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Cell Rep. 2025 Feb 25;44(2):115263. doi: 10.1016/j.celrep.2025.115263. Epub 2025 Feb 7.

ABSTRACT

Appropriate cellular recognition of viruses is essential for the generation of an effective innate and adaptive immune response. Viral sensors and their downstream signaling components thus provide a crucial first line of host defense. Many of them exhibit subcellular relocalization upon activation, resulting in the expression of interferon and antiviral genes. To comprehensively identify signaling factors, we analyzed protein relocalization on a global scale during viral infection. cAMP-responsive element-binding protein (CREB)-regulated transcription coactivators 2 and 3 (CRTC2/3) exhibited early cytoplasmic-to-nuclear translocation upon infection with multiple viruses in diverse cell types. This movement was dependent on mitochondrial antiviral signaling protein (MAVS), cyclo-oxygenase proteins, and protein kinase A. A key effect of CRTC2/3 translocation is transcription of the fibro-inflammatory cytokine interleukin (IL)-11. This may be important clinically in viral infections associated with fibrosis, including SARS-CoV-2. Nuclear translocation of CRTC2/3 is, therefore, identified as an important pathway in the context of viral infection.

PMID:39921859 | DOI:10.1016/j.celrep.2025.115263

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 | PMC:PMC11802902 | DOI:10.1038/s41598-025-85389-1

PLoS Pathog. 2025 Feb 5;21(2):e1012924. doi: 10.1371/journal.ppat.1012924. eCollection 2025 Feb.

ABSTRACT

A better understanding of the system-level effects of antibiotics on bacterial cells is essential to address the growing challenge of antibiotic resistance. Utilising Multipad Agarose Plate (MAP) platforms, we monitor the growth rate and cell morphology of three clinically relevant species (E.coli, S.aureus and P.aeruginosa) following exposure to 14 antibiotics across 11 concentrations (31 microbe-antibiotic combinations in total). Our results reveal a consistent increase in population growth rate heterogeneity (PGRH) as drug concentrations approach the minimum inhibitory concentration (MIC). Strikingly, the magnitude of this heterogeneity correlates with the functional distance between the ribosome and the specific cellular processes targeted by the antibiotics. Among the seven antibiotic classes studied, protein synthesis inhibitors and disruptors cause the lowest PGRH, while heterogeneity progressively increases with RNA synthesis inhibitors, DNA replication inhibitors, cell membrane disruptors and cell wall synthesis inhibitors. Because the ribosome is central to growth rate control, we hypothesize that heterogeneity might arise at the system level as a result of the propagation of damage to protein synthesis. Low heterogeneity is desirable from a clinical perspective, as high heterogeneity is often associated with persistence and treatment survival. Additionally, we observed a strong correlation between morphological alterations and growth inhibition across all antibiotics and species tested. This led to the development of a novel morphological parameter, MOR50, which enables rapid estimation of MIC for antibiotic susceptibility testing (AST) with a single snapshot after just 2.5 hours of incubation. In addition to introducing a novel, resource-efficient and rapid AST method, our findings shed new light on the system-level effects of antibiotic perturbations on bacteria, which might inform treatment design.

PMID:39908318 | PMC:PMC11835381 | DOI:10.1371/journal.ppat.1012924

J Gen Virol. 2025 Jan;106(1):002069. doi: 10.1099/jgv.0.002069.

ABSTRACT

Bromoviridae is a family of plant viruses with tripartite, positive-sense RNA genomes of about 8 kb in total. Genomic RNAs are packaged in separate virions that may also contain sub-genomic, defective or satellite RNAs. Virions are variable in morphology (spherical or bacilliform) and may be transmitted between hosts mechanically, via pollen, or non-persistently by insect vectors. Members of the family are responsible for major disease epidemics in fruit, vegetable and fodder crops such as tomatoes, cucurbits, bananas, fruit trees, common beans and alfalfa. Since the adoption of metagenomic high-throughput sequencing methodologies, there has been a notable increase in the number of species in the genus Ilarvirus. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Bromoviridae, which is available at ictv.global/report/bromoviridae.

PMID:39888330 | PMC:PMC11784748 | DOI:10.1099/jgv.0.002069

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

Thorax. 2025 Mar 18;80(4):255-263. doi: 10.1136/thorax-2024-222596.

ABSTRACT

Acute respiratory distress syndrome (ARDS) is present in >10% of all people admitted to critical care and is associated with severe morbidity and mortality. Despite more than half a century since its first description, no efficacious pharmacological therapies have been developed, and little progress has been made in improving clinical outcomes. Neutrophils are the principal drivers of ARDS, with their priming and subsequent aberrant downstream functions, including interleukin (IL) 1β and IL-18 secretion, central to the disease pathogenesis. The dominant pathways through which IL-1β and IL-18 are believed to be elaborated are multimeric protein structures called inflammasomes that consist of sensor proteins, adaptor proteins and an effector enzyme. The inflammasome's initial activation depends on one of a variety of damage-associated (DAMP) or pathogen-associated (PAMP) molecular patterns. However, once activated, a common downstream inflammatory pathway is initiated regardless of the specific DAMP or PAMP involved. Several inflammasomes exist in humans. The nucleotide-binding domain leucine-rich repeat (NLR) family, pyrin domain-containing 3 (NLRP3), inflammasome is the best described in the context of ARDS and is known to be activated in both infective and sterile cases. The NLR family, caspase activation and recruitment domain-containing 4 (NLRC4) and absent in melanoma 2 (AIM2) inflammasomes have also been implicated in various ARDS settings, as have inflammasome-independent pathways. Further work is required to understand human biology as much of our knowledge is extrapolated from rodent experimental models. Experimental lung injury models have demonstrated beneficial responses to inflammasome, IL-1β and IL-18 blockade. However, findings have yet to be successfully translated into humans with ARDS, likely due to an underappreciation of the central role of the neutrophil inflammasome. A thorough understanding of inflammasome pathways is vital for critical care clinicians and researchers and for the development of beneficial therapies. In this review, we describe the central role of the inflammasome in the development of ARDS and its potential for immunomodulation, highlighting key areas for future research.

PMID:39884849 | DOI:10.1136/thorax-2024-222596

Infect Prev Pract. 2024 Dec 26;7(1):100435. doi: 10.1016/j.infpip.2024.100435. eCollection 2025 Mar.

ABSTRACT

Antibiograms have been used during outbreak investigations for decades as a surrogate for genetic relatedness of Methicillin-resistant Staphylococcus aureus (MRSA). In this study, we evaluate the accuracy of antibiograms in detecting transmission, using genomic epidemiology as the reference standard. We analysed epidemiological and genomic data from 1,465 patients and 1,465 MRSA isolates collected at a single clinical microbiology laboratory in the United Kingdom over a one-year period. A total of 132 unique antibiograms (AB) were identified based on VITEK 2 susceptibility testing, with two profiles (AB1 and AB2) accounting for 698 isolates (48%). We identified MRSA-positive patients with a known hospital or community contact and evaluated the prediction of MRSA transmission based on identical antibiograms. The sensitivity and specificity of identical antibiograms to infer genetically related MRSA isolates (≤25 SNPs) within hospital contacts (presumed transmission events) was 66.4% and 85.5% respectively and 73.8% and 85.7% within community contacts. Reanalysis, where any single drug mismatch in susceptibility results was allowed, increased sensitivity but reduced specificity: 95.2% and 58.8%, respectively, for hospital contacts; and 91.7% and 62.6% for community contacts. Overall, the sensitivity and specificity of identical antibiograms for inferring genetically related MRSA isolates (≤25 SNPs), regardless of epidemiological links, were 49.1% and 87.5%, respectively. We conclude that using an antibiogram with one mismatch can detect most transmission events; however, its poor specificity may lead to an increased workload through the evaluation of numerous pseudo-outbreaks. This study further supports the integration of genomic epidemiology into routine practice for the detection and control of MRSA transmission.

PMID:39877244 | PMC:PMC11772957 | DOI:10.1016/j.infpip.2024.100435