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Results for “host-microbe interactions”

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PubMed1991

An Agrobacterium two-component regulatory system for the detection of chemicals released from plant wounds.

Crown gall tumorigenesis by Agrobacterium tumefaciens requires the co-ordinate transcriptional induction of a set of pathogenesis genes. At least three classes of environmental stimuli act synergistically to induce these genes: (i) monocyclic aromatic hydrocarbons such as acetosyringone, coniferyl alcohol, and vanillin, (ii) neutral or acidic monosaccharides such as glucose and glucuronic acid, and (iii) acidic pH. Three proteins are required to sense and respond to these stimuli: (i) VirA, a transmembrane sensory protein and histidine protein kinase, (ii) VirG, a transcriptional activator which is phosphorylated by phosphoryl VirA, and (iii) ChvE, a periplasmic sugar-binding protein. VirA and VirG are members of the so-called two-component family of regulatory proteins. This regulatory system continues to offer new discoveries in the areas of signal transduction, host-microbe interactions, and host range.

Gene Expression Regulation, Bacterial↗

PubMed2026

Population heterogeneity in Helicobacter pylori PMSS1 shapes variable mouse infectivity: derivation of the homogeneous reference strain PMSS2.

UNLABELLED: Experimental infection models are widely used to investigate host-microbe interactions, often under the assumption that bacterial populations are genetically uniform. Here, we examined population heterogeneity in the widely used Helicobacter pylori strain PMSS1 and its relationship to variation in mouse infectivity. Single-colony isolates derived from PMSS1 displayed substantial differences in colonization efficiency, indicating that pre-existing variation within the population contributes to infection outcomes. To distinguish the effects of initial population heterogeneity from changes arising during infection, we analyzed PMSS2, a genetically homogeneous reference strain derived from PMSS1 that exhibited consistent infection phenotypes across independently isolated clones. Comparative genomic analysis of isolates recovered from infected mice revealed differences in the extent and patterns of genomic variation between PMSS1- and PMSS2-derived populations. These results demonstrate that variability in infection outcomes can arise from pre-existing heterogeneity within bacterial populations and highlight the importance of considering population composition when interpreting experimental infection studies. IMPORTANCE: Animal infection models are widely used to study how bacterial pathogens cause disease and change during infection. These studies often assume that the bacteria used for infection are genetically uniform. Our study shows that this assumption may not always hold. We found that a commonly used Helicobacter pylori strain contains hidden genetic diversity that leads to large differences in how well bacteria infect mice. By comparing this strain with a genetically uniform derivative, we show how differences present before infection can shape infection outcomes and influence the genetic changes observed during infection. Our findings highlight the importance of considering starting population diversity when interpreting experimental infection studies and are broadly relevant to research on microbial pathogenesis.

Helicobacter pylori↗

PubMed1997

Safe haven: the cell biology of nonfusogenic pathogen vacuoles.

Our understanding of both membrane traffic in mammalian cells and the cell biology of infection with intracellular pathogens has increased dramatically in recent years. In this review, we discuss the cell biology of the host-microbe interaction for four intracellular pathogens: Chlamydia spp., Legionella pneumophila, Mycobacterium spp., and the protozoan parasite Toxoplasma gondii. All of these organisms reside in vacuoles inside cells that have restricted fusion with host organelles of the endocytic cascade. Despite this restricted fusion, the vacuoles surrounding each pathogen display novel interactions with other host cell organelles. In addition to the effect of infection on host membrane traffic, we focus on these novel interactions and relate them where possible to nutrient acquisition by the intracellular organisms.

Animals↗

PubMed2026

Bridging the airway microbiome and targeted therapy in bronchiectasis: multi-omics insights, endotypes and emerging therapies.

Bronchiectasis is a heterogeneous chronic airway disease primarily driven by persistent infection, microbial dysbiosis and dysregulated host immunity. While culture-based microbiology has historically informed clinical management, advances in high-throughput sequencing and multi-omic technologies have transformed our understanding of the airway ecosystem, revealing that disease activity is shaped not only by individual pathogens, but by complex and dynamic host-microbe interactions. Despite the breadth of descriptive microbiome data, translation into clinically actionable diagnostics or therapies has been limited. Importantly, cross-sectional correlations between microbiota and inflammation do not establish cause and effect, underscoring the need to embed host-microbiome profiling within both longitudinal and interventional therapeutic trials. In this review, we critically appraise current microbial and host multi-omics research in bronchiectasis, integrating microbiome studies with host inflammatory, proteomic and immunophenotyping data. We highlight themes emerging across cohorts, including low microbial diversity, pathogen dominance, loss of commensal networks and neutrophil-driven inflammation, and discuss how these features align with biological endotypes associated with exacerbations and treatment response. Drawing on lessons from host-directed therapeutic successes, we examine translational roadblocks limiting microbiome-guided care. We further review emerging microbiome-modulating strategies such as pathogen-specific biologics, bacteriophage therapy, live biotherapeutic products, biofilm-targeting adjuncts and precision antibiotic stewardship. Finally, we propose a roadmap toward microbiome-informed precision medicine through harmonised methodologies, integration of host and microbial biomarkers into clinical trials, and embedding multi-omics pipelines within large international registries. Collectively, these advances have the potential to shift bronchiectasis research and clinical management towards rationally designed, precision medicine-driven therapeutic strategies.

Humans↗

PubMed2026

Insect immune systems: same same but different but still same.

Insects are the most diverse group of animals in nature, occupying nearly every ecological niche and playing central roles as pollinators, pests, and disease vectors. Despite this vast diversity, insects rely on a set of conserved yet evolutionarily adaptable immune pathways to defend against pathogens. Early studies in insect immunity have laid the foundation for human immunology, and recent advances in genomic and transgenic technologies have renewed interest in understanding how immune responses vary across insect orders. Insects are highly diverse in their immune systems; each species has unique immune responses that help fight infections from specific pathogens. Nevertheless, they share multiple aspects of recognition, regulation, and effector mechanisms. This review focuses on current knowledge of the immune systems of major insect lineages to highlight both shared signaling pathways, immune cells, and humoral factors, as well as lineage-specific responses that reflect distinct ecological pressures that have shaped the host-microbe interactions. Comparing different insect species and orders not only provides insights into the evolutionary divergences and convergences of immune system features but also offers complementary knowledge among species within the same order, helping fill existing gaps. Understanding these evolutionary patterns not only deepens our understanding of insect immunity but also informs the development of transgenic strategies to disrupt pathogen transmission in key vector species.

Animals↗

PubMed2026

Autoimmune disease-associated pathobionts: mechanisms and therapeutic potential of phage-based approaches.

The gut microbiota is a critical regulator of systemic immune homeostasis; accumulating evidence implicates specific commensal bacteria, termed "pathobionts," in autoimmune disease pathogenesis. However, the definition of pathobionts remains context-dependent, as their effects are influenced by host genetics and host-microbe interactions. In this review, we summarize representative pathobionts supported by functional evidence in selected extraintestinal autoimmune diseases and discuss how these mechanisms may inform phage-based microbiome-targeted interventions. Mechanistically, pathobionts contribute to autoimmune disease through multiple pathways, including molecular mimicry, induction of intestinal T helper 17 and T follicular helper cell responses, disruption of regulatory T cell homeostasis, intestinal barrier dysfunction, and bacterial translocation from the gut to extraintestinal sites. These processes highlight the central role of gut-associated lymphoid tissue in initiating systemic autoimmunity, and targeting disease-associated microbes represents a promising therapeutic strategy. Whole-phage therapy, which enables highly specific bacterial elimination, has shown efficacy in preclinical immune-mediated disease models, but may be affected by variable in vivo replication, bacterial receptor-mediated resistance, anti-phage immune responses, and ecological effects on the resident microbiome. Phage-derived enzymes that lyse bacterial cell walls, such as endolysins, represent a complementary therapeutic modality that specifically targets bacterial peptidoglycan through cell wall-binding and catalytic domains. Collectively, these findings support the concept that pathobiont-targeted interventions, particularly phage-based strategies, may provide microbiome-directed, immunosuppression-sparing therapeutic approaches for selected patient subsets.

Humans↗

PubMed2026

First Report and Integrated Characterization of Aeromonas veronii Associated with the Protected Fish Diptychus maculatus in Xinjiang, China.

Aeromonas veronii is a widely distributed opportunistic aquatic pathogen associated with diseases in freshwater fish. Despite the ecological and conservation significance of Diptychus maculatus, a protected cold-water fish inhabiting high-altitude ecosystems, information regarding its associated bacterial communities remains limited. This study aimed to isolate and characterize A. veronii recovered from D. maculatus and provide baseline information on its occurrence and phenotypic characteristics. Eight bacterial isolates were recovered from various tissues, including skin, gills, eye, intestine, dorsal fin, body kidney, gonad, and spleen of randomly sampled fish individuals from Xinjiang, China. Phenotypic and biochemical characterization, together with 16S rRNA sequencing, supported their identification as A. veronii, while gyrB analysis of a representative isolate provided additional species-level confirmation. Antimicrobial susceptibility testing revealed a consistent multidrug-resistance phenotype among all isolates. The isolates were susceptible to enrofloxacin, cefotaxime, ceftriaxone, and florfenicol. Intermediate responses were observed for ciprofloxacin, ofloxacin, doxycycline, oxytetracycline, and trimethoprim-sulfamethoxazole, whereas resistance was detected against norfloxacin, neomycin, penicillin, amoxicillin, tetracycline, and erythromycin. In vitro biofilm assays demonstrated weak to moderate biofilm-forming capacity among isolates. These findings provide baseline data for wildlife microbial surveillance and conservation-oriented monitoring of protected fish populations, supporting future investigations into environmental monitoring, genomic characterization, and host-microbe interactions.

Aeromonas veronii↗

PubMed2025

Complete genome sequence and genomic characterization of the probiotic Limosilactobacillus reuteri PSC102.

BACKGROUND: Gut microbiota are potential sources of probiotics and play an essential role in maintaining intestinal health. Limosilactobacillus reuteri PSC102 (L. reuteri PSC102), which was isolated from the feces of healthy pigs, exhibited health-beneficial properties. AIM: We aimed to conduct a whole-genome sequencing analysis of L. reuteri PSC102 to determine its molecular characteristics as a probiotic strain. METHODS: Limosilactobacillus reuteri PSC102 cells were cultured in De Man-Rogosa-Sharpe medium, followed by DNA extraction for genomic analysis using the PacBio-Illumina sequencing platform. The EzBioCloud software was used to perform gene assembly, and the genes were interpreted by the National Center for Biotechnology Information (NCBI) and the Glimmer program. Core and pan-genomic analyses were performed to assess the extent of functional conservation in the genomic sequence. Moreover, the NCBI database and the Basic Local Alignment Search Tool software were used to identify antimicrobial resistance genes and virulence factors. RESULTS: Limosilactobacillus reuteri PSC102 consists of a single circular chromosome with 2,048,626 bp, a guanine- cytosine of 38.9%, 18 rRNA genes, and 69 tRNA genes. Among the 1,846 protein-coding sequences, genes associated with probiotic characteristics were identified, including genes involved in host-microbe interactions, stress tolerance, biogenesis, and defense mechanisms. Furthermore, the genome of L. reuteri PSC102 comprises 2,446 pan-genome and 1,222 core-genome orthologous gene clusters. A total of 74 unique genes were identified in L. reuteri PSC102 genome. These genes mostly encode proteins potentially involved in the transport and metabolism of amino acids and carbohydrates. Moreover, antibacterial resistance genes and virulence factors were absent in L. reuteri PSC102. CONCLUSION: The results of the molecular insight into L. reuteri PSC102 corroborates its use as a probiotic in humans and other animals.

Limosilactobacillus reuteri↗

PubMed1993

Environmental regulation of curli production in Escherichia coli.

Curli are novel surface organelles on E. coli that mediate binding to soluble matrix proteins. The expression of curli is affected by environmental factors, such as temperature, osmolarity, and growth conditions. Curli formation is regulated at the level of transcription, in that the csgA gene can be transcriptionally activated by the cytosolic Crl protein or transcriptionally relieved by a mutation in hns. The expression of curli is also dependent on functional RpoS. E. coli--expressing curli bind to human skin tissue, provided they are precoated with soluble fibronectin, suggesting that curli may act as a colonization factor in host-microbe interactions. Fibronectin is a multifunctional extracellular matrix and plasma protein involved in cell adhesion and cell spreading. It also interacts with a variety of microorganisms, and thus the role of fibronectin in mediating binding of curliated E. coli is of great interest. An investigation of the epitopes of both the fibronectin molecule and the curlin subunit protein involved in the binding of E. coli to tissue will give us more insight into the initial colonization of host surfaces by bacteria.

Amino Acid Sequence↗

PubMed1996

The relation of microbiologic data to aspartate aminotransferase enzyme activity in gingival crevicular fluid.

Gingival crevicular fluid (GCF), reflects the immune and inflammatory reactions and is itself a location for specific host-microbe interactions that lead to periodontal diseases. Aspartate aminotransferase (AST) is one of the components of GCF that is released as a result of cell death. In this study, 40 periodontal sites in 10 early onset periodontitis patients before and after nonsurgical periodontal therapy, with and without local metronidazole administration, were first examined for the AST enzyme levels in GCF and then evaluated for microbiological and clinical variables. In each patient, 4 sites (one site/quadrant) with a probing depth of > or = 5 mm were selected and treated with separate treatment protocols. Certain microbial species including Prevotella intermedia, Porphyromonas gingivalis, and Actinobacillus actinomycetemcomitans(A. a.) were found more often and/or in higher levels in AST active sites (36/40 first measurement--9/36 second measurement), while other species (Streptococcus and Actinomyces) were found more often and/or in higher levels in AST inactive sites (4/40 first measurement--8/36 second measurement). Eight post-treatment AST active sites revealed 1.5 mm of attachment loss, whereas 8 post-treatment AST inactive sites showed 1.37 mm of attachment gain. AST activity and microbiological-clinical data presenting such an agreement suggests that, AST level assessment would be beneficial as an adjunctive method alongside other clinical criteria, in guiding the clinician in periodontal treatment.

Adult↗

PubMed2026

Substrate recognition and cleavage by mucin degrading O-glycopeptidases from the gut microbe Bacteroides caccae.

O-glycopeptidases are enzymes that hydrolyze the peptide bonds in glycoproteins by a mechanism that involves specific recognition of O-linked glycans on the substrate. Bacteroides caccae, an accomplished mucin degrader, is a member of the human gut microbiota with sixteen genes encoding putative O-glycopeptidases in the peptidase_M60 family. At present, the diversity of substrate selectivity in O-glycopeptidases is not well-understood, nor is the rationale behind their expansion in bacteria such as B. caccae. Here, we reveal the activity and diversity of the peptidase_M60 O-glycopeptidases encoded in the B. caccae genome. At least thirteen of the sixteen peptidase_M60 encoding genes produce active mucinolytic enzymes. Targeted functional studies by a high-throughput FRET screen combined with detailed kinetic analyses reveal that five examples in an uncharacterized clade of peptidase_M60 proteins are specifically O-glycopeptidases with different substrate selectivities despite their relatively high degree of relatedness. Structural analyses of these enzymes, including bound complexes, reveal new insight into the molecular underpinnings of O-glycopeptidase diversity. This highlights the larger context of how varied the selectivity of peptidase_M60 O-glycopeptidases can be for the glycan moiety and/or the peptide portion of the substrates, and why mucin degraders like B. caccae diversify O-glycopeptidase substrate repertoires to potentially maximize breakdown of this extraordinarily complex polymer.

Mucins↗

PubMed2026

Symbiotic interactions and climate change implications of the octocoral microbiome.

Octocorals are vital components of tropical, temperate, and cold-water benthic marine ecosystems. Their associated microbiomes, comprising microeukaryotes, prokaryotes, and viruses, are increasingly recognised as central to host health, nutrient cycling, and chemical defence. Metagenomics and amplicon sequencing have uncovered taxonomic and functional complexity within these microbial communities, revealing patterns of host specificity and health status, along with seasonality and geographic structuring. However, anthropogenic stressors, particularly those associated with global climate change, exert intense pressure on coral-dominated ecosystems, leading to complex and poorly understood local and regional patterns of octocoral expansion and mortality. Microbial interactions may be a main driver of these contrasting outcomes by mediating the ecological resilience of octocorals to environmental stress. We synthesise the current state of research on the diversity, organisation, and function of the octocoral microbiome, and identify critical knowledge gaps on octocoral holobionts relative to scleractinian corals. Our meta-analysis of 79 publicly available bacterial genomes from octocorals reveals group-specific specialisation in denitrification and nitrate assimilation, along with widespread capacities for essential amino acid, cofactor, and vitamin production, suggesting important contributions to nutrient cycling in the holobiont. While sampling efforts between cultured and uncultured lineages are even, our genomic survey reveals strong sampling bias toward the Atlantic Ocean, temperate gorgonians, and healthy host states, whereas bacterial genomes representing the pathobiome, tropical and/or deep-sea regions, and other octocoral taxa remain underrepresented. Accordingly, we propose future research directions to advance understanding of octocoral microbiome ecology and its role in the resilience of tropical, temperate and cold-water coral reefs.

Endozoicomonadaceae↗

PubMed1995

[Interaction between anti-infective agents and phagocytes].

Metchnikoff was one of the first to suggest the need for cooperation between phagocytes and therapeutic agents for the benefit of health. After the hopes raised by the discovery and the tremendous development of antimicrobials, there is now a creeping pessimism faced with the parallel evolution of resistance strategies in the microbial world. Interest has now turned to the use of immunomodulatory drugs, alone or combined with anti-infectious agents. Another tendency is based on the possibility that antimicrobials directly interfere with the host-microbe interplay. This review is aimed at summarizing our knowledge of the interactions between antimicrobial agents and the phagocyte, still a cornerstone in the natural defence system. Despite the problems inherent in the analysis and clinical relevance of effects observed in the test tube this developing area of research could provide new therapeutic solutions beyond the year 2000.

Anti-Infective Agents↗

PubMed1996

Assembly of human contact phase proteins and release of bradykinin at the surface of curli-expressing Escherichia coli.

Previous work has demonstrated that most strains of the human pathogen Streptococcus pyogenes bind kininogens through M protein, a fibrous surface protein and virulence determinant. Here we find that strains of several other pathogenic bacterial species, both Gram-positive and Gram-negative, isolated from patients with sepsis, also bind kininogens, especially kininogen (HK). The most pronounced interaction was seen between HK and Escherichia coli. Among clinical isolates of E. coli, the majority of the enterohaemorrhagic, enterotoxigenic, and sepsis strains, but none of the enteroinvasive and enteropathogenic strains, bound HK. Binding of HK to E. coli correlated with the expression of curli, another fibrous bacterial surface protein, and the binding of HK to purified curli was specific, saturable, and of high affinity; Ka = 9 x 10(7) M-1. Other contact phase proteins such as factor XI, factor XII, and prekallikrein bound to curliated E. coli, but not to an isogenic curli-deficient mutant strain, suggesting that contact phase activation may occur at the surface of curliated bacteria. Kininogens are also precursor molecules of the vasoactive kinins. When incubated with human plasma, curli-expressing bacteria absorbed HK. Addition of purified plasma kallikrein to the HK-loaded bacteria resulted in a rapid and efficient release of bradykinin from surface-bound HK. The assembly of contact phase factors at the surface of pathogenic bacteria and the release of the potent proinflammatory and vasoactive peptide bradykinin, should have a major impact on the host-microbe relationship and may contribute to bacterial pathogenicity and virulence.

Bradykinin↗

PubMed2026

Advancing the Deciphering of Host-Microbe Crosstalk with Spatial Omics: A Mini-Review.

Host-microbe crosstalk refers to the reciprocal influences between a host and its resident or invading microorganisms. This crosstalk plays important roles in maintaining host health, regulating physiological functions, and coordinating responses to infection. The rapid rise of spatial omics is transforming how this crosstalk is studied in both animals and plants. Unlike traditional bulk omics, which homogenize tissues and erase spatial context, spatial methods preserve in situ organization and can simultaneously capture molecular information from hosts and microbes. As a result, researchers can characterize the spatial organization of colonization and infection, identify spatial associations between microbial niches and host cell states, and visualize local host response gradients across intact tissues. Current spatial omics technologies encompass sequencing-based, imaging-based, and hybrid platforms. Spatial multi-omics approaches enable the joint measurement or integration of gene expression, protein abundance, and metabolite distributions. Although spatial association alone does not establish causality, spatial omics provides a high-resolution framework for characterizing host-microbe relationships within intact tissues and generating spatially constrained, testable hypotheses. When combined with perturbation experiments and complementary experimental evidence, these hypotheses can contribute to mechanistic interpretation of host-microbe crosstalk. Here, we review spatial omics technologies, compare their suitability and major trade-offs for host-microbe studies, and discuss computational strategies, analytical challenges, and future prospects.

Multiomics↗

PubMed2026

Cross-domain cooperation drives nutrient acquisition and metabolism in the bark beetle holobiont.

Microbial symbiosis underpins host adaptation, yet mechanisms of metabolic integration in holobionts remain unclear. Using metatranscriptomics, genomics, and metabolic assays, we investigated gut microbiome interactions in the European spruce bark beetle (Ips typographus). We observed metabolic complementarity among symbionts and host, forming cross-domain networks that support nutrient acquisition. Nitrogen recycling revealed strong interdependence: no single partner possessed a complete uric acid degradation pathway, but combined evidence supports a distributed pathway spanning beetle, Bacteria, and fungi. Additionally, bacterial nitrate reduction to ammonia indicates a potential nitrogen influx, making otherwise inaccessible inorganic nitrogen available to the host. Shaped by microbial interactions, symbionts also likely supply specific amino acids, while vitamin metabolism showed cross-domain co-metabolism, with Bacteria as main producers of B vitamins, while host and fungi modulated interconversion. Carbohydrate degradation was highly partitioned; bacteria target xylan and pectin, while fungi contribute to glucan breakdown. Crucially, our data provide indirect evidence that the beetle may contribute to complete cellulose degradation, highlighting an underappreciated host role in lignocellulose processing. In terms of enzymatic functional diversity, the bacteriome emerged as the most important microbiome component-an observation that contrasts with the traditional focus on fungi and underscores the need to consider bacterial contributions in insect symbioses. Despite life-stage variation, core metabolic functions remained stable. Overall, metabolic interdependence, rather than microbial composition alone, structures holobiont function. These results highlight functional redundancy and ecological resilience, emphasizing the importance of microbial cooperation and host-microbe metabolic evolution.

Bark beetle↗

PubMed2026

Chemo-selective proteomics in microbial systems.

SUMMARYOver the past two decades, the field of bioorthogonal chemistry has transitioned from emerging to an established cornerstone of scientific inquiry. In parallel, advances in microbial and host-microbe research have highlighted the need for functional approaches that extend beyond genomic and transcriptomic analyses to directly interrogate protein-level activity. Despite this need, proteomic strategies capable of resolving dynamic, heterogeneous, and low-abundance protein populations remain underdeveloped in microbial systems. This review highlights the convergence of chemo-selective proteomic technologies with microbial biology, focusing on bioorthogonal non-canonical amino acid tagging (BONCAT), activity- or affinity-based protein profiling, and bioorthogonal post-translational modifications, and comments on possibilities for novel applications for the use of click chemistry-based tools in the functional interrogation of microbial systems. Together, these strategies enable spatiotemporal resolution of protein synthesis, selective profiling of microbial subpopulations, and direct characterization of protein activity and regulation in complex biological contexts, including single-species cultures, host-associated environments, and polymicrobial communities. Continued development and utilization of these technologies will enable deeper mechanistic insight into how microbial systems function and respond to environmental and host-derived cues.

bioorthogonal chemistry↗

PubMed1989

Host-microbe relationships in chronic respiratory infection.

Infection of the upper and lower respiratory tracts accounts for 85% of the respiratory disease seen by primary-care physicians. Acute infection is usually attributable to microbial virulence but may occur on a background of immune deficiency. Recurrent acute bronchial and pneumonic infection is associated with considerable immunological abnormality (up to 75%) for which a high index of suspicion must be maintained. Chronic bronchial sepsis, on the other hand, has a paradoxically low prevalence of immune deficiency (less than 10%) and the pathogenesis depends on initially compromised mucociliary clearance (by exogenous agents or underlying genetic disease) allowing certain microbes to be selected for airway colonisation according to their ability to release cilio-inhibitory factors and factors damaging ciliated epithelium. Once microbial colonisation is established, the host responds exuberantly with non-specific and immune inflammatory responses which fail to clear the microbial flora but damage the 'innocent bystander' lung. This further compromises bronchial clearance mechanisms in a 'vicious circle' of events whose end result is progressive lung damage and cardio-respiratory failure.

Acute Disease↗