidation and maintenance phases, after induction therapy with amphotericin B and flucytosine for 2 weeks in most cases, and as salvage therapy in two patients. It was well tolerated during prolonged treatment (6-12 months). In the two patients with isavuconazole therapeutic drug monitoring, plasma total trough concentrations were within the therapeutic range (5 and 3.5 µg/mL, respectively), whereas cerebrospinal fluid total concentration levels were undetectable. A favorable clinical response was observed in four patients, while three remain on treatment with ongoing clinical improvement; one patient died early. Microbiological clearance was achieved in all culture-positive cases. Isavuconazole demonstrated clinical effectiveness in this cohort of patients across different presentations of cryptococcosis. Treatment was safe and well tolerated, supporting its role as an alternative antifungal option against Cryptococcus, particularly when fluconazole is limited by adverse effects or drug-drug interactions. However, data on central nervous system penetration were limited, and further studies are needed to better define its role in cryptococcal meningitis management.

Bacteremias caused by multidrugresistant bacteria (MDRB) represent a growing public health issue, associated with high morbidity and mortality, prolonged hospitalization, and limited treatment options. The principal objective was to describe the frequency, clinical and microbiological characteristics, and risk factors associated with MDRB bacteremia in adult patients hospitalized in two tertiary-level centers in Córdoba, Argentina. Retrospective, observational and analytical cohort study. Included patients =18 years with true positive blood cultures, from January 2020 to February 2021. Clinical, microbiological features and 30-day mortality were analyzed. Multivariate analysis identified risk factors for MDRB bacteremia. A total of 403 bacteremia episodes were identified, 155 (38.4%) due to MDRB. Thirty-day mortality was higher in MDRO-BSI compared to non-MDRB cases (33.5% vs. 21.8%; p=0.009). Gram-negative bacilli predominated, especially Klebsiella pneumoniae and Escherichia coli. Independent risk factors included: current hospitalization >48 h (aOR: 1.96), ICU admission in the past 6 months (aOR: 1.83), prior antibiotic use within 6 months (aOR: 1.74), and diabetes mellitus (aOR: 1.98). Bacteremias caused by MDRB accounted for a substantial proportion of bloodstream infections and were associated with higher mortality. Identifying risk factors enables the optimization of diagnostic and therapeutic strategies, promoting more efficient and targeted patient care. Introducción: Las bacteriemias por bacterias multirresistentes (BMR) representan un problema creciente en salud pública, asociadas a elevada morbimortalidad, prolongación de la internación y limitación terapéutica. El objetivo principal fue evaluar la frecuencia, características clínicas, microbiológicas y los factores de riesgo asociados a bacteriemias por BMR en pacientes adultos hospitalizados en dos centros de alta complejidad de la ciudad de Córdoba, Argentina. Materiales y métodos: Estudio de cohorte retrospectivo, observacional y analítico. Se incluyeron pacientes =18 años con hemocultivos positivos confirmados, entre enero 2020 y febrero 2022. Se analizaron características clínicas, microbiológicas y evolución a 30 días. Se realizó análisis multivariado para identificar factores asociados a bacteriemias por BMR. Resultados: Se identificaron 403 episodios de bacteriemias, de los cuales 155 (38.4%) fueron causados por BMR. La mortalidad a 30 días fue mayor en bacteriemias por BMR respecto a no-BMR (33.5% vs. 21.8%; p=0.009). Predominaron bacilos Gram negativos, especialmente Klebsiella pneumoniae y Escherichia coli. Los factores de riesgo independientes fueron: hospitalización actual >48 h (ORa: 1.96), ingreso a UCI en 6 meses previos (ORa: 1.83), uso de antibióticos en últimos 6 meses (ORa: 1.74) y diabetes mellitus (ORa: 1.98). Conclusión: Las bacteriemias por BMR representaron una proporción importante entre las bacteriemias y se asocian a mayor mortalidad. La identificación de factores de riesgo permite optimizar las estrategias diagnósticas y terapéuticas, promoviendo una atención más eficiente y dirigida.

Water used in healthcare facilities for human consumption can pose a health risk to patients, healthcare workers, and visitors. Directive (EU) 2020/2184, transposed in Italy by Legislative Decree 18/23 promotes a preventive, risk-based approach along the entire water supply chain through the Water Safety Plans (WSPs). Quantitative Microbial Risk Assessment (QMRA), combined with Cost Benefit Analysis (CBA), allows integrated evaluation of health impacts and economic sustainability of control strategies.This study aimed to develop a decision support method to define a hospital water network surveillance strategy in the Apulia region (Italy) by estimating the risk of Legionella infection and the related costs and benefits under different exposure scenarios. All wards were included, comparing two surveillance strategies: total surveillance (SA) of all water endpoints, and reduced surveillance (SRED), with a limited number of sampling points. Using a Bayesian framework and a dose-response model, the probability of infection and the expected number of Legionnaires' disease cases were estimated for wards with different risk levels. In parallel, CBA evaluated direct costs, including microbiological analyses, point of use filters, and hospitalization days, economic indicators such as Net Benefit (NB), Willingness to Pay (WP), Incremental Cost Effectiveness Ratio (ICER), and Expected Incremental Benefit (EIB). Results showed lower infection probabilities with SA (2.6×10-5-2.95 × 10-7) compared to SRED (3.2×10-5-3.1 × 10-6), with expected cases of 0.4 vs 1.7. However, SRED was more cost-effective (€276,700 vs €422,900), showing positive NB (€149,959) and EIB (€ 348,787) and negative ICER (-9621.7). Even assuming a WTP of €25,000 per prevented case, surveillance costs exceeded benefits.

Urinary tract infections (UTIs) in men, though less frequent than in women, represent a significant clinical challenge due to their increasing incidence with age and distinct microbiological profiles. This expert review analyzed data of urine cultures in men with community-acquired UTIs, collected from emergency departments of 15 french hospitals, from the private laboratory group Atoutbio (21 sites in Meurthe-et-Moselle and the Vosges French departments, alongside primary care records from the AntibioClic tool and the PRIMO database, to characterize the bacterial epidemiology of community-acquired male UTIs in France. Escherichia coli (39-40%) dominated, followed by Enterococcus faecalis (13-15%), Klebsiella pneumoniae (6-8%), and Proteus mirabilis (5-6%). Resistance rates were as follows amoxicillin (47-53.5%), amoxicillin-clavulanate (24-35.7%), trimethoprim-sulfamethoxazole (25.4-31.5%), and fluoroquinolones (16.3-20.2%). Resistance to third-generation cephalosporins (6.6-9.3%) and mecillinam (6.8-8.9%) was lower, while fosfomycin (1.4-1.5%) and nitrofurantoin (0.4-0.7%) retained high susceptibility. Extended-spectrum β-lactamase (ESBL)-producing E. coli ranged from 2 to 8.4%, with carbapenemase producers remaining rare (0.1%). Resistance was higher in men >65 years, particularly in nursing homes, where 3GC resistance reached 15-18%. « Emerging uropathogens » (Aerococcus urinae 1-1.1%, Actinotignum schaalii 0.1-0.4%) were rare. This study highlights the greater microbial diversity in male UTIs compared to women and underscores the need for systematic urine culture, susceptibility testing, and empirical therapy tailored to resistance patterns, age, and risk factors.

Hepatitis B virus (HBV), a major human pathogen, replicates its DNA genome by protein-primed reverse transcription of a pregenomic RNA (pgRNA). This process is directed by the pgRNA-borne epsilon (ε) element, which provides the origin for minus-strand DNA synthesis and mediates coencapsidation of pgRNA with the viral polymerase (P protein) into nucleocapsids. ε adopts a thermodynamically stable hairpin structure that is remodeled upon formation of functional ε-P complexes, but the nature of the rearranged RNA structure and its implication for pgRNA encapsidation has remained elusive. Guided by in silico analyses of ε-like elements from distantly related nackednaviruses, we identify a distinct conformation of HBVε whose defining feature is a cryptic stem-loop (cSL), masked within the upper stem of ε. The P-dependent cSL conformation reorganizes key sequences into a compact structural unit that enables initiation of DNA synthesis and packaging of the viral pgRNA-P complex. RNAs engineered to favor cSL formation exhibit increased P protein affinity and strongly enhanced priming activity in vitro while maintaining replication competence in cells. Mutational analyses identify the cSL and its immediate vicinity, but not the remaining upper stem sequence, as the dominant determinants of ε function. Genetic variation in cSL-forming potential across hepadnaviruses links in vitro priming competence to the energetic accessibility of this alternative fold. Together, our findings reveal ε as a P protein-dependent RNA switch that tightly couples pregenome encapsidation to reverse transcription competence. This regulatory mechanism advances our understanding of HBV replication and could be exploited for antiviral intervention.

To describe the clinical effectiveness and safety of dalbavancin (DAL) for the treatment of Vascular Graft and Endograft Infections (VGEI). A retrospective, single-center observational study was conducted at a tertiary-care university hospital in Rome from January 2020 to December 2024, including all consecutive patients diagnosed with VGEI who received at least one dose of DAL. Cases were identified through the hospital electronic medical record database. VGEIs were diagnosed using MAGIC criteria. Primary outcomes were clinical and radiological response at the end of treatment (EOT) and at six-month follow-up. Thirteen patients were included (median age: 76 years; 92% of males; median Charlson Comorbidity Index 5). Aortic vessels were involved in 61.5% of cases, peripheral vessel in 38.5%. Microbiological identification was achieved in 84.6% of cases, with Staphylococcus aureus (MSSA and MRSA) being the most frequent pathogen. Surgical explant was performed in 53.8% of patients, predominantly for peripheral VGEIs. DAL was used to facilitate early discharge (69.2%) or as suppressive antibiotic therapy (30.8%). No adverse events related to DAL were reported. Clinical success was achieved in 84.6% of patients at EOT and maintained in 61.5% at six-month follow-up. DAL appears to be an effective and well-tolerated option for the management of VGEI, particularly in frail patients or those not eligible for surgery, both to facilitate early discharge and as long-term SAT. Further prospective studies are needed to confirm these findings.

Over the past few decades, the importance of the human gut microbiota has been cast into the limelight. A growing number of studies are attempting to detangle the complex functions of the gut microbiota for human health; however, one existing shortcoming is an incomplete understanding of the microbiota community composition. Up to 70% of bacteria colonizing the human gastrointestinal tract are estimated to lack complete genomic or functional characterization due to their low abundance within the gastrointestinal tract or challenge to culture. As traditional culture methods often favour fast-growing or easily cultured species, alternative strategies are needed to access the broader gut microbial diversity. Here, we propose a novel approach to improve the growth of difficult-to-culture gut bacteria through single-cell microencapsulation, which will allow for in vitro manipulation. This work provides evidence of high biocompatibility of four-arm poly(ethylene glycol) maleimide (PEG4MAL) for gastrointestinal microbial culture and significant anaerobic gut bacteria proliferation in PEG4MAL microbeads generated via microfluidics. Specifically, we varied the concentration of PEG4MAL and the presence of Arg-Gly-Asp peptide motifs to tune the mechanical properties and porosity of the microbeads, and examined their impact on bacterial viability, confluency, and colony formation.

RNA polymerase (RNAP) catalyzes transcription, the first step of gene expression. In bacteria, numerous regulatory proteins and signaling molecules fine-tune RNAP activity in a promoter-specific manner. The resultant changes in gene expression allow cells to acclimate to an ever-changing environment. In addition to phenotypic adaptation, increases in cell fitness can also result from changes in the genome. Here, we explore how mutations in RNAP structural genes benefit cells under diverse selection pressures, with a focus on antibiotics. Selection for resistance to rifampicin (RIF), an antibiotic that binds near the catalytic center of RNAP, leads almost exclusively to amino acid substitutions in the large β subunit that modify the RIF binding site. RIFR mutations have pleiotropic effects and can lead to increased or decreased sensitivity to other antibiotics. In addition, mutations in RNAP are linked to resistance to β-lactams, antibiotics that target peptidoglycan synthesis. Mutations in RNAP can act by altering the interaction with key regulators, including the sigma (σ) factors required for promoter recognition, transcription factors, or signaling molecules that bind to RNAP. RNAP mutations also affect catalysis with impacts on promoter recognition and clearance, elongation, and termination. We consider illustrative examples of changes in RNAP that alter the transcriptional landscape to facilitate the emergence of antibiotic tolerance and resistance, both in the laboratory and during the clinical course of treatment in patients.

Tire and road wear particles introduce complex mixtures of metals and organic additives into soils, yet the primary drivers of their combined toxicity remain poorly resolved. Here, we investigated the individual and combined effects of zinc oxide (ZnO), a major inorganic tire additive, and 6PPD-quinone (6PPD-Q), a toxic transformation product of the tire antioxidant 6PPD, using a soil invertebrate exposure model. A gradient of ZnO concentrations was tested alone and in combination with an environmentally relevant level of 6PPD-Q to simulate co-contaminated soils. While single exposures induced oxidative stress, metabolic perturbation, and gut microbiome alteration, co-exposure under high Zn conditions resulted in increased mortality and growth inhibition relative to single treatments. Chemical analysis revealed enhanced Zn accumulation in organisms under co-exposure, whereas 6PPD-Q bioaccumulation declined at elevated Zn levels, indicating that internal Zn burden was more consistently associated with organism-level impairment than measured internal 6PPD-Q concentration under the tested conditions. Integrated biochemical, histological, and multi-omics analyses showed that co-exposure was associated with enhanced oxidative stress, altered energy metabolism, impaired neuroimmune function, and destabilized gut microbial structure and predicted metabolic potential. Complementary multi-omics analyses revealed coordinated alterations in antioxidant defense, detoxification capacity, and mitochondrial metabolism under high-Zn co-exposure, consistent with a reduced physiological tolerance to chemical stress. Together, these findings support the interpretation that zinc accumulation likely represents a primary contributor to co-exposure toxicity, while 6PPD-quinone may amplify adverse outcomes by constraining organismal stress-buffering capacity. These results highlight the need to consider metal-organic interactions and differential toxic contributions in mixture-based environmental risk assessment of tire-derived contaminants.

Animal gastrointestinal coronaviruses such as porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV) can cause oral infection despite being enveloped viruses, implying that they are capable of passing through the highly acidic gastric lumen. This study focused on the low pH acid resistance of coronaviruses, including PEDV, TGEV and equine coronavirus (ECoV) in fasted-state simulated gastric fluid (FaSSGF) at pH 1.6, which simulated gastric fluid. Interestingly, PEDV, TGEV and ECoV retained infectivity in FaSSGF, whereas SARS-CoV-2 was rapidly inactivated. Although FaSSGF containing surfactants did not affect the acid resistance of these gastrointestinal coronaviruses, FaSSGF including pepsin showed inactivation effects against PEDV, TGEV and ECoV. These findings suggest that animal gastrointestinal coronaviruses possess the potential ability to withstand low pH conditions in gastric acid environments.

The aggressive progression of head and neck cancer (HNC) and the limited availability of effective targeted therapies render it as a significant global health challenge. Several key biological pathways, including PI3K/AKT/mTOR, Wnt/β-catenin, AMPK, and glycolysis, play crucial roles in the progression of HNC. Although conventional therapies such as chemotherapy remain widely utilized, there is a pressing need for innovative interventions to address the major limitations of these approaches. In response to this critical issue, this study seeks to evaluate the efficacy of the FDA-approved drug metformin as an anti-cancer agent. To identify and assess the inhibition of these biological molecules by metformin analogs, we employed a comprehensive in-silico approach that integrated molecular docking, molecular dynamics (MD) simulations, and MM/PBSA (Molecular Mechanics/Generalized Born Surface Area) free energy calculations. PubChem compound CID 222300 emerged as a top-scoring ligand with a high binding affinity for the mTOR protein (PDB: 4JSV). A 100 ns MD simulation was conducted to evaluate the stability and conformational dynamics of the mTOR-ligand complex. The results demonstrated favourable interaction characteristics, including a consistently decreasing radius of gyration (Rg), low root mean square fluctuation (RMSF), and stable root mean square deviation (RMSD), indicating overall structural compaction and stability. Further evidence from hydrogen bond analysis revealed that the ligand contributed to complex stability by maintaining sporadic yet regular polar interactions throughout the trajectory. These findings suggest that CID 222300 is a promising lead compound capable of interacting with the mTOR target in a stable and targeted manner, indicating its potential as a novel therapeutic agent against HNC.

Checkpoint kinase 1 (Chk1) is a vital protein that preserves genomic integrity by regulating cellular responses to DNA damage and replication stress. Because of its key role in cell cycle control, Chk1 has become an attractive target for cancer therapy. Advanced computational methods were used to identify new Chk1 inhibitors, combining REINVENT4 for de novo molecule creation and DeLA-Drug for analogue design. A library of potential molecules was developed from known active compounds using the Mol2Mol generator in REINVENT4. Drug-like properties were verified through ADMET analysis with pkCSM. Three promising candidates, namely, CHD1, CHD2, and CHD3, were selected based on their superior binding free energies (ΔGbind values of -8.92, -6.32, and -5.25 kcal/mol, respectively) compared to the co-crystal ligand 5CV (-4.92 kcal/mol). These candidates were further assessed using molecular dynamics (MD) simulations and MM-GBSA binding free-energy calculations, and the best compound was also subjected to absolute free-energy perturbation (FEP) analysis. The selected compounds were predicted to exhibit high conformational diversity and strong dynamic stability, as demonstrated by free-energy landscape and principal component analyses. The binding disrupted the intramolecular hydrogen-bond network in Chk1 and encouraged the formation of new hydrogen bonds. These results provide a strong foundation for optimizing and developing new Chk1 inhibitors as potential anticancer agents.

This study aims to investigate the causal relationship between gut microbiota and female infertility using a Mendelian randomization (MR) approach. A bidirectional MR analysis was conducted using genome-wide association study (GWAS) data from European populations. Genetic variants (SNPs) linked to 473 bacterial species were used as instrumental variables. Data on female infertility were obtained from the FinnGen study, while gut microbiota-related genetic data were sourced from the NHGRI-EBI GWAS Catalog. Several MR methods, including inverse-variance weighted (IVW) analysis, were employed to assess causal associations. Seven bacterial taxa, including Actinomycetales, Bifidobacterium, Bifidobacteriaceae, Actinobacteria, Prevotella sp002933775, GCA-900199385 sp900320755, and CAG-841 sp002479075, were found to have a protective effect against female infertility. Higher levels of these bacterial taxa were associated with a lower risk of infertility. No evidence of reverse causality was found, indicating a unidirectional relationship between gut microbiota and female infertility. This study supports the concept of a gut-reproductive axis by establishing causal relationships between specific bacterial species and female infertility, suggesting potential avenues for therapeutic interventions.

Klebsiella spp. are pathobionts associated with acute infections, including pneumonia and infections in the urinary tract and bloodstream, often acquired in health-care settings. They represent a global threat owing to the prevalence of multidrug-resistant strains. Moreover, Klebsiella spp., similarly to other members of the human gut microbiota, can contribute to the pathogenesis of non-communicable disorders. In this Review, we describe the taxonomical and molecular characteristics of the Klebsiella genus, as well as its epidemiology and impact as an infectious agent. We also review current evidence that associates Klebsiella spp. with different non-communicable disorders, including chronic inflammatory and metabolic disorders and cancer. We discuss different approaches to target Klebsiella spp., including tailored antibiotics, faecal microbiota transplantation, live biotherapeutic products and bacteriophages. Finally, we discuss the importance of preventative measures, such as epidemiological surveillance, infection control practices and lifestyle interventions, to reduce the spread of Klebsiella spp. in health-care settings and the broader community.

This study compared the developmental and mechanistic toxicity of Tartrazine (TAZ), a synthetic azo dye in food, pharmaceutical, and cosmetic products with its light- (TAZ-LD) and heat-degraded (TAZ-HD) forms as it undergoes photolytic and thermal degradation that may yield reactive by-products with distinct toxicological profiles, using zebrafish model. Embryos exposed to 5-80 mg/L and evaluated for morphology, hatching, larval locomotion, histopathology, oxidative stress and the expression of inflammation and apoptosis-related genes. Compared with the parent dye, both degraded preparations produced greater developmental impairment, including dose-dependent pericardial and yolk-sac edema, axial malformations, delayed or aberrant hatching, and reduced swimming performance; TAZ-HD consistently elicited the strongest effects. Biochemical assays revealed substantially elevated ROS, MDA, and protein carbonyls alongside reduced levels of SOD, CAT, and GSH in degraded-TAZ exposures. Histology showed progressive tissue degeneration and immune infiltration, and gene expression analyses profile indicating pronounced upregulation of pro-inflammatory and pro-apoptotic genes with suppression of bcl2. Collectively, these results demonstrate that physical degradation markedly amplifies the developmental toxicity of TAZ by driving oxidative stress, inflammation, and apoptosis. The findings underscore the need to consider degraded products of TAZ in risk assessments of food colorants and to re-evaluate exposure scenarios reflecting real-world processing and storage conditions.

The AHL (acyl-homoserine lactone)-mediated quorum-sensing (QS) regulatory mechanism is ubiquitously distributed in gram-negative pathogens. In Dickeya oryzae, N-(3-oxo-hexanoyl)-L-homoserine lactone (OHHL), synthesised by ExpIEcz, regulates bacterial swimming motility and virulence. However, the role of its putative cognate receptor ExpREcz has not yet been characterised. In this study, we showed that deletion of expREcz alone did not cause significant changes in various phenotypes associated with D. oryzae physiology and pathogenesis. However, in the absence of a functional OHHL synthase ExpIEcz, ExpREcz was a potent repressor modulating the production of cellulases, polygalacturonases and zeamines, biofilm formation and pathogenicity of D. oryzae EC1, and it was a positive regulator modulating bacterial swimming motility. Further analysis showed that the regulatory activity of ExpREcz was abolished by OHHL, and that the QS signal might relieve the regulation of ExpREcz by interacting with two conserved AHL-binding residues of ExpREcz. Moreover, we found that ExpREcz repressed its own expression through a region in the 5' noncoding region of expREcz that lacks a canonical lux box. These findings suggest that the mechanism may enable D. oryzae to relieve ExpREcz suppression and initiate infection at high cell density when the QS signal reaches a threshold level.

Toxoplasma gondii infection poses a substantial global health burden, yet transmission pathways and population susceptibility in urban informal settlements remain poorly characterised, particularly for women of childbearing age. We analysed archived samples from a cross-sectional serosurvey of 728 children and adolescents aged 4-18 years living in a marginalised urban community in Salvador, Brazil, to characterise exposure patterns and identify demographic, socioeconomic, behavioural, household, and environmental factors associated with seropositivity and to assess spatial heterogeneity in exposure risk. Overall seroprevalence was 49%, increasing with age and higher in males than females; Bayesian serocatalytic models estimated sex-specific forces of infection of 0.078 for males and 0.050 for females, with approximately half of female participants still susceptible upon reaching childbearing age, highlighting the risk of congenital toxoplasmosis. In regression analyses, seropositivity was associated with male sex, lower household income, cat ownership, and residence at lower elevation, greater distance from the main road, and reported contact with sewer water. Notably, most seropositive participants (77.3%) did not live in households with cats. Geostatistical modelling demonstrated fine-scale spatial heterogeneity, with clustered hotspots exceeding 50-60% predicted prevalence. Adjustment for measured covariates attenuated but did not eliminate spatial clustering, indicating residual fine-scale spatial structure consistent with unmeasured environmental processes operating beyond individual households, alongside additional unstructured variation that may reflect household-level or peridomestic differences not captured by the measured covariates. Together, these findings provide evidence consistent with an important role for household and peridomestic environmental exposure pathways in T. gondii transmission in informal settlements, extending beyond households with domestic cats and shaped by social marginalisation and environmental vulnerability.

暂无摘要（点击查看详情）

There is a constant tug-of-war for transition metals at the pathogen-host interface. Vertebrate hosts modulate the availability of metals to pathogens in a process known as nutritional immunity, but pathogens have evolved numerous countermeasures to this host defense strategy. The bioavailability of trace metals therefore shapes the outcome of disease. In mammals, epithelial cells lining the intestine are a major site of metal absorption. Intestinal epithelial cells (IECs) are also a target for invading enteric pathogens but the contribution of epithelium-intrinsic factors toward nutritional immunity is unclear. Using Salmonella enterica serovar Typhimurium (STm) harboring genetically encoded fluorescent sensors for transition metals, we mapped the spatiotemporal nature of metal competition during enteric salmonellosis. In contrast to the metal replete lumen, a subpopulation of STm experience a temporal, cell-specific restriction of Fe2+ and Zn2+ (≤0.1 µM), and possibly Mn2+, in both IECs and cells of the lamina propria during the early stages of infection. We further studied the contribution of the broad specificity divalent metal transporter, SLC11A2, in IECs to nutritional immunity against STm. SLC11A2 was recruited to maturing Salmonella-containing vacuoles and knockout of SLC11A2 led to increased bacterial proliferation in IECs. Metal-responsive fluorescent reporters showed that vacuolar STm were less starved for Fe2+, and possibly Mn2+, but not Zn2+ or Mg2+ in the absence of SLC11A2. STm counters SLC11A2-mediated growth restriction in IECs via the Mn2+/Fe2+ transporter, MntH, and iron-binding siderophores. We conclude that SLC11A2-mediated sequestration of a subset of metals is an IEC innate defense mechanism against STm.