Editorial: Sequencing technologies in advancing veterinary and zoonotic infection research.
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antimicrobial resistance↗
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Frequency of Human Brucellosis Complications in West Asia: A Systematic Review and Meta-Analysis.
BACKGROUND: Brucellosis is a multi-systemic zoonotic infection. The West Asia/Middle East region is an important global hotspot for brucellosis. This systematic review and meta-analysis aimed to aggregate and synthesize all the available evidence regarding the complications of brucellosis in West Asia/Middle East region. METHODS: PubMed, Embase, Scopus, Web of Science, Google Scholar, and Proquest were searched. Selection of studies, data extraction, and the risk of bias assessment were performed in duplicate. Data extraction was performed for 254 complications. Meta-analysis was performed using a random-effects model with Freeman-Tukey double arcsine transformation. Where applicable small-study effects was assessed using funnel plots and Egger's test. Separate by-country, by-age, and by-publication-decade subgroup analyses were performed if feasible. RESULTS: Out of 9518 results, 240 studies (260 references) were included. The majority of the included studies were conducted in Turkey (n = 177). The reported complications varied and different complication categorization systems were detected. The highest pooled estimate was observed for musculoskeletal involvement (50%, 95%CI: 39%-61%, I2 = 96.63%). The evidences is up-to-date until March 4, 2024. CONCLUSIONS: Some complications such as the complications of the eye were not reported in all the countries. Therefore, it's recommended to determine the relative frequency of those complications in regions without such reports. The pooled estimates of different complications of brucellosis were different. There's a need for the standardization of the reporting of the complications of brucellosis to achieve comparability between studies and across different regions.
Brucellosis↗
Unique growth and morphology properties of Clade 5 Clostridioides difficile strains revealed by single-cell time-lapse microscopy.
Clostridioides difficile is a gastrointestinal pathogen of both humans and agricultural animals and thus a major One Health threat. The C. difficile species consists of five main clades, with Clade 5 currently undergoing speciation from Clades 1-4. Clade 5 strains are highly prevalent in agricultural animals and can cause zoonotic infections, suggesting that these strains have evolved phenotypes that distinguish them from Clade 1-4 strains. Here, we compare the growth properties of Clade 5 strains to those of Clade 1-4 strains using anaerobic time-lapse microscopy coupled with automated image analysis. Our analyses indicate that Clade 5 strains grow faster and are more likely to form long chains of cells than Clade 1-4 strains. Using comparative genomic and CRISPRi analyses, we show that the chaining phenotype of Clade 5 strains is driven by the orientation of the invertible cmr switch sequence, with chaining strains exhibiting a bias to the cmr-ON state. Interestingly, Clade 5 strains with a bias towards the cmr-ON state shifted to a largely cmr-OFF state during murine infection, suggesting that the cmr-OFF state is under positive selection during infection. Collectively, our data reveal that Clade 5 strains have distinct growth properties, which may allow them to inhabit diverse ecological niches.
Journal Article↗
First Fatal Case of Adult Meningoencephalitis Caused by Pasteurella canis: An Autopsy Case Report.
Pasteurella canis is a Gram-negative bacterium commonly found as a commensal organism in the oral cavity of dogs and cats. Human infections are rare and typically occur following skin breaches, with bacteremia reported less frequently. To date, fatal central nervous system infections in adults caused by P. canis have not been reported. We report the case of a 25-year-old immunocompetent man with no significant medical history. The patient developed otitis a few days after his dog licked his ear. Twenty days later, he died at home following a febrile illness with headaches. An autopsy revealed purulent meningitis. Bacteriological cultures from the ear and subdural empyema isolated P. canis and Streptococcus anginosus group. To our knowledge, this is the first reported case of fatal adult meningoencephalitis caused by P. canis. The case highlights the pathogen's invasive potential and underscores the importance of prompt evaluation of otitis with neurological involvement.
Humans↗
Unique growth and morphology properties of Clade 5 Clostridioides difficile strains revealed by single-cell time-lapse microscopy.
Clostridioides difficile is a gastrointestinal pathogen of both humans and agricultural animals and thus a major One Health threat. The C. difficile species consists of five main clades, with Clade 5 currently undergoing speciation from Clades 1-4. Since Clade 5 strains are highly prevalent in agricultural animals and a frequent cause of zoonotic infections, these strains may have evolved phenotypes that distinguish them from Clade 1-4 strains. Here, we compare the growth properties of Clade 5 strains to those of Clade 1-4 strains using anaerobic time-lapse microscopy coupled with automated image analysis. Our analyses indicate that Clade 5 strains grow faster and are more likely to form long chains of cells than Clade 1-4 strains. Using comparative genomic and CRISPRi analyses, we show that the chaining phenotype of Clade 5 strains is driven by the orientation of the invertible cmr switch sequence, with chaining strains exhibiting a bias to the cmr-ON state. Interestingly, Clade 5 strains with a bias towards the cmr-ON state shifted to a largely cmr-OFF state during murine infection, suggesting that the cmr-OFF state is under positive selection during infection. Collectively, our data reveal that Clade 5 strains have distinct growth properties, which may allow them to inhabit diverse ecological niches.
Clostridioides difficile↗
Multiple introductions of equine influenza virus into the United Kingdom resulted in widespread outbreaks and lineage replacement.
Influenza A viruses (IAVs) are prime examples of emerging viruses in humans and animals. IAV circulation in domestic animals poses a pandemic risk as it provides new opportunities for zoonotic infections. The recent emergence of H5N1 IAV in cows and subsequent spread over multiple states within the USA, together with reports of spillover infections in humans, cats and mice highlight this issue. The horse is a domestic animal in which an avian-origin IAV lineage has been circulating for >60 years. In 2018/19, a Florida Clade 1 (FC1) virus triggered one of the largest epizootics recorded in the UK, which led to the replacement of the Equine Influenza Virus (EIV) Florida Clade 2 (FC2) lineage that had been circulating in the country since 2003. We integrated geographical, epidemiological, and virus genetic data to determine the virological and ecological factors leading to this epizootic. By combining newly-sequenced EIV complete genomes derived from UK outbreaks with existing genomic and epidemiological information, we reconstructed the nationwide viral spread and analysed the global evolution of EIV. We show that there was a single EIV FC1 introduction from the USA into Europe, and multiple independent virus introductions from Europe to the UK. At the UK level, three English regions (East, West Midlands, and North-West) were the main sources of virus during the epizootic, and the number of affected premises together with the number of horses in the local area were found as key predictors of viral spread within the country. At the global level, phylogeographic analysis evidenced a source-sink model for intercontinental EIV migration, with a source population evolving in the USA and directly or indirectly seeding viral lineages into sink populations in other continents. Our results provide insight on the underlying factors that influence IAV spread in domestic animals.
Animals↗
Chromosome-Scale Genome of Zoonotic Eyeworm Thelazia callipaeda from China.
Thelazia callipaeda is a vector-borne zoonotic eyeworm infecting companion animals, wildlife, and humans, but chromosome-scale genomic resources from Chinese clinical material remain limited. We generated a genome supported by Pacific Biosciences (PacBio) high-fidelity (HiFi) sequencing and high-throughput chromosome conformation capture (Hi-C) from 100 adult worms recovered from naturally infected dogs in Beijing and compared its chromosome-scale organization with Portuguese assembly GCA_965194785.1. The final assembly spans 119.53 megabases (Mb) and comprises 115 top-level sequences, including four pseudomolecules totaling 91.26 Mb (76.34%) and 111 unanchored sequences. Genome-mode Benchmarking Universal Single-Copy Orthologs (BUSCO) analysis recovered 98.5% complete chromadorean orthologues, and the representative 11,788-protein gene set recovered 92.6%. Sequence-level alignment resolved Chinese chromosomes 1-4 (chr1-chr4) to Portuguese chr1, chrX, chr3, and chr2, respectively, with retained alignments covering 95.9-99.2% of each Chinese pseudomolecule and estimated sequence identities of 99.75-99.91%. Strong chromosome-scale collinearity was accompanied by localized reverse-collinear regions, including 0.243 Mb and 0.115 Mb intervals on chr2-chrX and chr3-chr3. The anchored sequences contained 96.7% of predicted genes and were substantially more gene-dense than the unanchored sequences. These results establish a clinically sourced Chinese chromosome-scale reference and provide a validated framework for future individual-worm, population-genomic, structural-variation, and comparative genomic studies of this parasite.
Hi-C↗
Leptospira-host interactions: advancing next-generation vaccines and diagnostics.
SUMMARYLeptospirosis, a widespread zoonotic disease caused by pathogenic Leptospira species, remains a major public health challenge, particularly in tropical and subtropical regions. Despite advances in understanding Leptospira biology and pathogenesis, effective disease control continues to be limited by the lack of rapid, early diagnostics, and broadly protective vaccines. This review comprehensively examines recent progress in deciphering Leptospira-host interactions, with emphasis on key virulence factors, immune-evasion mechanisms, and host immune responses that influence disease outcomes. Particular focus is placed on the molecular and cellular basis of adhesion, invasion, immune modulation, and persistent colonization. We further discuss the limitations of current vaccines and diagnostic approaches, and highlight how emerging technologies, including pan-genomics, proteomics, reverse vaccinology, immunoinformatics, and omics-based antigen discovery, are facilitating the development of next-generation vaccines and diagnostics. Finally, we outline major translational challenges and future perspectives for improving clinical management, surveillance, and prevention of leptospirosis. The concepts discussed in this review may also provide broader insights into vaccine and diagnostic development for other zoonotic bacterial infections.
Humans↗
Autoantibodies against type I interferons in patients with zoonotic H7N9 influenza: an observational case-control study.
BACKGROUND: The determinants of the species barrier preventing human infections with avian influenza A viruses (IAV) are incompletely understood. We previously identified loss-of-function variants of the interferon-regulated antiviral factor MxA as a genetic factor for increased susceptibility to infections with the H7N9 subtype. Given the central role of type I IFNs (IFN-I) in antiviral defence, we hypothesised that IFN-I-neutralising autoantibodies may similarly predispose to zoonotic H7N9 infection. METHODS: In this observational case-control study, serum samples collected between 2013 and 2017 from 199 Chinese patients with laboratory-confirmed H7N9 infection and 531 healthy, uninfected controls (269 poultry workers, 262 close contacts) were screened for IgG autoantibodies binding IFNα2, IFNβ1b, or IFNω using a multiplex bead-based assay. Positive samples were tested for IFN-neutralising activity in a luciferase-based reporter assay. To confirm their ability to block IFNα2-mediated antiviral activity, selected samples (n = 19) were analysed in IAV infection experiments. Associations between age, sex, H7N9 case status, case fatality, and the presence of neutralising autoantibodies were evaluated by logistic regression. Available whole-genome sequencing data from 26 individuals with neutralising autoantibodies were screened for variants in genes linked to IFN-I autoimmunity. FINDINGS: Neutralising autoantibodies against at least one IFN-I were detected in 19.1% (38/199) of patients but in only 1.1% (6/531) of controls, consistent with published general population data. Most patient sera targeted IFNα2 and/or IFNω (35/199), and 18.1% (36/199) neutralised even high IFN-I concentrations of 1-10 ng/ml. The presence of neutralising autoantibodies was associated with 8.2- to 25.3-fold higher odds of H7N9 infection (p < 0.0001), depending on antibody specificity and reference group. Autoantibody prevalence increased significantly with age in patients (44.8% ≥70 years; OR = 1.05; 95% CI 1.02-1.07; p = 0.0001), but was not associated with sex (OR for males vs. females = 0.52; 95% CI 0.23-1.14; p = 0.106). All selected sera containing neutralising autoantibodies blocked IFNα2-induced antiviral activity in cell culture. No known genetic predisposition for IFN-I autoimmunity was identified. INTERPRETATION: Our findings suggest that IFN-I-targeting autoimmunity is associated with susceptibility to zoonotic IAV infection with the H7N9 subtype, and possibly also other subtypes, including panzootic H5N1. Given the ease of implementation, screening for anti-IFN-I autoantibodies could be readily integrated into surveillance or targeted testing. This could be relevant in environments with increased exposure to zoonotic IAVs. FUNDING: Shenzhen Medical Research Fund, National Natural Science Foundation of China, Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences, Guangdong Provincial Science and Technology Program, Program for Youzuzhikeyan of Shenzhen University, German Research Foundation, Swiss National Science Foundation.
Humans↗
Investigating the zoonotic origins of ESBL-producing E. coli in community-acquired urinary tract infections in Ecuador.
Extended-spectrum β-lactamase-producing Escherichia coli (ESBL-producing E. coli) pose a growing global health threat. Although Latin America has been identified as a global hotspot of antimicrobial resistance, the zoonotic contribution to drug-resistant infections in the region remains poorly defined. We analyzed 137 clinical ESBL-producing E. coli isolates from urinary tract infections (UTIs) in Quito, Ecuador, applying a Bayesian latent class model informed by host-associated mobile genetic elements to estimate the fraction of infections attributable to food-animal sources. We estimated that 25.5% (35/137) of UTI isolates were putative zoonotic cases. This proportion rose to 42.5% after excluding ST131-H30, a human-associated pandemic lineage. Putative zoonotic isolates were enriched for animal-associated β-lactamase genes (e.g., blaTEM-1B, blaCTX-M-65), lacked human-associated markers such as blaOXA-1, and exhibited diverse antimicrobial resistance gene profiles resembling those observed among food-animal isolates. These isolates were also enriched for ColV-associated virulence genes typically linked to avian pathogenic E. coli. Putative zoonotic strains contributed substantially to third-generation cephalosporin-resistant UTIs in Quito, Ecuador, challenging assumptions derived from high-income settings that such infections are driven predominantly by human-to-human transmission. These findings highlight the importance of integrated One Health surveillance and mitigation, particularly in low- and middle-income countries where gaps in water, sanitation, and hygiene (WASH) may interact with antimicrobial use in food production to amplify antimicrobial resistance transmission.IMPORTANCEESBL-producing E. coli have rapidly emerged as a major global antimicrobial resistance threat. In Latin America, cephalosporins are commonly used in food-animal production, fueling the emergence of ESBL-producing E. coli. In low- and middle-income countries, excessive antimicrobial use driven by poorly regulated over-the-counter sales, combined with inadequate water, sanitation, and hygiene (WASH) infrastructure, can facilitate antimicrobial-resistant pathogen transmission from food animals to humans. Using a novel statistical-genomic approach, we found that over one in four cephalosporin-resistant UTIs in Quito, Ecuador, may be caused by E. coli strains originating from food animals. Our findings highlight the public health risks associated with antimicrobial use in food-animal production and the role of environmental and infrastructure-related vulnerabilities. As global demand for animal protein continues rising in middle-income countries, controlling zoonotic antimicrobial resistance transmission becomes increasingly urgent for protecting human health through integrated One Health strategies.
ESBL-producing E. coli↗
The agroenvironmental-clinical link of Proteus mirabilis: Genomic epidemiology, clonal relationships, and shared resistance and virulence profiles.
Proteus mirabilis is an opportunistic pathogen frequently associated with urinary tract infections (UTIs), with its pathogenicity driven by coordinated virulence traits such as adhesion, biofilm formation, and toxin production. The systemic emergence of antimicrobial resistance (AMR) within this species raises critical concerns regarding its persistence across clinical and environmental niches. This study investigated the virulence profiles, AMR determinants, and molecular epidemiology of P. mirabilis isolates recovered from retail vegetables and human community-acquired UTIs (CA-UTIs) in southern Brazil. A total of 310 isolates were analyzed (110 from vegetables and 200 from UTIs). Multidrug resistance was observed in 36.6-42.0% of vegetable isolates and 16.0% of UTI isolates, while extended-spectrum β-lactamase (ESBL) production reached 32.0% in the vegetable group. Notably, the carbapenemase gene blaKPC-2 was identified in vegetable isolates, representing a critical food safety concern. High-consequence resistance genes, including blaCTX-M variants, fosA3, and qnrD, were widely distributed. Furthermore, all isolates harbored multi-element virulence profiles-particularly genes encoding fimbriae, proteases, and iron acquisition systems-and exhibited strong or very strong biofilm-forming phenotypes. Clonal analysis revealed tight genetic relatedness between vegetable and clinical isolates, including indistinguishable profiles. Whole-genome sequencing identified shared sequence types (STs), most notably the high-risk clone ST773, alongside internationally reported lineages such as ST135 and ST336. Moreover, conserved mobile genetic environments flanking blaKPC-2 were structurally characterized. These findings demonstrate that food-associated P. mirabilis serves as an active agroenvironmental reservoir for virulent and multidrug-resistant lineages, posing an unmonitored risk for zoonotic dissemination and human infection within the One Health framework.
bla KPC−2↗
Development and application of a novel beta-tubulin genotyping tool reveals host-specific transmission cluster in Balantioides coli.
Balantioides coli is a zoonotic ciliated protozoan that infects humans and other mammals. Conventional and ITS-based genotyping approaches have limitations that hinder precise molecular epidemiological investigations. The objective of this study was to develop a new β-tubulin gene-based approach to enhance the detection and genotyping of B. coli. We performed single-cell isolation and whole-genome sequencing on two B. coli isolates from pigs and two from guinea pigs. We then used the β-tubulin gene sequences to design PCR primers for the new genotyping assay. We validated the assay using 56 ITS-confirmed B. coli-positive fecal DNA samples from pigs, cattle, sheep, and guinea pigs. Phylogenetic analyses were conducted using both β-tubulin and ITS sequences. The β-tubulin-based nested PCR assay exhibited 100% detection efficiency and greater specificity than ITS-based methods. Phylogenetic analysis of the β-tubulin gene sequences classified B. coli into three genotypes (I-III). Genotype III appears to be specific to guinea pigs. Genotypes I and II were found across multiple hosts, indicating potential cross-species transmission. Of the five full-length B. coli β-tubulin sequences obtained in this study, 264 polymorphic sites (19.8%) were identified, including both synonymous and non-synonymous mutations. Frequent recombination events within the β-tubulin locus were detected, indicating substantial genetic diversity. Therefore, the β-tubulin gene is a robust marker for genotyping and epidemiological studies of B. coli. The novel nested PCR assay overcomes the limitations of ITS-based methods and has produced data revealing previously unrecognized genetic diversity and host specificity patterns of B. coli.
Tubulin↗
Triacylglycerol metabolism is a novel target to combat West Nile virus infection.
West Nile virus (WNV) is a zoonotic Orthoflavivirus transmitted by mosquitoes that is responsible for outbreaks of meningitis and encephalitis worldwide. Driven by climate change, WNV has expanded as a global public health concern, particularly in temperate regions. However, there are still no specific approved therapies, reinforcing the need for antiviral development. Previous works have documented that WNV multiplication strictly depends on certain cellular lipids. To identify novel lipid-related therapeutic targets, we analyzed the infection driven alterations in the CNS lipidome, the primary tissue supporting WNV replication. Our results indicated that the major alterations in the brain lipid content of WNV-infected mice corresponded to triacylglycerols (TAGs). Moreover, transcriptomic analysis showed that infected brains underwent changes in the expression of TAG metabolism. Supplementation with exogenous fatty acids increased lipid droplets (LD) content and promoted viral replication in cell culture models. On the contrary, pharmacological intervention in TAG metabolism using diacylglycerol acyltransferase inhibitors (DGATi) suppressed WNV multiplication in cell culture models. As a proof-of-concept of the therapeutic potential of DGATi, treatment of mice with A922500 reduced viral burden in the brain and proinflammatory cytokine production. Overall, our results unveil the importance of LDs and glycerolipid metabolism for WNV and highlight the potential of therapeutic interventions targeting this pathway to control viral replication and neuroinflammation.
West Nile virus; lipid↗
Plasmodium knowlesi can adapt to infect Duffy-negative erythrocytes.
Plasmodium knowlesi, a zoonotic malaria species, has become a significant public health concern in Southeast Asia. In regions such as Malaysia and southern Thailand, P knowlesi incidence has risen, even as other human malaria parasites are nearing elimination. Similar to its close relative Plasmodium vivax, P knowlesi relies on the Duffy antigen receptor for chemokine (DARC) as a key receptor for erythrocyte invasion. Only Duffy-positive individuals are thought to be susceptible to clinical infection. Here, we demonstrate that P knowlesi possesses greater invasion plasticity than previously recognized. This parasite can bypass the need for DARC, as shown by its in vitro adaptation to invade and replicate within Duffy-negative (Fy-) erythrocytes. This adaptation is stable and independent of DARC binding, enabling the adapted parasite line to be maintained in Fy- erythrocytes and to resist inhibition by α-DARC antibodies. Genomic analysis identified a genomic recombination event between the parasite's dbpα and dbpγ genes, resulting in a new chimeric gene dbpαγ. Using CRISPR-Cas9 targeted reversion, we could demonstrate that dbpαγ is essential for invasion of Fy- erythrocytes. These findings shed new light on the invasion plasticity of P knowlesi, with implications for the parasite's potential spread beyond Southeast Asia and for understanding the complex host-cell specificity and atypical invasion pathways seen in P vivax.
Plasmodium knowlesi↗
Prevalence of Erysipelothrix rhusiopathiae in tonsils of domestic pigs and wild boars in Sweden.
Erysipelothrix rhusiopathiae (ER) causes erysipelas in multiple animal species and may persist in the environment or be carried asymptomatically. It is estimated that 30-50% of apparently healthy or convalescent pigs harbour ER in their tonsils and other lymphoid tissues. This study aimed to determine the prevalence of ER in the tonsils of healthy Swedish fattening pigs and wild boars. Tonsils were collected from 200 fattening pigs at slaughter from ten abattoirs across Sweden in 2017, with one pig per herd sampled. Wild boars (n = 180) were sampled during hunting, primarily in Östergötland County, in 2018. Cultures were performed using selective media and isolates were confirmed as ER by MALDI-TOF MS. ER was recovered from 6/200 pig tonsils (3.0%), all originating from three abattoirs in southern Sweden. ER was isolated from 76/167 (45.5%) of wild boar tonsils. Whole-genome sequencing revealed a high genetic diversity among the isolates with no dominant clones. Overall, these results indicate that Swedish pig husbandry, characterized by indoor rearing of fattening pigs, age-segregated rearing, sow vaccination, enhanced biosecurity, and restricted straw access largely prevents tonsillar colonization by ER aligning with the low occurrence of clinically diagnosed erysipelas in such herds. For wild boars, the high isolation rate suggests that wild boar could act as a reservoir and potential source of infection for domestic pigs. The potential zoonotic risk should also be considered.
Animals↗
Whole-Genome Sequencing of Feline Uropathogens Reveals Multidrug Resistance and Zoonotic Potential in Domestic Cats in Tunisia.
BACKGROUND: Urinary tract infections (UTIs) in cats are increasingly recognized as clinically relevant conditions frequently associated with multidrug-resistant (MDR) bacteria of potential zoonotic origin, yet genomic data on feline uropathogens remain scarce in Tunisia. METHODS: We used whole-genome sequencing to characterize seven bacterial isolates recovered from six cats with clinical signs of UTI: Mammaliicoccus lentus (n = 2), Staphylococcus schleiferi (n = 1), Mammaliicoccus sciuri (n = 1), Enterococcus faecalis (n = 1), Enterococcus casseliflavus (n = 1), and Klebsiella aerogenes (n = 1). RESULTS: Resistome analysis revealed determinants conferring resistance to β-lactams (blaZ, blaCMY-132), methicillin (mecC-type), macrolides (erm(43), ermB), tetracyclines (tet(M), tet(45), tetB), fosfomycins (fosI, fosB, fosA5), and aminoglycosides (aac(6'), aph(3')-IIIa, aph(6)-Id), alongside efflux pump genes (efrA, sepA, sdrM, oqxA, KpnE/F/G), vancomycin-operon genes (vanT, vanY, vanC, vanG), and biofilm/biocide-tolerance genes (salB, qacG). Notably, M. lentus S104 carried mecC-type elements, the first such report in Tunisia, while K. aerogenes displayed an extensive MDR profile, including blaCMY-132 and fosA5. Multilocus sequence typing/ribosomal multilocus sequence typing (MLST/rMLST) identified diverse lineages, including the internationally distributed E. faecalis ST19 and the rarely reported K. aerogenes ST242. Plasmids were absent in all isolates; a Tn916/1545-type transposon occurred in E. casseliflavus, and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems were unevenly distributed. CONCLUSIONS: These findings highlight companion animals as reservoirs of clinically important resistance genes, reinforcing the need for One Health AMR surveillance.
Animals↗
Viral zoonosis and human cancer: a perspective.
Zoonotic viruses, which are pathogens naturally transmitted from animals to humans, pose a significant and evolving challenge to public health. Although most known zoonotic viruses do not exhibit the persistence typically necessary for viral oncogenesis, the potential cancer-causing effects of these infections remain unclear. Persistent infection, latency, or abortive replication within susceptible but non-permissive human cells may allow some animal-origin viruses to evade immune clearance, disrupt host cell signaling, and induce genomic instability-key features of cancer development. Evidence from both in vitro and in vivo studies indicates that certain animal viruses can enter human cells, integrate their genetic material, or express oncogenic proteins, even without completing full replication. These mechanisms resemble those of established human oncoviruses and suggest that, under specific host and environmental conditions, zoonotic viruses could contribute to neoplastic transformation. Given the increasing frequency of human-animal interactions through companionship, agriculture, wildlife trade, and food production, multidisciplinary research combining virology, oncology, and epidemiology is essential. Such efforts should focus on sensitive molecular detection, mechanistic studies, and population-based investigations to better understand the long-term cancer risks associated with zoonotic viral infections and to guide effective prevention strategies.
Cancer↗
Candidate biomarkers for early Giardia duodenalis infection revealed by time-resolved secretome proteomics.
Giardia duodenalis is a zoonotic protozoan parasite that causes giardiasis in humans and other mammals. Early diagnosis remains challenging because current diagnostic methods, including microscopy and enzyme-linked immunosorbent assays (ELISAs), primarily detect established infections. Consequently, a critical diagnostic gap exists during the early stage of infection within the first 2-48 h following exposure. To address this limitation, we characterized the proteins released by in vitro-cultured G. duodenalis trophozoites under serum-free conditions and evaluated their potential as early diagnostic biomarkers. Proteomic analysis of culture supernatants collected during early trophozoite incubation identified 31,773 peptides corresponding to 2504 quantifiable proteins. Temporal profiling showed distinct secretion patterns, including proteins that peaked during the early stage, progressively accumulated over time, or remained persistently abundant throughout the incubation period. Based on their secretion characteristics and predicted immunogenic properties, five candidate biomarkers were selected for further evaluation. Polyclonal antibodies raised against selected candidates successfully detected the corresponding proteins in serum-free culture supernatants, providing preliminary evidence for their potential utility as early-stage diagnostic targets. These findings identify stage-associated candidate proteins that may serve as a resource for future early giardiasis diagnostic development, provide a valuable resource for investigating host-parasite interactions, and establish a foundation for future diagnostic assay development. However, further validation in clinical and biological samples is required to confirm their diagnostic applicability. SIGNIFICANCE: Giardiasis, caused by Giardia duodenalis, is a major diarrheal disease worldwide. Although enzyme-linked immunosorbent assays (ELISAs) provide rapid detection, their diagnostic utility is limited by the lack of biomarkers capable of identifying infection during its earliest stages, creating a critical gap in the detection of active infection within 2-48 h following exposure. Using data-independent acquisition proteomics, this study provides a time-resolved characterization of proteins released by G. duodenalis trophozoites into serum-free culture supernatants. Our findings reveal temporal secretion dynamics of protein secretion and identify candidate biomarkers with potential utility for the development of early-stage diagnostic assays pending rigorous biological and clinical validation. In addition, this proteomic resource provides a foundation for investigating host-parasite interactions and may facilitate the development of future point-of-care diagnostic strategies.
Giardiasis↗