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PubMed2025

Global siRNA screen identifies human host factors critical for SARS-CoV-2 replication and late stages of infection.

Defining the subset of cellular factors governing SARS-CoV-2 replication can provide critical insights into viral pathogenesis and identify targets for host-directed antiviral therapies. While a number of genetic screens have previously reported SARS-CoV-2 host dependency factors, most of these approaches relied on utilizing pooled genome-scale CRISPR libraries, which are biased toward the discovery of host proteins impacting early stages of viral replication. To identify host factors involved throughout the SARS-CoV-2 infectious cycle, we conducted an arrayed genome-scale siRNA screen. Resulting data were integrated with published functional screens and proteomics data to reveal (i) common pathways that were identified in all OMICs datasets-including regulation of Wnt signaling and gap junctions, (ii) pathways uniquely identified in this screen-including NADH oxidation, or (iii) pathways supported by this screen and proteomics data but not published functional screens-including arachionate production and MAPK signaling. The identified proviral host factors were mapped into the SARS-CoV-2 infectious cycle, including 32 proteins that were determined to impact viral replication and 27 impacting late stages of infection, respectively. Additionally, a subset of proteins was tested across other coronaviruses revealing a subset of proviral factors that were conserved across pandemic SARS-CoV-2, epidemic SARS-CoV-1 and MERS-CoV, and the seasonal coronavirus OC43-CoV. Further studies illuminated a role for the heparan sulfate proteoglycan perlecan in SARS-CoV-2 viral entry and found that inhibition of the non-canonical NF-kB pathway through targeting of BIRC2 restricts SARS-CoV-2 replication both in vitro and in vivo. These studies provide critical insight into the landscape of virus-host interactions driving SARS-CoV-2 replication as well as valuable targets for host-directed antivirals.

Humans↗

PubMed2025

Genome-wide identification of modulators of Chlamydia trachomatis parasitophorous vacuole stability highlights an important role for sphingolipid supply.

A mechanistic understanding of how intracellular pathogens evade the intrinsic defenses of their host cells could open up intriguing therapeutic opportunities. Here, we applied a genome-wide genetic screening approach to investigate the nature of the defensive host cell death response suppressed by the membrane trafficking modulator CpoS, an effector protein secreted by the obligate intracellular bacterial pathogen Chlamydia trachomatis. Initially, this work revealed a CpoS-deficient mutant to exhibit a markedly increased dependence on host cellular synthesis of ceramides, the precursors of complex sphingolipids. Using novel microscopic reporters, we then established CpoS' role in defense evasion to occur by preserving the integrity of Chlamydia's parasitophorous vacuole (the inclusion) via ensuring an adequate sphingolipid supply. More specifically, we observed CpoS deficiency to destabilize inclusions, initially characterized by a release of individual bacteria into the host cell cytosol, then followed by inclusion rupture concomitant with host cell death. Exogenous addition of sphingosine stabilized CpoS-deficient inclusions, whereas disruption of host cellular ceramide synthesis destabilized wild-type inclusions. In combination, CpoS deficiency and impaired ceramide synthesis - presumably disrupting both Chlamydia's vesicular and non-vesicular sphingolipid supply routes - destabilized inclusions even earlier, resulting in infection clearance and host cell survival rather than host cell death. Overall, this study highlights how the vacuolar pathogen C. trachomatis maintains vacuole integrity by ensuring a steady sphingolipid supply, potentially offering inspiration and directions for future therapeutic strategies targeting parasitophorous vacuoles.

Chlamydia trachomatis↗

PubMed2026

The value of a prophage-borne defense system in phage-phage competition.

Temperate phages that incorporate into their bacterial hosts' genomes often encode defense systems that protect their hosts from superinfection by unrelated phages. Yet the evolutionary value of such defenses to the phage remains unclear. We present a minimal theoretical framework to quantify the selective advantage of a prophage-borne defense system in competition between temperate phages infecting the same bacterial host. The model reveals regimes in which a "defensive phage" can invade and persist despite growth costs, regimes of bistability, and others in which all phage types coexist due to a rock-paper-scissors-like dynamic between defensive, non-defensive, and defense-loss variants. Because defense systems can be non-transitive, true rock-paper-scissors relations can lead to persistent oscillations. These results identify simple conditions under which phage-encoded defense systems are evolutionarily stable, providing testable predictions for the prevalence and maintenance of these systems in natural microbial communities.

Prophages↗

PubMed2025

Experimental evolution of a pathogen confronted with innate immune memory increases variation in virulence.

Understanding the drivers and mechanisms of virulence evolution is still a major goal of evolutionary biologists and epidemiologists. Theory predicts that the way virulence evolves depends on the balance between the benefits and costs it provides to pathogen fitness. Additionally, host responses to infections, such as resistance or tolerance, play a critical role in shaping virulence evolution. But, while the evolution of pathogens has been traditionally studied under the selection pressure of host adaptive immunity, less is known about their evolution when confronted to simpler and less effective forms of immunity such as immune priming. In this study, we used a well-established insect model for immune priming - red flour beetles and their bacterial pathogen Bacillus thuringiensis tenebrionis - to test how this form of innate immune memory drives the pathogen evolution. Through controlled experimental evolution of the pathogen in primed versus non-primed hosts, we found no change in average virulence after eight selection cycles in primed host. Nonetheless, we observed a notable rise in the variability of virulence, defined as the ability to kill hosts, among independent pathogen lines that evolved in primed hosts, and the bacteria were unable to develop resistance to host priming. Whole genome sequencing revealed increased activity in the bacterial mobilome (prophages and plasmids). Expression of the Cry toxin - a well-known virulence factor - was linked to evolved differences in copy number variation of the cry-carrying plasmid, though this did not correlate directly with virulence. These findings highlight that innate immune memory can drive variability in pathogen traits, which may favor adaptation to variable environments. This underscores the need to consider pathogen evolution in response to innate immune memory when applying these mechanisms in medicine, aquaculture, pest control, and insect mass production.

Animals↗

PubMed2025

Order among chaos: High throughput MYCroplanters can distinguish interacting drivers of host infection in a highly stochastic system.

The likelihood that a host will be susceptible to infection is influenced by the interaction of diverse biotic and abiotic factors. As a result, substantial experimental replication and scalability are required to identify the contributions of and interactions between the host, the environment, and biotic factors such as the microbiome. For example, pathogen infection success is known to vary by host genotype, bacterial strain identity and dose, and pathogen dose. Elucidating the interactions between these factors in vivo has been challenging because testing combinations of these variables quickly becomes experimentally intractable. Here, we describe a novel high throughput plant growth system (MYCroplanters) to test how multiple host, non-pathogenic bacteria, and pathogen variables predict host health. Using an Arabidopsis-Pseudomonas host-microbe model, we found that host genotype and bacterial strain order of arrival predict host susceptibility to infection, but pathogen and non-pathogenic bacterial dose can overwhelm these effects. Host susceptibility to infection is therefore driven by complex interactions between multiple factors that can both mask and compensate for each other. However, regardless of host or inoculation conditions, the ratio of pathogen to non-pathogen emerged as a consistent correlate of disease. Our results demonstrate that high-throughput tools like MYCroplanters can isolate interacting drivers of host susceptibility to disease. Increasing the scale at which we can screen drivers of disease, such as microbiome community structure, will facilitate both disease predictions and treatments for medicine and agricultural applications.

Arabidopsis↗

PubMed2025

Diversification, loss, and virulence gains of the major effector AvrStb6 during continental spread of the wheat pathogen Zymoseptoria tritici.

Interactions between plant pathogens and their hosts are highly dynamic and mainly driven by pathogen effectors and plant receptors. Host-pathogen co-evolution can cause rapid diversification or loss of pathogen genes encoding host-exposed proteins. The molecular mechanisms that underpin such sequence dynamics remains poorly investigated at the scale of entire pathogen species. Here, we focus on AvrStb6, a major effector of the global wheat pathogen Zymoseptoria tritici, evolving in response to the cognate receptor Stb6, a resistance widely deployed in wheat. We comprehensively captured effector gene evolution by analyzing a global thousand-genome panel using reference-free sequence analyses. We found that AvrStb6 has diversified into 59 protein isoforms with a strong association to the pathogen spreading to new continents. Across Europe, we found the strongest differentiation of the effector consistent with high rates of Stb6 deployment. The AvrStb6 locus showed also a remarkable diversification in transposable element content with specific expansion patterns across the globe. We detected AvrStb6 gene losses and evidence for transposable element-mediated disruptions. We used virulence datasets of genome-wide association mapping studies to predict virulence changes across the global panel. Genomic predictions suggested marked increases in virulence on Stb6 cultivars concomitant with the spread of the pathogen to Europe and the subsequent spread to further continents. Finally, we genotyped French bread wheat cultivars for Stb6 and monitored resistant cultivar deployment concomitant with AvrStb6 evolution. Taken together, our data provides a comprehensive view of how a rapidly diversifying effector locus can undergo large-scale sequence changes concomitant with gains in virulence on resistant cultivars. The analyses highlight also the need for large-scale pathogen sequencing panels to assess the durability of resistance genes and improve the sustainability of deployment strategies.

Ascomycota↗

PubMed2025

Influenza A virus RNA localisation and the interceding trafficking pathways of the host cell.

Viruses have evolved to efficiently navigate host cells to deliver, express, and replicate their genetic material. Understanding the mechanisms underlying viral RNA localisation is paramount to designing new antivirals. In this review, we discuss Influenza A Virus (IAV) as a model system to highlight some of the ways in which RNA viruses can hijack the endomembrane systems, as well as nuclear transporters, to achieve the correct localisation of their transcripts. IAV exemplifies a nuclear-replicating RNA virus with a complex and highly regulated RNA localisation and trafficking system within host cells. The virus subverts various vesicular transport systems and nuclear transporters, altering normal cellular functions. IAV RNA trafficking begins during entry; after clathrin-mediated endocytosis, the viral genome (vRNPs) is released into the cytosol after fusion with the endosomal membrane, and it is subsequently imported into the nucleus via the importin system. There, vRNPs engage with most major subnuclear structures and exploit host chromatin, the transcription machinery and splicing apparatus to achieve efficient viral mRNA synthesis and export. Subsequently, newly synthesised vRNPs are rapidly exported from the nucleus and contact the host's recycling endosome network for transport to the plasma membrane. We discuss the critical viral remodelling of the entire endomembrane system, particularly the Rab11 recycling endosome and the endoplasmic reticulum. Lastly, replicated genomes come together into bundles to be inserted in budding virions, and we discuss the current models being proposed and the evidence behind them. Despite advances in understanding these processes, several knowledge gaps remain, particularly regarding the specific export of unspliced IAV transcripts, the remodelling of the endomembrane system, and segment bundling.

Humans↗

PubMed2025

EV-D68 cleaves LARP1 and PABPC1 by 3Cpro to redirect host mRNA translation machinery toward its genomic RNA.

Enterovirus D68 (EV-D68) is an emerging pathogen associated with severe respiratory diseases and neurological complications, such as acute flaccid myelitis. EV-D68 has developed sophisticated mechanisms to hijack host translation machinery, facilitating its replication and impairing host mRNA translation. In this study, we demonstrate that EV-D68 cleaves La-related protein 1 (LARP1) and poly(A)-binding protein cytoplasmic 1 (PABPC1) through its proteases 3Cpro and 2Apro. Our results indicate that overexpressing LARP1 and PABPC1 significantly inhibits EV-D68 replication and reduces the virus-mediated suppression of host translation. While both LARP1 and PABPC1 regulate translation, they exert antiviral effects through distinct mechanisms. We found that LARP1 interacts with the 5'UTR of EV-D68 RNA through its LAM domain, and this interaction is crucial for its antiviral function. LARP1 translation modulation is also influenced by the mTOR and CDK1 signaling pathways. Viral infection inhibits mTOR and CDK1 phosphorylation, which enhances LARP1's binding to viral RNA and inhibits viral translation. To counteract this inhibition, EV-D68 cleaves LARP1 through 3Cpro, thereby promoting efficient viral translation. We also investigated other enteroviruses, such as EV-A71 and CV-A16, which similarly target LARP1 and PABPC1, indicating a conserved mechanism across enteroviruses. Our findings offer new insights into how EV-D68 manipulates host translation and highlight the potential of targeting LARP1 and PABPC1 for antiviral interventions.

Humans↗

PubMed2025

Polysaccharide synthesis operon modulates Rickettsia-endothelial cell interactions.

Pathogenic Rickettsia species target vascular endothelial cells and cause systemic vasculitis. As obligate intracellular bacterial pathogens, Rickettsia must secure nutritional resources within the cytoplasm of endothelial cells while simultaneously subverting the innate immune defense system. With advances in rickettsial and host genetics, recent studies have identified novel molecular mechanisms involved in the complex interactions between Rickettsia and endothelial cells. However, it remains unclear how Rickettsia shields pathogen-derived immune stimulants, such as lipopolysaccharides (LPS) and peptidoglycan fragments, from immune recognition during intracellular replication. Prior work described two Rickettsia conorii variants with kkaebi transposon insertions in the polysaccharide synthesis operon (pso). Biochemical and immunological analyses revealed that pso is responsible for the biosynthesis of O-antigen (O-Ag) and the proper assembly of surface proteins. In the present work, we document that pso variant HK2 exhibits reduced capacities to adhere to and invade microvascular endothelial cells. Despite the low intracellular abundance, HK2 induced significantly higher levels of proinflammatory cytokines and chemokines, leading to premature cell death. Notably, HK2 exhibited defective intracellular survival in bone marrow-derived macrophages. This inability to dampen endothelial cell-mediated immune stimulation and resist macrophage-induced bactericidal activities resulted in the rapid elimination of viable Rickettsia in the mouse model of spotted fever. Further, when tested as a live-attenuated vaccine, HK2 elicited robust protective immunity against lethal spotted fever pathogenesis. Our work highlights the crucial role of pso in enabling Rickettsia to evade immune surveillance during intracellular replication within endothelial cells, ultimately delaying pathogen-induced programmed cell death and escaping immune defense mechanisms.

Operon↗

PubMed2026

Effector loss and gain drives host range at a fitness cost.

Epidemic preparedness depends on tracking microbial evolution that drives shifts in ecological behaviors such as disease emergence. However, the genetic constraints mediating microbial emergence for generalist and specialist behaviors remain poorly described. Here, we addressed this question by combining comparative and functional genomics with phylogeny-based evolutionary analyses of the cereal pathogen Xanthomonas translucens. We show that a generalist X. translucens subgroup arose from a specialist ancestor, and the loss of a single effector gene, xopAL1, contributed to the generalist host expansion by promoting host jump from barley to wheat. Deleting barley-specialist X. translucens xopAL1 recapitulated the host jump to wheat and demonstrates risk across each globally distributed genetic lineage. However, this niche expansion via XopAL1 loss incurs a significant fitness cost to colonize barley. Moreover, the specialist lineage gained an additional effector gene, xopAJ, which enhanced virulence on barley while restricting oat infection, thereby reinforcing niche specialization. We further conducted transcriptomic analysis of wheat and determined that XopAL1 triggers a defense response that involves the reduction of photosynthetic processes. Our work provides an experimentally validated evolutionary framework to understand mechanisms of intergenera host jump. Overall, we demonstrate that single events of gene loss and gain shape ecological behaviors by creating a dynamic trade-off between niche breadth and specialization.

Triticum↗

PubMed2026

The hidden costs of using media to mimic the hosts of Fusarium graminearum: An epigenetic perspectives.

Pathogens dynamically reprogrammed gene expression when transitioning between nonhost and host environments. Epigenetic regulation can provide a rapid and reversible mechanism for this shift. Using published data from Shao et al. (2024) and Zhao et al. (2024), we compare chromatin states in the fungus Fusarium graminearum under in vitro trichothecene mycotoxin (deoxynivalenol) inducing conditions and during wheat spike infection. This revealed striking differences in H3K4me3 and H3K27me3 landscapes with the two datasets showing limited overlap in marked genes and distinct genomic distributions. This indicates that chemically induced cultures only partially replicate the complex signals encountered in planta and emphasise the need for infection-reflective experimental designs to accurately characterise pathogenicity mechanisms.

Fusarium↗

PubMed2026

Rasputin/G3BP mediates subversion of antiviral immunity by o'nyong-nyong virus in Anopheles coluzzii.

Cellular G3BP proteins are essential for alphavirus infection in both vertebrate and mosquito hosts, but the underlying mechanism of their proviral activity is poorly understood in any host. Whether the mosquito G3BP ortholog, Rasputin (Rin), interacts with host immunity to influence alphavirus infection has not been investigated, and anopheline mosquito interactions with arboviruses have been little studied. Here, we find that Rin silencing in Anopheles mosquitoes results in decreased ONNV infection levels, indicating a proviral activity for Anopheles Rin. We find that Rin function is required to maintain basal activity of the antiviral Imd and JAK/STAT pathways in uninfected mosquitoes. However, during ONNV infection, the control of the Imd pathway by Rin activity appears corrupted because Rin silencing leads to overexpression of the Imd positive regulator, Rel2. Thus, silencing of Rin both augments Rel2 transcript abundance and decreases ONNV load. Co-silencing of Rel2 with Rin restores normal ONNV infection levels, indicating that Rin activity is required to inhibit Imd function during ONNV infection, and which explains most of the Rin proviral phenotype. In addition, we show that the ONNV non-structural protein 3 (nsP3), which binds to Rin, strongly alters the pattern of Anopheles cellular protein partners interacting with Rin. In the presence of ONNV nsP3, 48 Rin-binding host proteins are unchanged but seven binding proteins are excluded and eight new cellular proteins bind Rin. The altered cellular protein partners are candidate host factors involved in viral subversion of Rin control over Imd activity. Overall, these results reveal a molecular mechanism in which ONNV, probably through nsP3, co-opts the normal Rin function for basal cellular immune activity by subverting the Imd antiviral pathway to promote infection. These results may be generalizable for Rin function during alphavirus infection of other mosquitoes, as well as for G3BP function in the mammalian host, and could offer a target for development of vector-based genetic control tools against arbovirus transmission.

Animals↗

PubMed2026

Parallel single-cell host immune profiling and pathogen genomic characterization in Klebsiella-associated sepsis: a pilot study.

OBJECTIVES: Sepsis is a life-threatening syndrome characterized by profound immune dysregulation and substantial biological heterogeneity. Here, we conducted a pilot study to explore host immune remodeling in Klebsiella-associated sepsis by combining single-cell RNA sequencing of peripheral blood mononuclear cells with whole-genome sequencing of the corresponding bloodstream isolates. METHODS: In this prospective observational pilot study, we analyzed peripheral blood mononuclear cells (PBMCs) from two patients with Klebsiella-associated sepsis and two healthy controls (HC) using single-cell RNA sequencing. PBMC composition, differential transcriptional responses, and pathway analysis were assessed across immune subsets. The corresponding bloodstream isolates were characterized by phenotypic antimicrobial susceptibility testing and whole-genome sequencing. RESULTS: Compared to HC, septic patients showed expansion of the myeloid compartment and contraction of the NK/T compartment. High-resolution analysis suggested shifts within lymphoid populations. At the transcriptional level, sepsis was associated with compartment-specific enrichment of interferon-related and host-defence pathways, as well as oxidative phosphorylation, ATP synthesis, and mitochondrial electron transport signatures across multiple PBMC subsets. Classical monocytes exhibited a coordinated decrease in MHC class II-related transcripts. The sepsis-associated isolates were identified as Klebsiella pneumoniae and Klebsiella variicola and were notable for overall antimicrobial susceptibility, limited resistomes, and absence of canonical hypervirulence determinants. CONCLUSION: Our data provide a preliminary description of immune remodeling during Klebsiella-associated sepsis and suggest that severe clinical disease may be associated with isolates lacking classical multidrug-resistance or hypervirulence features. These findings should be interpreted as preliminary and hypothesis-generating and require validation in larger cohorts with detailed clinical severity assessment.

Female↗

PubMed2024

Role of the Pseudomonas plecoglossicida fliL gene in immune response of infected hybrid groupers (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂).

Pseudomonas plecoglossicida, a gram-negative bacterium, is the main pathogen of visceral white-point disease in marine fish, responsible for substantial economic losses in the aquaculture industry. The FliL protein, involved in torque production of the bacterial flagella motor, is essential for the pathogenicity of a variety of bacteria. In the current study, the fliL gene deletion strain (ΔfliL), fliL gene complement strain (C-ΔfliL), and wild-type strain (NZBD9) were compared to explore the influence of the fliL gene on P. plecoglossicida pathogenicity and its role in host immune response. Results showed that fliL gene deletion increased the survival rate (50%) and reduced white spot disease progression in the hybrid groupers. Moreover, compared to the NZBD9 strain, the ΔfliL strain was consistently associated with lower bacterial loads in the grouper spleen, head kidney, liver, and intestine, coupled with reduced tissue damage. Transcriptomic analysis identified 2 238 differentially expressed genes (DEGs) in the spleens of fish infected with the ΔfliL strain compared to the NZBD9 strain. Based on Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, the DEGs were significantly enriched in seven immune system-associated pathways and three signaling molecule and interaction pathways. Upon infection with the ΔfliL strain, the toll-like receptor (TLR) signaling pathway was activated in the hybrid groupers, leading to the activation of transcription factors (NF-κB and AP1) and cytokines. The expression levels of proinflammatory cytokine-related genes IL-1β, IL-12B, and IL-6 and chemokine-related genes CXCL9, CXCL10, and CCL4 were significantly up-regulated. In conclusion, the fliL gene markedly influenced the pathogenicity of P. plecoglossicida infection in the hybrid groupers. Notably, deletion of fliL gene in P. plecoglossicida induced a robust immune response in the groupers, promoting defense against and elimination of pathogens via an inflammatory response involving multiple cytokines.

Animals↗

PubMed2026

Genome-wide transcriptional landscape of Mycobacterium tuberculosis during acute lung infection.

Tuberculosis (TB) remains a major global health burden, yet the mechanisms by which Mycobacterium tuberculosis (Mtb) adapts to host environments to drive disease pathology are incompletely defined. A key limitation has been reliance on axenic culture systems that fail to recapitulate the complex, host-imposed stresses encountered by Mtb in vivo. Here, we report the first microarray-based genome-wide transcriptomic profiling of Mtb in rabbit lungs with active TB, which closely mirrors human disease features, including granuloma heterogeneity, necrosis, and cavitation. Using Mtb RNA isolated from infected lung homogenates or broth-culture, we capture bacterial transcriptional states shaped by the host microenvironments. The transcriptional data analyses reveal extensive, context-dependent reprogramming of Mtb metabolic, respiratory, and stress-response networks that diverges markedly from in vitro expression profiles, including activation of stress adaptation, lipid catabolism, nucleic acid metabolism, and transcriptional regulation pathways. These data uncover pathways and networks that are selectively engaged in vivo and likely critical for Mtb survival within granulomatous lesions. Our findings demonstrate that transcriptional states most relevant to TB pathogenesis are underrepresented in standard lab-grown Mtb models and highlight the importance of in vivo bacterial profiling. By characterizing Mtb gene expression within diseased lungs, this study provides a systems-level framework for understanding TB pathogenesis and reveals in vivo-essential pathways, offering potential targets for translational drug discovery and the development of more effective anti-TB therapies.

Animals↗

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↗

PubMed2025

Stepping out of the dark: how metabolomics shed light on fungal biology.

Metabolomics, a critical tool for analyzing small-molecule metabolites, integrates with genomics, transcriptomics, and proteomics to provide a systems-level understanding of fungal biology. By mapping metabolic networks, it elucidates regulatory mechanisms driving physiological and ecological adaptations. In fungal pathogenesis, metabolomics reveals host-pathogen dynamics, identifying virulence factors like gliotoxin in Aspergillus fumigatus and metabolic shifts, such as glyoxylate cycle upregulation in Candida albicans. Ecologically, it highlights fungal responses to abiotic stressors, including osmolyte production like trehalose, enhancing survival in extreme environments. These insights highlight metabolomics' role in decoding fungal persistence and niche colonization. In drug discovery, it aids target identification by profiling biosynthetic pathways, supporting novel antifungal and nanostructured therapy development. Combined with multi-omics, metabolomics advances insights into fungal pathogenesis, ecological interactions, and therapeutic innovation, offering translational potential for addressing antifungal resistance and improving treatment outcomes for fungal infections. Its progress shed light on complex fungal molecular profiles, advancing discovery and innovation in fungal biology.

Metabolomics↗

PubMed1992

Epizootics of Salmonella infection in poultry may be the result of modern selective breeding practices.

This paper discusses the hypothesis that a major factor in the epizootics of Salmonella infection in poultry is a declining host genetic diversity. A computer model is described which is based on models that have been previously used to investigate host-pathogen coevolution in cereal crops. It is shown that, as host genetic diversity declines, parasite diversity also declines to a lower equilibrium level. With a highly diverse host, parasite numbers decline to zero. With a homogeneous host population, after an initial decline, there is a rapid increase in parasite numbers, due to the selection of a particularly well adapted parasite strain. This simple computer simulation is used as the basis for a discussion of the literature supporting the suggestion that a major factor in the epizootic of Salmonella in poultry is related to the low genetic diversity of commercial poultry flocks.

Animals↗