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Department of Veterinary Medicine

Cambridge Veterinary School
 

Antimicrobial peptides in nematode secretions - Unveiling biotechnological opportunities for therapeutics and beyond

Fri, 28/03/2025 - 10:00

Biotechnol Adv. 2025 Mar 26:108572. doi: 10.1016/j.biotechadv.2025.108572. Online ahead of print.

ABSTRACT

Gastrointestinal (GI) parasitic nematodes threaten food security and affect human health and animal welfare globally. Current anthelmintics for use in humans and livestock are challenged by continuous re-infections and the emergence and spread of multidrug resistance, underscoring an urgent need to identify novel control targets for therapeutic exploitation. Recent evidence has highlighted the occurrence of complex interplay between GI parasitic nematodes of humans and livestock and the resident host gut microbiota. Antimicrobial peptides (AMPs) found within nematode biofluids have emerged as potential effectors of these interactions. This review delves into the occurrence, structure, and function of nematode AMPs, highlighting their potential as targets for drug discovery and development. We argue that an integrated approach combining advanced analytical techniques, scalable production methods, and innovative experimental models is needed to unlock the full potential of nematode AMPs and pave the way for the discovery and development of sustainable parasite control strategies.

PMID:40154760 | DOI:10.1016/j.biotechadv.2025.108572

Progressive evolution of <em>Streptococcus equi</em> from <em>Streptococcus equi</em> subsp. <em>zooepidemicus</em> and adaption to equine hosts

Fri, 28/03/2025 - 10:00

Microb Genom. 2025 Mar;11(3). doi: 10.1099/mgen.0.001366.

ABSTRACT

Streptococcus equi subsp. equi causes the equine respiratory disease 'strangles', which is highly contagious, debilitating and costly to the equine industry. S. equi emerged from the ancestral Streptococcus equi subsp. zooepidemicus and continues to evolve and disseminate globally. Previous work has shown that there was a global population replacement around the beginning of the twentieth century, obscuring the early genetic events in this emergence. Here, we have used large-scale genomic analysis of S. equi and its ancestor S. zooepidemicus to identify evolutionary events, leading to the successful expansion of S. equi. One thousand two hundred one whole-genome sequences of S. equi were recovered from clinical samples or from data available in public databases. Seventy-four whole-genome sequences representative of the diversity of S. zooepidemicus were used to compare the gene content and examine the evolutionary emergence of S. equi. A dated Bayesian phylogeny was constructed, and ancestral state reconstruction was used to determine the order and timing of gene gain and loss events between the different species and between different S. equi lineages. Additionally, a newly developed framework was used to investigate the fitness of different S. equi lineages. We identified a novel S. equi lineage, comprising isolates from donkeys in Chinese farms, which diverged nearly 300 years ago, after the emergence of S. equi from S. zooepidemicus, but before the global sweep. Ancestral state reconstruction demonstrated that phage-encoded virulence factors slaA, seeL and seeM were acquired by the global S. equi after the divergence of the basal donkey lineage. We identified the equibactin locus in both S. equi populations, but not S. zooepidemicus, reinforcing its role as a key S. equi virulence mechanism involved in its initial emergence. Evidence of a further population sweep beginning in the early 2000s was detected in the UK. This clade now accounts for more than 80% of identified UK cases since 2016. Several sub-lineages demonstrated increased fitness, within which we identified the acquisition of a new, fifth prophage containing additional toxin genes. We definitively show that acquisition of the equibactin locus was a major determinant in S. equi becoming an equid-exclusive pathogen, but that other virulence factors were fixed by the population sweep at the beginning of the twentieth century. Evidence of a secondary population sweep in the UK and acquisition of further advantageous genes implies that S. equi is continuing to adapt, and therefore, continued investigations are required to determine further risks to the equine industry.

PMID:40152912 | DOI:10.1099/mgen.0.001366

Isolation of phages infecting the zoonotic pathogen Streptococcus suis reveals novel structural and genomic characteristics

Tue, 25/03/2025 - 10:00

Microbiol Res. 2025 Mar 21;296:128147. doi: 10.1016/j.micres.2025.128147. Online ahead of print.

ABSTRACT

Bacteriophage research has experienced a renaissance in recent years, owing to their therapeutic potential and versatility in biotechnology, particularly in combating antibiotic resistant-bacteria along the farm-to-fork continuum. However, certain pathogens remain underexplored as targets for phage therapy, including the zoonotic pathogen Streptococcus suis which causes infections in pigs and humans. Despite global efforts, the genome of only one infective S. suis phage has been described. Here, we report the isolation of two phages that infect S. suis: Bonnie and Clyde. The phages infect 58 of 100 S. suis strains tested, including representatives of seven different serotypes and thirteen known sequence types from diverse geographical origins. Clyde suppressed bacterial growth in vitro within two multi-strain mixes designed to simulate a polyclonal S. suis infection. Both phages demonstrated stability across various temperatures and pH levels, highlighting their potential to withstand storage conditions and maintain viability in delivery formulations. Genome comparisons revealed that neither phage shares significant nucleotide identity with any cultivated phages in the NCBI database and thereby represent novel species belonging to two distinct novel genera. This study is the first to investigate the adhesion devices of S. suis infecting phages. Structure prediction and analysis of adhesion devices with AlphaFold2 revealed two distinct lineages of S. suis phages: Streptococcus thermophilus-like (Bonnie) and S. suis-like (Clyde). The structural similarities between the adhesion devices of Bonnie and S. thermophilus phages, despite the lack of nucleotide similarity and differing ecological niches, suggest a common ancestor or convergent evolution, highlighting evolutionary links between pathogenic and non-pathogenic streptococcal species. These findings provide valuable insights into the genetic and phenotypic characteristics of phages that can infect S. suis, providing new data for the therapeutic application of phages in a One Health context.

PMID:40132484 | DOI:10.1016/j.micres.2025.128147

Another step towards defeating meningitis

Fri, 14/03/2025 - 10:00

Lancet. 2025 Mar 11:S0140-6736(25)00196-5. doi: 10.1016/S0140-6736(25)00196-5. Online ahead of print.

NO ABSTRACT

PMID:40086455 | DOI:10.1016/S0140-6736(25)00196-5

Cell envelope polysaccharide modifications alter the surface properties and interactions of <em>Mycobacterium abscessus</em> with innate immune cells in a morphotype-dependent manner

Fri, 14/03/2025 - 10:00

mBio. 2025 Mar 14:e0032225. doi: 10.1128/mbio.00322-25. Online ahead of print.

ABSTRACT

Mycobacterium abscessus is one of the leading causes of pulmonary infections caused by non-tuberculous mycobacteria. The ability of M. abscessus to establish a chronic infection in the lung relies on a series of adaptive mutations impacting, in part, global regulators and cell envelope biosynthetic enzymes. One of the genes under strong evolutionary pressure during host adaptation is ubiA, which participates in the elaboration of the arabinan domains of two major cell envelope polysaccharides: arabinogalactan (AG) and lipoarabinomannan (LAM). We here show that patient-derived UbiA mutations not only cause alterations in the AG, LAM, and mycolic acid contents of M. abscessus but also tend to render the bacterium more prone to forming biofilms while evading uptake by innate immune cells and enhancing their pro-inflammatory properties. The fact that the effects of UbiA mutations on the physiology and pathogenicity of M. abscessus were impacted by the rough or smooth morphotype of the strain suggests that the timing of their selection relative to morphotype switching may be key to their ability to promote chronic persistence in the host.IMPORTANCEMultidrug-resistant pulmonary infections caused by Mycobacterium abscessus and subspecies are increasing in the U.S.A. and globally. Little is known of the mechanisms of pathogenicity of these microorganisms. We have identified single-nucleotide polymorphisms (SNPs) in a gene involved in the biosynthesis of two major cell envelope polysaccharides, arabinogalactan and lipoarabinomannan, in lung-adapted isolates from 13 patients. Introduction of these individual SNPs in a reference M. abscessus strain allowed us to study their impact on the physiology of the bacterium and its interactions with immune cells. The significance of our work is in identifying some of the mechanisms used by M. abscessus to colonize and persist in the human lung, which will facilitate the early detection of potentially more virulent clinical isolates and lead to new therapeutic strategies. Our findings may further have broader biomedical impacts, as the ubiA gene is conserved in other tuberculous and non-tuberculous mycobacterial pathogens.

PMID:40084888 | DOI:10.1128/mbio.00322-25

Infection by Clonally Related <em>Mycobacterium abscessus</em> Isolates: The Role of Drinking Water

Wed, 12/03/2025 - 10:00

Am J Respir Crit Care Med. 2025 Mar 12. doi: 10.1164/rccm.202409-1824OC. Online ahead of print.

ABSTRACT

RATIONALE: Mycobacterium abscessus group bacteria (MABS) cause lethal infections in people with chronic lung diseases. Transmission mechanisms remain poorly understood; the detection of dominant circulating clones (DCCs) has suggested potential for person-to-person transmission.

OBJECTIVES: This study aimed to determine the role of drinking water in the transmission of MABS.

METHODS: A total of 289 isolates were cultured from respiratory samples (231) and drinking water sources (58) across Queensland, Australia.

MEASUREMENTS AND MAIN RESULTS: Whole genome sequences were analysed to identify DCCs and determine relatedness. Half of the isolates (144, 49·8%) clustered with previously described DCCs, of which 30 formed a clade within DCC5. Pangenomic analysis of the water-associated DCC5 clade revealed an enrichment of genes associated with copper resistance. Four instances of plausible epidemiological links were identified between genomically-related clinical and water isolates.

CONCLUSIONS: We provide evidence that drinking water is a reservoir for MABS and may be a vector in the chain of MABS infection.

PMID:40072241 | DOI:10.1164/rccm.202409-1824OC

Canine genome-wide association study identifies <em>DENND1B</em> as an obesity gene in dogs and humans

Thu, 06/03/2025 - 11:00

Science. 2025 Mar 6:eads2145. doi: 10.1126/science.ads2145. Online ahead of print.

ABSTRACT

Obesity is a heritable disease, but its genetic basis is incompletely understood. Canine population history facilitates trait mapping. We performed a canine genome-wide association study for body condition score, a measure of obesity, in 241 Labrador retrievers. Using a cross-species approach, we showed canine obesity genes are also associated with rare and common forms of obesity in humans. The lead canine association was within the gene DENN domain containing 1B (DENND1B). Each copy of the alternate allele was associated with ~7% greater body fat. We demonstrate a role for this gene in regulating signaling and trafficking of melanocortin 4 receptor, a critical controller of energy homeostasis. Thus, canine genetics identified obesity genes and mechanisms relevant to both dogs and humans.

PMID:40048553 | DOI:10.1126/science.ads2145

Genome-wide association study of idiopathic epilepsy in the Italian Spinone dog breed

Wed, 05/03/2025 - 11:00

PLoS One. 2025 Mar 5;20(3):e0315546. doi: 10.1371/journal.pone.0315546. eCollection 2025.

ABSTRACT

Idiopathic epilepsy (IE) has a high prevalence and a severe clinical course in the Italian Spinone breed of dog. A genome-wide association study meta-analysis of 52 cases and 51 controls was conducted to identify genomic regions that may be involved with the development of IE. Subsequent to the meta-analysis, a set of 175 controls and an independent validation set of 23 cases and 23 controls were genotyped for SNPs showing suggestive association with IE to find variants exhibiting evidence of replicable association and to test the predictiveness of SNPs for IE status when combined in a weighted risk score. Although two regions showed statistically significant association with IE in the GWAS meta-analysis, and additional regions with suggestive association were identified, the findings were not emulated in the validation set. This is the first GWAS of IE in the Italian Spinone, and the findings suggest that IE in the breed is not monogenic and demonstrates the challenges when investigating a multigenic or complex inherited disease in a numerically small domesticated animal population.

PMID:40043055 | DOI:10.1371/journal.pone.0315546

Qualitative studies on farm managers perception of risk from HPAIV and implementation of biosecurity measures on UK poultry farms

Wed, 26/02/2025 - 11:00

Prev Vet Med. 2025 Feb 15;239:106445. doi: 10.1016/j.prevetmed.2025.106445. Online ahead of print.

ABSTRACT

The epidemic of high pathogenicity avian influenza (HPAI) H5N1 in the United Kingdom and Northern Europe from 2021 to 2023 has dwarfed all previous incursions. This fact has driven the need to review biosecurity behaviours and perceptions of virus incursions on commercial poultry farms. This study used qualitative methods to evaluate farm managers' perceptions of biosecurity and their implementation of measures as recommended by the Animal and Plant Health Agency (APHA). Thirteen farm managers across different regions of England and Wales were recruited between May and September 2023 to take part in the study. Qualitative semi-structured interviews were held with managers to discuss various topics relating to biosecurity and avian influenza (AI). Biosecurity measures being used across the farm by managers and staff were also observed to help understand biosecurity behaviours. Interviews were transcribed and analysed to identify themes and patterns amongst the data, along with extensive notes collated during the farm visits. Findings showed that farms' use of biosecurity with respect to disinfection regimes and use of foot dips were both well cited and observed. Similarly, farm managers were all highly likely to refer to the use of farm-specific and shed-specific rubber boots, while also citing stricter requirements for visitors and delivery/maintenance. Biosecurity concerning the layout of the premises, fencing, access to changing rooms and the general age and maintenance of buildings and sheds required significant improvement across many farms. Additionally, farm managers expressed strong feelings of stress and anxiety in recent years, particularly those who had experienced an AI outbreak recently. We argue that factors such as risk perceptions, remits of control, feelings of responsibility and autonomy, and consequences on mental health, are all factors that can inform how farm managers respond to outbreaks and implement or sustain biosecurity on farms. A greater emphasis on providing regular and tailored training and educational resources for the industry would be beneficial as would further services focusing on reducing the burden on farmers' mental health. This research provides insight into the application and shortcomings of biosecurity implementation on commercial poultry farms. It also identifies farmer perceptions and experiences shaping implementation on farms. However, this highlights that the onus for improving biosecurity cannot remain solely with farm managers and workers. Further research exploring the role of other stakeholders in the industry would help bridge remaining gaps in our understanding of biosecurity implementation.

PMID:40010002 | DOI:10.1016/j.prevetmed.2025.106445

Association of Serum Symmetric Dimethylarginine Concentrations and Inflammation in Cats

Wed, 26/02/2025 - 11:00

J Vet Intern Med. 2025 Mar-Apr;39(2):e70030. doi: 10.1111/jvim.70030.

ABSTRACT

BACKGROUND: Serum symmetric dimethylarginine (SDMA) concentrations are higher in some hyperthyroid cats with normal renal function, presumably due to increased protein catabolism.

OBJECTIVES: To investigate if SDMA is higher in cats with inflammation (defined as elevated serum amyloid A [SAA]).

ANIMALS: Twenty-eight cats: 12 with elevated SAA concentrations (> 3.9 μg/mL) and 16 with normal SAA.

METHODS: Retrospective case control study. Cats presenting to a referral institution between 2016 and 2022 with a documented SAA were identified. Individuals with renal and extrarenal factors known to affect SDMA were excluded. SDMA was measured from stored serum samples. Comparisons were made using the Mann-Whitney U test, and correlations assessed using Spearman's correlation coefficient. Data are presented as median [minimum-maximum].

RESULTS: SDMA was not significantly different between cats with elevated SAA and normal SAA (11 [5-17] μg/dL vs. 13 [9-21] μg/dL, respectively; p = 0.28). There was no correlation between SDMA and SAA (rs = -0.105; p = 0.594) or serum TT4 concentrations (rs = -0.023; p = 0.906). No difference in age or USG was present between elevated SAA and normal SAA groups (p = 0.908 and p = 0.165, respectively). Serum urea and creatinine concentrations were both significantly lower in cats with elevated SAA compared to those with normal SAA (6.3 [3.6-8.8] mmol/L vs. 8.4 [6.2-10.5] mmol/L; p = 0.008, and 96 [62-129] μmol/L vs. 118 [90-147] μmol/L; p = 0.008, respectively).

CONCLUSIONS AND CLINICAL IMPORTANCE: SDMA might be a more representative biomarker of GFR during inflammatory states, provided other confounding factors that affect SDMA are eliminated.

PMID:40008808 | DOI:10.1111/jvim.70030

Gross, cytological and histological features of a cholangiocarcinoma, with immunolabelling of cytokeratin 19, in a bronze-winged parrot (Pionus chalcopterus)

Wed, 19/02/2025 - 11:00

J Comp Pathol. 2025 Feb 18;217:62-65. doi: 10.1016/j.jcpa.2025.01.006. Online ahead of print.

ABSTRACT

An adult bronze-winged parrot (Pionus chalcopterus) was presented for post-mortem examination following death without antecedent clinical signs. Macroscopically, the liver was expanded by a 14 × 12 × 10 mm, off-white to grey, infiltrative mass with 3-8 mm diameter nodular masses on the serosa of the duodenum. Cytology of impression smears of the hepatic mass revealed a monomorphic population of epithelial cells, arranged in cohesive clusters, occasionally with an acinar-like arrangement. Histologically, the neoplasm was unencapsulated, infiltrative, well-demarcated and moderately densely cellular. Neoplastic cells were arranged in well-defined, variably sized acini and tubules that were supported by a fine collagenous stroma. Acini and tubules frequently contained intraluminal eosinophilic proteinaceous material. Neoplastic cells were small to moderately sized and were generally columnar or cuboidal with well-delineated cell boundaries and a small amount of eosinophilic to basophilic cytoplasm. The nuclei were round, frequently basally located and had densely stippled chromatin and usually a single, prominent, magenta nucleolus. There were two mitoses in 10 high-power fields (2.37 mm2). Vascular invasion was observed and metastatic nodules of similar neoplastic cells were present on the duodenal serosa. Immunohistochemical labelling for cytokeratin 19 revealed weak to moderate, punctate cytoplasmic expression in <10% of neoplastic cells. Macroscopically, cytologically and histologically the neoplasm was consistent with a cholangiocarcinoma.

PMID:39970837 | DOI:10.1016/j.jcpa.2025.01.006

Modelling the impact and cost effectiveness of universal varicella vaccination in England

Thu, 13/02/2025 - 11:00

Vaccine. 2025 Feb 12;50:126831. doi: 10.1016/j.vaccine.2025.126831. Online ahead of print.

ABSTRACT

INTRODUCTION: Two distinct diseases are attributable to the varicella zoster virus, varicella (chickenpox) and zoster (shingles). This study assesses the impact and cost-effectiveness of a childhood varicella vaccination program in England.

METHODS: We use an age-structured dynamic transmission model and a health economic decision tree. The model incorporates recent data on varicella and zoster epidemiology, including the effects of exogenous boosting on zoster incidence. By simulating various vaccination strategies, including routine and catch-up programs, the study evaluates the potential reduction in varicella and zoster cases due to vaccination and the associated vaccine cost-effectiveness (from the NHS perspective).

RESULTS: We find that a two-dose varicella vaccination program could significantly reduce varicella incidence, potentially achieving near-elimination if high coverage rates are maintained. However, the model also predicts a temporary increase in zoster incidence due to reduced natural boosting from varicella exposure; this is partly mitigated by the current zoster vaccination program and the effect is much less substantial than previously estimated. Cost-effectiveness analyses reveal that all vaccination strategies modelled are cost-effective at typical thresholds, with the routine vaccination scenario being the most economically advantageous. Sensitivity analyses demonstrate that vaccine price and varicella treatment costs are the primary drivers of cost-effectiveness.

CONCLUSION: The study supports the introduction of a childhood varicella vaccination program in England, which offers substantial health benefits and is highly likely to be cost-effective.

PMID:39946866 | DOI:10.1016/j.vaccine.2025.126831

Patient-specific Guides Improve the Accuracy and Safety of Transcondylar Screw Placement-a Cadaveric Study in the Canine Humerus

Tue, 11/02/2025 - 11:00

Vet Comp Orthop Traumatol. 2025 Feb 11. doi: 10.1055/a-2510-3720. Online ahead of print.

ABSTRACT

OBJECTIVES: The goal of this study was to compare the accuracy and safety of a transcondylar screw (TCS) placed using a 3D-printed patient-specific guide (PSG) or a generic aiming device (AD). We hypothesized that PSG is more accurate (i.e., positioning and orientation closer to the optimal trajectory) and safer (reduced incidence of joint violation) than the AD.

METHODS: A total of seven pairs of forelimbs were allocated to PSG and AD groups. After CT scanning, the optimal TCS orientation was planned in silico by a surgical specialist, and guides were printed. Using the PSG or AD, a 2.5-mm drill hole was drilled from medial to lateral across the humeral condyle. The positioning of the "planned" and "achieved" drill holes was defined on postoperative CT. The accuracy of TCS positioning and the risk of joint penetration were then calculated for the two groups.

RESULTS: Positioning of the entry and exit holes was significantly more accurate in the PSG group. Differences in screw angulation were not significantly different between groups. Despite the presence of an outlier (caused by incomplete seating of the PSG against the bone), 7 out of 7 screws positioned with PSG were "safe," while 3 out of 7 from the AD group would have violated the joint.

CONCLUSION: Our data confirm the technical superiority of PSG over the AD for placement of a TCS in the humeral condyle.

PMID:39933720 | DOI:10.1055/a-2510-3720

Bone marrow mesenchymal stromal cells support translation in refractory acute myeloid leukemia

Tue, 11/02/2025 - 11:00

Cell Rep. 2025 Jan 28;44(1):115151. doi: 10.1016/j.celrep.2024.115151. Epub 2024 Dec 28.

ABSTRACT

In acute myeloid leukemia (AML), malignant cells surviving chemotherapy rely on high mRNA translation and their microenvironmental metabolic support to drive relapse. However, the role of translational reprogramming in the niche is unclear. Here, we found that relapsing AML cells increase translation in their bone marrow (BM) niches, where BM mesenchymal stromal cells (BMSCs) become a source of eIF4A-cap-dependent translation machinery that is transferred to AML cells via extracellular vesicles (EVs) to meet their translational demands. In two independent models of highly chemo-resistant AML driven by MLL-AF9 or FLT3-ITD (internal tandem duplication) and nucleophosmin (NPMc) mutations, protein synthesis levels increase in refractory AML dependent on nestin+ BMSCs. Inhibiting cap-dependent translation in BMSCs abolishes their chemoprotective ability, while EVs from BMSCs carrying eIF4A boost AML cell translation and survival. Consequently, eIF4A inhibition synergizes with conventional chemotherapy. Together, these results suggest that AML cells rely on BMSCs to maintain an oncogenic translational program required for relapse.

PMID:39932190 | DOI:10.1016/j.celrep.2024.115151

Gut microbiota-derived hexa-acylated lipopolysaccharides enhance cancer immunotherapy responses

Mon, 10/02/2025 - 11:00

Nat Microbiol. 2025 Feb 10. doi: 10.1038/s41564-025-01930-y. Online ahead of print.

ABSTRACT

The gut microbiome modulates immunotherapy treatment responses, and this may explain why immune checkpoint inhibitors, such as anti-PD-1, are only effective in some patients. Previous studies correlated lipopolysaccharide (LPS)-producing gut microbes with poorer prognosis; however, LPS from diverse bacterial species can range from immunostimulatory to inhibitory. Here, by functionally analysing faecal metagenomes from 112 patients with melanoma, we found that a subset of LPS-producing bacteria encoding immunostimulatory hexa-acylated LPS was enriched in microbiomes of clinical responders. In an implanted tumour mouse model of anti-PD-1 treatment, microbiota-derived hexa-acylated LPS was required for effective anti-tumour immune responses, and LPS-binding antibiotics and a small-molecule TLR4 antagonist abolished anti-PD-1 efficacy. Conversely, oral administration of hexa-acylated LPS to mice significantly augmented anti-PD-1-mediated anti-tumour immunity. Penta-acylated LPS did not improve anti-PD-1 efficacy in vivo and inhibited hexa-acylated LPS-induced immune activation in vitro. Microbiome hexa-acylated LPS therefore represents an accessible predictor and potential enhancer of immunotherapy responses.

PMID:39929976 | DOI:10.1038/s41564-025-01930-y

Whole genome sequencing identifies novel candidate genetic variants in canine stomatocytosis

Mon, 10/02/2025 - 11:00

Gene. 2025 Feb 8:149314. doi: 10.1016/j.gene.2025.149314. Online ahead of print.

ABSTRACT

Stomatocytosis is a rare spectrum of red blood cell (RBC) disorders. In humans, stomatocytosis is typically caused by genetic changes in specific ion exchange and transport genes. Stomatocytosis has been identified in dogs, however the underlying genetic causes are unknown. Recently, stomatocytosis was reported in a Beagle and Australian Cattle Dog for the first time. Here, whole-genome sequencing (WGS) of these dogs was undertaken to identify candidate genetic variants driving or impacting stomatocytosis. Cases were compared to WGS of 119 controls of several breeds and > 1,000 dogs from public and private datasets. Candidate genes were identified, including genes linked to stomatocytosis in humans: SPTB and KCNN4. Notably, each case carried a different homozygous intronic SNP in SPTB only 24 bases apart (Beagle - chr8:39,194,923; ACD - chr8:39,194,947; CanFam3.1), which were not homozygous in other dogs. Variants with predicted deleterious impact in additional ion transport-related genes were also identified: SLC8A3, DYSF, SLC12A8, INPP5E, SLC1A1, and a novel SLC41A3 genetic change carried by the Australian Cattle Dog. Human and mouse scRNAseq and proteomics data indicate that these candidate genes are expressed in RBCs or their immature precursors. Taken together, these genetic data obtained from spontaneous stomatocytosis in a non-human species provides novel insights and candidate genes for evaluation of rare red cell disorders in humans.

PMID:39929273 | DOI:10.1016/j.gene.2025.149314

Comparative performance of tuberculin and defined-antigen cocktails for detecting bovine tuberculosis in BCG-vaccinated cattle in natural settings

Thu, 06/02/2025 - 11:00

Sci Rep. 2025 Feb 7;15(1):4564. doi: 10.1038/s41598-025-85389-1.

ABSTRACT

Bovine tuberculosis (bTB) is a threat to cattle health and public safety. The current control programs are hampered by wildlife reservoirs and socioeconomic barriers. Vaccinating cattle with Bacillus Calmette-Guérin (BCG) effectively reduces transmission, offering a potential solution for controlling bTB. A key requirement for vaccination strategies using BCG is the validation of defined antigens to differentiate infections among vaccinated animals (DIVA). We compared tuberculin with DIVA peptide cocktails (ESAT-6, CFP-10, and Rv3615c) in 67 unvaccinated and 67 BCG-vaccinated cattle exposed to M. bovis in a natural setting. The cattle were tested every 4 months with a skin test and every 2 months with interferon-gamma (IFN-γ) release assays (IGRA) over a year of exposure. Before exposure, the DIVA skin, DIVA IGRA, and tuberculin tests showed 100% specificity in unvaccinated control calves. After exposure, the DIVA skin, DIVA IGRA, and comparative cervical tuberculin (CCT) tests had comparable sensitivities of 46% (95% CI 36, 56), 45% (95% CI 35, 55), and 47 (95% CI 37, 57), respectively, when assessed against animals positive by M. bovis culture PCR. The results suggest that test-and-slaughter control strategies using tests with low sensitivity are not expected to be effective in controlling bTB in high-prevalence herds, and highlight an urgent need to improve the sensitivity of diagnostic tests for bTB in these settings.

PMID:39915566 | DOI:10.1038/s41598-025-85389-1

Identification of serotype O3b and high-risk clone ST37 of <em>Klebsiella pneumoniae</em> revealed by comparative genomic analysis

Tue, 04/02/2025 - 11:00

Front Cell Infect Microbiol. 2025 Jan 20;14:1517125. doi: 10.3389/fcimb.2024.1517125. eCollection 2024.

ABSTRACT

BACKGROUND: Epidemiological risk factors such as the demography of a place, environment, food, livestock, and companion animals are known sources of Klebsiella pneumoniae infection. Whole-genome sequencing (WGS) has become a powerful tool to complement traditional microbiological characterization of foodborne pathogens. Moreover, K. pneumoniae has several species complexes (KpSC) and is very difficult to differentiate using routine microbiological methods. The present study aims to investigate the prevalence of K. pneumoniae in fish available in the retail market using WGS.

METHODS: Isolation of K. pneumoniae, identification of K. pneumoniae isolates, and determination of the minimum inhibitory concentration (MIC) were performed. Whole-genome sequencing of K. pneumoniae genomes and phylogenomic analysis were conducted for visual comparison of the genomes. Furthermore, genomes of non-human origin that were submitted from India to the NCBI database were downloaded and included in the comparative analysis.

RESULTS: The findings showed that many antibiotic-resistant genes (ARGs) are prominent, including acrD, BaeR, cpxA, mdtB, mdtC, CRP, H-NS, KpnE, KpnF, KpnG, KpnH, acrA, acrB, marA, ramB, oqxA, oqxB, LptD, and emrR. Four fish-sourced isolates had different blaSHV resistance gene variants. The presence of ARGs for aminoglycosides [aac(3)-IId], fluoroquinolones (oqxA, oqxB), and fosfomycin (fosA5, fosA6) in these K. pneumoniae isolates from fish sources was found. One of the CIFT-K6 isolates had the uncommon serotype of K. pneumoniae O3b with the high-risk clone "ST37." The ST515 sequence type was present in two K. pneumoniae isolates (CIFT-K7 and CIFT-K8), but the O3b serotype and ST192 allele type were present in the CIFT-K10 isolate.

CONCLUSION: To the best of our knowledge, this research study represents the first Indian report of K. pneumoniae linked to fish, specifically the high-risk clone 'ST37' and two other STs, 515 and 192. The most common plasmid type detected in all four isolates was IncFIB, and 75% of the isolates were IncFII and IncHI1B. The prevalence of ARGs linked to efflux pump resistance mechanisms is highlighted by the analysis of genome sequence data.

PMID:39902187 | PMC:PMC11788149 | DOI:10.3389/fcimb.2024.1517125

Demography of the Gambian Epauletted Fruit Bat (<em>Epomophorus gambianus</em>) in Ghana

Fri, 31/01/2025 - 11:00

J Mammal. 2024 Sep 5;106(1):168-177. doi: 10.1093/jmammal/gyae096. eCollection 2025 Feb.

ABSTRACT

We provide the first estimates of survival and reproductive rates for a population of the Gambian Epauletted Fruit Bat Epomophorus gambianus in Ghana. We focused on a large colony of ca. 5,000 bats over 3 years to estimate population parameters including population size, birth rates, survival, and sex ratios for this species. Reproduction chronology was confirmed as seasonal bimodal polyestry, with births occurring in March/April and August/September each year. The estimated birth rate was 0.89 (95% CI = 0.85 to 0.92) per reproductive season. The overall sex ratio (female to male ratio) of the study population was male-dominated (0.69, 95% CI = 0.64 to 0.75), but female-biased for adults (62% female, χ2 1 = 42, P < 0.0001), and showed temporal and age-specific variations. By radiotracking 60 bats for 10 months, we obtained the first estimates of minimum monthly survival for this species as 0.81 (95% CI = 0.74 to 0.86), but this could be an underestimate due to possible undetected emigration of tagged bats.

PMID:39886213 | PMC:PMC11776427 | DOI:10.1093/jmammal/gyae096