Microbial pathogenesis最新文献

{"title":"Efficacy of bacteriophage cocktails administered through mucosal and non-mucosal routes for urinary tract infections caused by Enterobacter cloacae: A preclinical study","authors":"Srishti Singh ,&nbsp;Alok Kumar Singh ,&nbsp;Alakh Narayan Singh ,&nbsp;Sudhir Kumar Singh ,&nbsp;Virendra Bahadur Yadav ,&nbsp;Mayank Gangwar ,&nbsp;Minakshi Sahu ,&nbsp;Deepak Kumar ,&nbsp;Gopal Nath","doi":"10.1016/j.micpath.2025.108024","DOIUrl":"10.1016/j.micpath.2025.108024","url":null,"abstract":"<div><div>This preclinical study assessed the effectiveness of a phage cocktail in completely curing <em>Enterobacter cloacae</em>-associated urinary tract infections (UTIs) in a mouse model, employing various routes and dosages (both in quantity and frequency). Three lytic phages, designated ΦENT1, ΦENT2, and ΦENT3, were identified and characterised phenotypically using transmission electron microscopy (TEM) and genotypically through ERIC and restriction enzyme analysis. To induce a UTI, ten groups of female Swiss albino mice were inoculated with 100 μL containing 1 × 10⁹ CFU/mL via the urethral route with <em>E. cloacae</em> GNENT11213. The mice were subsequently treated with the phage cocktail via subcutaneous, oral, transurethral, and rectal routes. The efficacy of these routes was optimised at two doses of phages, namely 1 × 10⁹ PFU/mL (5 mice) and 1 × 10⁵ PFU/mL (5 mice). Furthermore, the levels of Endotoxins and Interleukin-6 (IL-6) were measured to assess the negative impact of phage therapy. Our findings indicated that <em>E. cloacae</em> GNENT11213 could be effectively eliminated with one dosage of 1 × 10⁹ Plaque-Forming Units per mouse (PFU/mouse) and two doses of the phage cocktail containing 1 × 10⁵ PFU/mouse administered through the urethra (local mucosa). Interestingly, higher concentrations of phage particles and multiple doses were necessary for other mucosal routes, such as oral and rectal administration, to effectively eradicate <em>E. cloacae</em> GNENT11213 at any stage of acute illness UTI. Furthermore, phage treatment did not significantly alter the levels of IL-6 and Endotoxins. Non-mucosal routes, such as subcutaneous, were ineffective in curing the infection.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"209 ","pages":"Article 108024"},"PeriodicalIF":3.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Untangling the metabolome of resistant (VBN4) and susceptible (CO5) blackgram cultivar bacterized with Bacillus pumilus imparts resistance response against yellow mosaic disease","authors":"R. Sariga ,&nbsp;B.R. Ajesh ,&nbsp;P. Renukadevi ,&nbsp;S. Nakkeeran ,&nbsp;I. Yesuraja ,&nbsp;J. Ramalingam ,&nbsp;A. Yuvaraja","doi":"10.1016/j.micpath.2025.108051","DOIUrl":"10.1016/j.micpath.2025.108051","url":null,"abstract":"<div><div>Mungbean yellow mosaic virus (MYMV), a begomovirus transmitted by the whitefly <em>Bemisia tabaci</em>, is one of the most destructive pathogens affecting blackgram (<em>Vigna mungo</em>), causing substantial yield losses across India. In the present study, MYMV inoculum was established in the susceptible cultivar CO5 via viruliferous whitefly transmission and confirmed through PCR amplification of the coat protein (CP) gene. Comparative screening of resistant (VBN4) and susceptible (CO5) cultivars validated the complete resistance of VBN4 (RC) and high susceptibility of CO5 (SC). Twenty bacterial endophytes and rhizosphere isolates were evaluated for their antiviral potential under controlled conditions. Among these, <em>Bacillus pumilus</em> SVR1 demonstrated complete suppression of MYMV symptoms with 0 % PDI as against 80 % PDI in untreated control, delayed symptom onset, and significant enhancement of plant growth in comparison with control. Untargeted GC-MS metabolite profiling revealed that SVR1-treated infected plants accumulated higher levels of defense-associated metabolites, including phenolic compounds, unsaturated fatty acids, and inositol derivatives. KEGG pathway enrichment indicated the involvement of linoleic acid metabolism, glycerolipid metabolism, and inositol phosphate metabolism in antiviral defense. Furthermore, molecular docking analysis identified soyasapogenol-B as the most potent antiviral candidate, exhibiting high binding affinity (−9.0 to −7.4 kcal/mol) against multiple MYMV proteins, including CP, Rep, MP, and TrAP, suggesting a multi-target inhibitory mechanism. This integrated approach, combining biological control, metabolomics, and <em>in silico</em> molecular docking is distinct and the first of its kind for MYMV management.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"209 ","pages":"Article 108051"},"PeriodicalIF":3.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibacterial activity of silver nanoparticles against MDR Corynebacterium pseudotuberculosis isolated from caseous lymphadenitis cases","authors":"Eman M. Elghazaly ,&nbsp;Hebatallah M. Saad ,&nbsp;Samy A. Khaliel ,&nbsp;Helmy A. Torky ,&nbsp;Dalia Fouad ,&nbsp;Athanasios Alexiou ,&nbsp;Marios Papadakis ,&nbsp;Asmaa T. Kassih ,&nbsp;Maii A. Abdelnaby ,&nbsp;Gaber El-Saber Batiha","doi":"10.1016/j.micpath.2025.108038","DOIUrl":"10.1016/j.micpath.2025.108038","url":null,"abstract":"<div><div><em>Corynebacterium pseudotuberculosis (C. pseudotuberculosis)</em> is a zoonotic pathogen with a poor treatment outcome. It causes a number of chronic disorders, such as caseous lymphadenitis (CLA) in sheep and goats. Also, it can spread to humans and cause potential health events. 120 samples from infected organs and abscessed lymph nodes of sheep and goats with caseous lymphadenitis pyogranulomas were isolated. 10 % (12) of samples were positive for C. <em>pseudotuberculosis by</em> phenotypic methods, pathogenicity testing of guinea pigs, and PCR for the 16 S rRNA. Then they were characterized for their antibiotic susceptibility. We studied the effect of silver nanoparticles (Ag-NPs) on a pan-drug-resistant strain of <em>C. pseudotuberculosis</em> that showed resistance to six classes of antibiotics. In this study, the minimum inhibitory concentration (MIC) was 0.1 mg/ml (100 ppm) and the minimum bactericidal concentration (MBC) of Ag-NPs were 0.05 mg/ml (50 ppm). In this study, the effects of <em>Ag-NPs on the C. pseudotuberculosis morphology,</em> indicated by scanning electron microscopy (SEM) at Matrouh Governorate, revealed pronounced morphological changes indicating damage and rupture of the bacterial membrane. In conclusion, Ag-NPs could be a promising treatment for <em>caseous lymphadenitis</em> pyogranuloma<em>s</em>.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"209 ","pages":"Article 108038"},"PeriodicalIF":3.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From phylogeny to photonics: A smart spectroscopic approach assisted with neural networks for rapid typing of Enterobacteriaceae isolates from chicken meat","authors":"Dina S. Arabi ,&nbsp;Omnia Hamdy ,&nbsp;Zienab A. Abdel-Salam ,&nbsp;Mahmoud S.M. Mohamed ,&nbsp;Mohamed Abdel-Harith","doi":"10.1016/j.micpath.2025.108040","DOIUrl":"10.1016/j.micpath.2025.108040","url":null,"abstract":"<div><div>Bacteria are ubiquitous organisms; while many are harmless, some can cause serious disease outbreaks. Nearly a quarter of the global food supply is ruined by microbial activity, such as spoilage microorganisms or disease-causing pathogens, leading to substantial economic losses and human safety problems. Most mishaps associated with bacterial contamination could be avoided if a 100 % accurate, easy-to-use, rapid detector/identifier of bacteria was available. Compared to the time-consuming and complicated conventional molecular characterization methods, laser-induced breakdown spectroscopy (LIBS) combined with appropriate chemometric analysis provides a potential approach for the rapid and reliable characterization of bacterial species. This study identified isolated bacterial contaminants from store-bought chicken fillets using molecular characterization of the polymerase chain reaction (PCR) products of small subunit 16S rRNA sequences. Eight different strains were identified, all belonging to the family <em>Enterobacteriaceae</em>. Phylogenetic relationships were investigated using a constructed phylogenetic tree. In this study, nanoparticle-enhanced laser-induced breakdown spectroscopy (NELIBS) was used to differentiate bacterial samples based on their elemental composition. Spectral data were analyzed using principal component analysis (PCA) to explore the variance between the pure bacterial samples. With a cumulative variance between 95 % and 97 %, sample groups at closely related taxonomic levels (genus, species, and subspecies) could be discriminated. The robustness of the LIBS characterization was tested in the presence of a second bacterial species in the ablated specimen using mixtures of bacterial cultures at different concentrations. Using artificial neural networks (ANN), the spectral data were classified with an accuracy of up to 100 %.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"209 ","pages":"Article 108040"},"PeriodicalIF":3.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthetic antimicrobial peptides: Combatting antimicrobial resistance for sustainable aquaculture","authors":"Yamini Lohumi ,&nbsp;Raja Aadil Hussain Bhat ,&nbsp;Amit Pande","doi":"10.1016/j.micpath.2025.108029","DOIUrl":"10.1016/j.micpath.2025.108029","url":null,"abstract":"<div><div>The widespread use of antibiotics has resulted in the development of antibiotic-resistant bacteria, raising major public health concerns. This highlights the urgent need for alternative molecules that are safe for the environment. In this context, researchers are exploring antimicrobial peptides (AMPs) as viable alternative antibiotics for treating these diseases. Despite their potential, natural AMPs have several limitations, including limited efficacy in biological systems, high production costs, toxicity to host cells, and low <em>in vivo</em> stability. To address these challenges, researchers are focusing on designing synthetic AMPs with enhanced stability, efficacy, and targeted antimicrobial action. This review provides a comprehensive overview of the necessity for designing synthetic AMPs in aquaculture and their environmental implications. We discuss the issue of antibiotic resistance and various strategies for designing highly potent and improved synthetic analogs of natural AMPs. Additionally, the review covers various computational tools and machine learning-based approaches that facilitate AMP prediction and rational design, enabling the development of peptides with improved therapeutic properties. By integrating advances in synthetic biology and computational modelling, synthetic AMPs offer a promising, sustainable solution for disease control in aquaculture, reducing reliance on conventional antibiotics and enhancing aquatic animal health.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"209 ","pages":"Article 108029"},"PeriodicalIF":3.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitory effect of an ethnoveterinary oil and water formulation on LTA-induced mastitis via TLR2/NF-κB signaling in mammary epithelial cells","authors":"Ratheesh M ,&nbsp;Svenia P. Jose ,&nbsp;S. Sheethal ,&nbsp;Sony Rajan ,&nbsp;S. Sandya","doi":"10.1016/j.micpath.2025.108041","DOIUrl":"10.1016/j.micpath.2025.108041","url":null,"abstract":"<div><div>Mastitis, an inflammatory disease, becoming a problematic condition in the dairy industry, which causes severe economic loss. It is primarily infected by <em>Staphylococcus aureus</em> (<em>S. aureus</em>). Current conventional therapies for mastitis often lead to antibiotics resistance. To address this issue, a plant based ethnoveterinary medicine approach is being explored as a potential treatment for this condition. The aim of the present study was to evaluate the anti-inflammatory and anti-mastitis effect of oil based (EO) and water based (EW) ethno veterinary formulations in Lipoteichoic acid (LTA) stimulated HC11 cells. LTA induced inflammatory model in HC11 mouse mammary epithelial cells were used in this study. The inflammatory genes expressions such as inducible nitric oxide synthase (iNOS), Toll like receptor 2 (TLR2), and NF-κB p65 were analysed by RT-PCR analysis. The antioxidant enzymes and inflammatory mediators were analysed using ELISA method. NAGase activity was analysed by using colorimetric method. Reactive oxygen species (ROS) generation was assessed by fluorescent microscopy method. Results revealed that EO inhibited the production of nitric oxide (NO), Lipid perioxidation and the gene expression of iNOS, TLR2, and NF-κB p65 in the LTA-induced HC11 cells. Moreover, the DCFH-DA staining showed that EO enhances the endogenous antioxidant enzymes activity and mitigated the oxidative stress and ROS generation. Also, results showed that the treatment with EO possesses potent anti-mastitis effect by inhibiting NAGase activity. These results indicated that EO exhibits its anti-inflammatory and anti-mastitis effects mainly through attenuating TLR2 and NF-κB signaling pathway. Hence, EO could be a potential therapeutic agent against mastitis.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"209 ","pages":"Article 108041"},"PeriodicalIF":3.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing host-adaptation of new sequence types of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA)","authors":"Ricardo Oliveira ,&nbsp;Daniela Araújo ,&nbsp;Joana Castro ,&nbsp;Teresa Nogueira ,&nbsp;Gonçalo Almeida ,&nbsp;Nuno F. Azevedo ,&nbsp;Carina Almeida","doi":"10.1016/j.micpath.2025.108042","DOIUrl":"10.1016/j.micpath.2025.108042","url":null,"abstract":"<div><div>The importance of animals as reservoirs of human pathogens is widely recognised, with livestock-associated methicillin-resistant <em>Staphylococcus aureus</em> (LA-MRSA) being consistently reported. This study presents a phenotypic and genotypic characterization of five MRSA isolates from raw bovine milk in northern Portugal, using culturomics and whole genome sequencing (WGS), to assess their potential risk for human infection. Resistance to beta-lactams was confirmed by the presence of the <em>mecA</em> resistance gene as part of the SCC<em>mec</em> type V element (5C2&amp;5), complemented by a resistance profile to other antibiotics characteristic of adaptation to animal hosts. Several virulence factors were identified, including some with potential human tropism, such clumping factors, gamma-hemolysins and staphylococcal complement inhibitors. All MRSA isolates gave rise to new sequence types (ST), newly added to the MLST database as ST8475, ST8894 and ST8895, which show a variation of 1 or 2 alleles compared to the recognised LA-MRSA ST398/CC398 lineage. A phylogenetic comparison of these MRSA isolates with other <em>S. aureus</em> isolates confirmed a close genetic relationship with the ST398/CC398 lineage. This finding further supports the inclusion of these new STs in this clonal complex. A pathogenicity <em>in vivo</em> test using the <em>Galleria mellonella</em> model, which has an innate immune system similar to humans, showed a high pathogenicity of the MRSA isolates, and an assessment of biofilm production showed a similar capacity for biomass formation among all isolates. These findings demonstrate a typical adaptation of the isolates to animal hosts, while retaining or acquiring traits associated with the ancestral human host of <em>S. aureus.</em> Such dual adaptation emphasizes their zoonotic potential and strengthens the relevance of LA-MRSA as a critical public health concern.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"209 ","pages":"Article 108042"},"PeriodicalIF":3.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of apoptosis, oxidative stress and specific cardiovascular biomarkers to demonstrate myocardial damage in neonatal calves infected with different infectious agents","authors":"Murat Uzti̇mür ,&nbsp;Muhammed Bahaeeddin Dörtbudak ,&nbsp;Cennet Nur Ünal ,&nbsp;Meltem Sağiroğlu","doi":"10.1016/j.micpath.2025.108037","DOIUrl":"10.1016/j.micpath.2025.108037","url":null,"abstract":"<div><div>In human medicine, there is evidence to suggest that myocarditis may be present in cases of diarrhea associated with various infectious agents. Nevertheless, the question of whether etiological agents cause myocardial damage in calves with diarrhea remains unanswered in the field of veterinary medicine. Based on this, we aimed to determine the presence of myocardial damage, cellular oxidative damage and apoptosis in calves with sepsis using high-sensitivity biomarkers. The study material consisted of 55 acute diarrheal calves and ten healthy controls. The diarrheic calf group consisted of <em>rotavirus</em> (n = 10), <em>coronavirus</em> (n = 10), <em>cryptosporidium parvum</em> (<em>C. parvum</em>) (n = 10), <em>giardia lamblia</em> (n = 10), and non-survivors (n = 15). Cardiac histopathology and immunohistochemical (Heat shock proteins 27 and caspase 3) analyses were performed on 15 calves that did not survive the study. In sepsis calves, high sensitivity cardiac troponin-I, fatty acid binding protein 3, creatine kinase myocardial band, L-lactate, and anion gap concentrations were significantly higher than in the control group. In the histopathological examination of the heart of the calves that did not survive, degenerative-necrotic, cellular damage, inflammatory cell infiltration, and vascular changes were observed, while immunohistochemical examination determined that oxidative damage and intense apoptosis occurred.</div><div>In conclusion, the presence of myocardial damage in sepsis calves was confirmed by both histopathological and immunohistochemical techniques and serum cardiac specific biomarker concentration analyses. It was also shown that anion gap, bicarbonate, and L-lactate also contribute to the formation of myocardial damage.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"208 ","pages":"Article 108037"},"PeriodicalIF":3.5,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145060012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacteriophage as a promising approach for the biocontrol of typical pathogenic bacteria Escherichia coli in fecal environment","authors":"Haipeng Li ,&nbsp;Shuoxin Yang ,&nbsp;Christopher W.K. Chow ,&nbsp;Fang Liu ,&nbsp;Xiangqun Zheng","doi":"10.1016/j.micpath.2025.108032","DOIUrl":"10.1016/j.micpath.2025.108032","url":null,"abstract":"<div><div>Toilet feces are a major source of environmental pollution and public health issues, harboring a wide range of pathogens. Bacteriophage therapy, a promising biological control method for eliminating pathogenic bacteria, offers advantages such as high specificity, safety, and rapid proliferation. In this study, the bacteriophage LYE-01, isolated from feces using <em>Escherichia coli</em> (<em>E</em>. <em>coli)</em> as the target pathogen, demonstrated strong environmental tolerance. It survived within a pH range of 4–11, at temperatures of 10–50 °C, and following ultraviolet irradiation for up to 20 min. Comprehensive genomic analysis of LYE-01 revealed an absence of virulence and antibiotic resistance genes, confirming its safety for both environmental and human health. In the experiments of evaluating the bacteriophage's efficacy in removing pathogenic bacteria, LYE-01 exhibited an inhibitory effect on its host bacteria across different multiplicity of infection (MOI) conditions. The highest inactivation efficiency of LYE-01 on <em>E</em>. <em>coli</em> was 64.5 % at the optimal MOI = 1, providing a crucial experimental basis for the subsequent application of this bacteriophage. This newly isolated bacteriophage represents a promising tool for reducing fecal sewage contamination, mitigating environmental pollution, and improving rural environmental health.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"209 ","pages":"Article 108032"},"PeriodicalIF":3.5,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of CRISPR-Cas9 mediated knockout of IRF3 gene in BHK-21 cells on immune gene expression and foot-and-mouth disease virus replication","authors":"Lekshmi J. Das,&nbsp;Gnanavel Venkatesan,&nbsp;Narayanan Krishnaswamy,&nbsp;Indu Shekhawat,&nbsp;Umapathi Vijayapillai,&nbsp;M. Priyanka,&nbsp;H.J. Dechamma","doi":"10.1016/j.micpath.2025.108022","DOIUrl":"10.1016/j.micpath.2025.108022","url":null,"abstract":"<div><div>Foot-and-mouth disease (FMD) is an acute highly contagious viral disease of cloven-hoofed animals. Currently, FMD vaccine production and research mainly depend on the BHK-21 cell line. BHK-21 is highly sensitive to FMD virus, however, still a lot of room for improvement that can result in higher antigen yield in vaccine production facilities. IRF3 (Interferon regulatory factor 3) is a key transcription regulatory factor involved in the interferon (IFN) pathway, the immediate antiviral response of the cells. In this study, IRF3 knock-out (KO) BHK-21 cells were established using the CRISPR-Cas9 method. The KO cell line was stable in growth and morphological characteristics, unveiled in growth curve analysis. After infection with FMDV, the viral copy number, virus titer, and plaque forming units (PFU) were significantly increased in KO cells than those in parental BHK-21 (NC) cells. The relative gene expression of type I IFNs and ISGs such as IRF3, IRF7, viperin, Mx1 and ISG15 upon FMDV infection was severely reduced in KO cells. Results preliminarily reveal the role of IRF3 in cellular antiviral immune response, and the IRF3-KO cell line could also serve as a useful tool for FMDV research and vaccine production.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"208 ","pages":"Article 108022"},"PeriodicalIF":3.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145060011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}