Nat Commun. 2026 Jan 14. doi: 10.1038/s41467-026-68495-0. Online ahead of print.

ABSTRACT

Fecal coprolites preserve ancient microbiomes and are a potential source of extinct but highly efficacious antimicrobial peptides (AMPs). Here, we develop AMPLiT (AMP Lightweight Identification Tool), an efficient tool deployable to portable hardware for AMP screening in metagenomic datasets. AMPLiT demonstrates AUPRC performances of 0.9486 ± 0.0003 and reasonable overall training time of 3200 ± 53 s. By computationally utilizing AMPLiT, we analyze seven ancient human coprolite metagenomes, identifying 160 AMP candidates. Of 40 representative peptides synthesized, 36 (90%) peptides demonstrate measurable antimicrobial activity at 100 μM or less in vitro. Strikingly, approximately two-thirds of these peptides are sourced from Segatella copri, a dominant ancient gut commensal that is conspicuously underrepresented in modern populations, particularly those with Westernized lifestyles. Representative S. copri-derived AMPs exhibit disruptions against membranes of pathogenic bacteria, coupled with low cytotoxicity and hemolytic risk. In vivo, lead peptides demonstrate potent antibacterial and wound-healing efficacy comparable to traditional antibiotics, especially in combating gram-positive pathogens. Our findings highlight the ancient gut microbiomes as sources of novel AMPs, offering valuable insights into the historical role of S. copri in human health and its decline in contemporary populations.

PMID:41535683 | DOI:10.1038/s41467-026-68495-0

Int J Biol Macromol. 2026 Jan;340(Pt 2):150111. doi: 10.1016/j.ijbiomac.2026.150111. Epub 2026 Jan 8.

ABSTRACT

Salmonella Typhimurium poses critical safety risks owing to its multidrug resistance and persistence in food matrices. To address this threat, we focused on microcin Y (MccY) a lasso peptide with potent activity against multidrug-resistant S. typhimurium and elucidated how mutations in the FhuA/SbmA receptors mediate MccY resistance and differentially affect bacterial virulence. Molecular docking revealed that MccY tended to bind to the N-terminal segment of FhuA within its β-barrel cavity, with key interaction sites including FhuA_564Leu-MccY_5His (2.5 Å hydrogen bond, MIC = 200 μg/mL) and sites such as FhuA_129Ser/FhuA_147Asn (MIC = 100-200 μg/mL). For SbmA, MccY forms hydrogen bonds with SbmA_204Asn-MccY_20Tyr (3.1 Å, MIC = 1.0 μg/mL), SbmA_320Asn-MccY_21Gly (2.9 Å, MIC = 200 μg/mL), and SbmA_361Gln-MccY_21Gly (2.9 Å, MIC = 2.0 μg/mL). The susceptibility of MccY's lasso structure domains to resistance was ranked as follows: tail < ring < loop. FhuA/SbmA mutations enhance MccY resistance (MIC>250 μg/mL) via receptor conformational changes, with FhuA_Ala63Gly, and FhuA_401Met402Arg conferring higher resistance than SbmA_Gly254Glu, and SbmA_Gln361Leu. Chrome Azure S assays confirmed that these mutations, particularly FhuA_401Met402Arg insertions and SbmA_Gly254Glu, and SbmA_Gln361Leu substitutions, disrupt iron transport. Notably, FhuA mutants exhibited altered siderophore utilization, extracellular iron accumulation, enhanced biofilm formation (p < 0.05), increased flagellar motility (migration 1.7-2.7 cm), and attenuated virulence. In contrast, SbmA mutants showed broader metabolic remodeling and downregulated invasive virulence genes (prgI, invE), which correlates with enhanced in vivo virulence in mice. FhuA/SbmA mutations in S. typhimurium drive resistance, adaptive fitness, and pathogenicity through defined receptor-ligand interactions. This work provides a molecular framework for developing integrated antimicrobial approaches to mitigate the spread of resistant pathogens.

PMID:41519334 | DOI:10.1016/j.ijbiomac.2026.150111

Sci One Health. 2025 Oct 24;4:100132. doi: 10.1016/j.soh.2025.100132. eCollection 2025.

ABSTRACT

Emerging infectious diseases (EIDs), whether newly identified or re-emerging in human and animal populations, pose significant threats to global public health. China has experienced multiple EIDs outbreaks in recent years, underscoring the need for robust surveillance and early warning systems. Although China has established surveillance systems for events affecting climate, wildlife, livestock and poultry, and humans, the current systems remain inadequate for the early detection, monitoring, and prevention of zoonotic spillover events. The "One Health" approach, which integrates human, animal, and environmental health, offers a comprehensive strategy for mitigating EIDs risks. This study reviews China's national-level surveillance and early warning systems from a "One Health" perspective, highlighting key limitations and proposing future directions to enhance preparedness and response capabilities. The findings are intended to inform policy improvements and strengthen interdisciplinary collaboration for effective EIDs management.

PMID:41498121 | PMC:PMC12766100 | DOI:10.1016/j.soh.2025.100132

Vet Q. 2026 Dec;46(1):2607414. doi: 10.1080/01652176.2025.2607414. Epub 2026 Jan 5.

ABSTRACT

Bovine alphaherpesvirus 1 (BoHV-1) is the causative agent of infectious bovine rhinotracheitis and reproductive disorders causing significant economic losses in the cattle industry. Both BoHV-1 glycoproteins B (gB) and D (gD) are targets of neutralizing antibodies and desirable antigens for subunit vaccine. In this study, a bivalent subunit vaccine was generated based on the ectodomain of gD and gB expressed by baculoviruses system. Compared with the inactivated vaccine, the bivalent subunit vaccine induced higher neutralizing antibody levels against both the BoHV-1 reference strain and the virulent BoHV-1 field strain. Following intranasally challenge with BoHV-1 J2303, the clinical signs and virus excretion were significantly reduced in rabbits vaccinated with this subunit vaccine whereas severe clinical symptoms appeared in the non-vaccinated rabbits, indicating that the bivalent subunit vaccine provides complete protection against virulent BoHV-1 infection. Considering that the respiratory symptoms caused by J2303 in rabbits is highly similar and even identical to those of cattle, our findings suggest that the bivalent subunit vaccine based on combination of gD with gB protein have promising application to BoHV-1control programs.

PMID:41489934 | PMC:PMC12777838 | DOI:10.1080/01652176.2025.2607414

J Microbiol Biotechnol. 2025 Dec 15;35:e2510027. doi: 10.4014/jmb.2510.10027.

ABSTRACT

The 2009 pandemic H1N1 (pdm09) virus is both zoonotic and reverse-zoonotic, transmitting from swine to humans and vice versa. During the early zoonotic phase, immediately after the species jump and before substantial antigenic drift had accumulated, recombinant vaccine strains bearing hemagglutinin (HA) and neuraminidase (NA) from early pdm09 viruses often replicated poorly in embryonated chicken eggs (ECEs), contributing to delays and shortages in vaccine supply. Developing seed strains that are more productive in ECEs while preserving antigenicity and minimizing mammalian pathogenic potential is therefore essential for future pandemic preparedness. Efficient egg replication requires a balanced activity between HA and NA and their coordinated interaction with the polymerase subunit PB2. To this end, we generated PR8-derived recombinants combining PB2 backbones with distinct polymerase activities with targeted HA and NA modifications and edits to segment-specific 3' and 5' noncoding regions (NCRs). Comparative analysis of viral titers, together with sequence-based predictions of mutation effects, identified genotypes that improved replication in eggs while minimizing antigenic variations and reducing markers associated with mammalian virulence. Although further enhancement of viral yield is still warranted, these results delineate practical design principles, favoring balanced tuning of HA-NA functions, PB2 compatibility, and NCR context over large receptor-shift mutations, for engineering influenza seed strains. This work provides actionable guidance to support vaccine development and strengthen One-Health-oriented pandemic preparedness.

PMID:41407328 | PMC:PMC12723478 | DOI:10.4014/jmb.2510.10027

Virol J. 2025 Dec 7;23(1):9. doi: 10.1186/s12985-025-03035-8.

ABSTRACT

Newcastle Disease (ND) remains a major threat to poultry production worldwide, particularly in regions where it is endemic, like Southern Asia. The disease is caused by virulent forms of avian paramyxovirus-1, commonly termed Newcastle Disease Virus (NDV), a highly contagious virus with significant genetic diversity and evolving pathogenicity. This study aimed to molecularly characterize NDV isolates obtained from chickens and pheasants during the 2020/21 ND outbreaks in Nepal, to understand their genetic makeup, phylogenetic relationships, and implications for control strategies. Necropsy samples, including trachea, liver, intestine, spleen, lungs, heart, and proventriculus were collected from ten birds. Isolates from five clinical samples were typed as NDV by hemagglutination and hemagglutination inhibition (HA/HI) assays and were subjected to whole genome sequencing (WGS). Full genomes of 15,192 nucleotides were recovered from each isolate. Fusion (F) gene sequence analysis revealed the presence of multi-basic cleavage site motif ¹¹²RRQKRF¹¹⁷ in all isolates, indicative of virulent strain and suggesting a potentially velogenic or mesogenic phenotype. Phylogenetic analyses consistently classified all isolates within genotype VII.2 of class II NDV. Further comparative analysis indicated a close genetic relationship between the Nepalese isolates and strains reported from India and Bangladesh, and BEAST analysis suggested Southern Asia as the likely source of introduction into Nepal. These viral genomes provide additional insight into contemporary NDV circulating in an area of endemicity.

PMID:41354805 | PMC:PMC12798023 | DOI:10.1186/s12985-025-03035-8

J Vet Sci. 2025 Nov;26(6):e81. doi: 10.4142/jvs.25069.

ABSTRACT

IMPORTANCE: The Y439 lineage 01310 E20 H9N2 vaccine strain currently used in South Korea has undergone extensive egg adaptation, resulting in substantial changes, including an 18-amino acid neuraminidase (NA) stalk deletion. Additionally, both early and late 01310 passages inherently harbor an N-glycan at hemagglutinin (HA) residue 158-160 (HA158) that may interfere with virus-specific antibodies.

OBJECTIVE: We aimed to develop a high-yield vaccine strain without egg passaging and to overcome the limitations of the conventional vaccine strain that may compromise immunogenicity.

METHODS: We introduced a genetically modified 01310 PB2 gene (310-MVV: I66M, I109V, I133V) to increase replication in embryonated eggs and removed the N-glycan at HA158 and restored the NA stalk to improve immunogenicity. The resulting strain was assessed for egg replication and immunogenicity in chickens.

RESULTS: The resulting vaccine strain (310-SNS-193D-MVV) grew efficiently in embryonated eggs without repeated passaging. As restoring the NA stalk alone was insufficient to enhance NA-specific immunity, simultaneously removing the N-glycan at HA158 markedly increased NA-specific antibody responses and neutralizing antibody titers across multiple H9N2 lineages. Additionally, incorporating 310-SNS-193D-MVV into a bivalent formulation with a Y280 lineage strain conferred broader coverage without evidence of immune interference.

CONCLUSIONS AND RELEVANCE: These findings underscore how PB2, HA, and NA targeted genetic modifications can improve H9N2 vaccine productivity and immunogenicity. These strategies are not limited to our H9N2 strain and can be applied to other low propagating or NA stalk-deleted virus strains.

PMID:41332001 | PMC:PMC12703918 | DOI:10.4142/jvs.25069

Poult Sci. 2026 Jan;105(1):106108. doi: 10.1016/j.psj.2025.106108. Epub 2025 Nov 13.

ABSTRACT

Infectious bursal disease (IBD) remains one of the most important immunosuppressive diseases in poultry and has been endemic in China for over four decades. In recent years, outbreaks characterized by markedly reduced mortality have emerged. To investigate the current prevalence and pathogenicity of infectious bursal disease virus (IBDV), strains were isolated from vaccinated poultry farms in central and eastern China, and representative isolates of distinct genotypes were evaluated for pathogenicity. Phylogenetic analysis of segment A (HVR) and segment B (B-marker) classified segment A into eight genogroups (A1-A8), with A2 further divided into A2.1 and A2.2 and A3 into six subtypes (A3.1-A3.6). Segment B was grouped into four genogroups (B1-B4), with B3 and B4 subdivided into B3.1-B3.4 and B4.1-B4.2, respectively. The 23 isolates obtained were grouped into three genotypes: A2.2B1 (14/23, 60.9 %), A3.2B3.2 (8/23, 34.8 %), and A3.5B3.3 (1/23, 4.3 %). The A2.2B1 and A3.5B3.3 strains showed only minor amino acid substitutions relative to reference strains, whereas the newly emerged A3.2B3.2 genotype displayed substantial divergence. Pathogenicity evaluation in SPF chickens revealed no mortality after infection with SD/23 (A3.2B3.2), SHX/24 (A3.5B3.3), or WD/22 (A2.2B1). However, all three strains significantly reduced the bursa-to-body weight index (BBIX) to below 0.7 at 5 days post-inoculation and caused severe bursal atrophy. Histopathological examination showed medullary necrosis and lymphocyte depletion in the bursa following infection with SD/23 and SHX/24, closely resembling the lesions induced by WD/22. Moreover, SD/23 and SHX/24 displayed replication dynamics similar to those of the reference strain LX (A3.1B2), with elevated viral detection rates and high viral loads in multiple organs. In summary, multiple IBDV genotypes are co-circulating in China. Despite the reduced pathogenicity of circulating strains, diminished attention to subclinical infections may facilitate viral transmission and cause considerable economic losses.

PMID:41270549 | PMC:PMC12677167 | DOI:10.1016/j.psj.2025.106108

Front Cell Infect Microbiol. 2025 Oct 17;15:1682969. doi: 10.3389/fcimb.2025.1682969. eCollection 2025.

ABSTRACT

Over the past few decades, battery industry and electronic equipment have undergone explosive growth, but the heavy metal waste generated has led to significant global ecological and public health challenges. Currently, increasing evidences have confirmed the detrimental effects of heavy metal exposure on animal reproduction, immunity, and metabolism. However, research focused on the impacts of battery leakage on the gut microbiota remain scarce. Thus, this study aims to investigate the detrimental effects of battery on gut microbiota in chickens. Results revealed that battery exposure can lead to a significant increase in spleen index and a significant decrease in thymus index in chickens. Furthermore, battery exposure can significantly increase serum ALT, AST and MDA levels, and while concurrently reducing levels of GSH-Px and SOD. Battery exposure also cause a significant reduction in the gut microbial alpha diversity, accompanied by significant alterations in taxonomic composition. Bacterial taxonomic analysis indicated that the relative abundances of 1 phyla and 4 genera increased dramatically, while the relative abundance of 3 phylum and 115 genera decreased significantly during battery exposure. In conclusion, this study suggests that battery exposure leads to gut microbial dysbiosis and affect antioxidant ability in chickens. The significant alterations of gut microbiota may represent one of the mechanisms through which battery exerts its intestinal and renal toxicity. Given the context of battery pollutant leakage and inadequate recycling supervision, this study contributes to providing impetus for environmental protection agencies and organizations worldwide to enhance the recycling of battery waste.

PMID:41181318 | PMC:PMC12575344 | DOI:10.3389/fcimb.2025.1682969

Environ Res. 2025 Dec 15;287:123162. doi: 10.1016/j.envres.2025.123162. Epub 2025 Oct 20.

ABSTRACT

Emerging pesticides exposure in companion animals remains understudied despite growing concern over environmental contamination and pet health. We quantified 24 emerging pesticides and their metabolites in serum samples from 60 pet dogs and cats in Wuhan, China, using a salting-out assisted acetonitrile extraction method coupled with HPLC-MS/MS. A total of 19 compounds were detected in cats and 16 in dogs, with cats exhibiting significantly higher total pesticide concentrations (median: 4.90 ng/mL) than dogs (3.02 ng/mL). Organophosphates (OPs), particularly chlorpyrifos as indicated by its metabolite 3,5,6-trichloro-2-pyridinol (TCPY), were the predominant pesticide class in dogs, whereas pyrethroids (PYRs) and the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) were more abundant in cats. TCPY, 2,4-D and N-desmethyl acetamiprid (a neonicotinoid metabolite) were the most frequently detected pesticides across both species. Estimated daily intakes (EDIs) of these three dominant pesticides (0.0002-0.0649 μg/kg bw/day) were well below established chronic reference doses (cRfDs; 0.3-71 μg/kg bw/day), suggesting limited individual pesticide risk. However, over 95 % of serum samples contained multiple pesticide residues, raising concerns about potential cumulative and synergistic effect. These findings underscore the need for expanded biomonitoring efforts to better understand emerging pesticide exposure in pets and their role as sentinels for household and environmental chemical risks.

PMID:41125199 | DOI:10.1016/j.envres.2025.123162