Microbial pathogenesisPub Date : 2025-11-01Epub Date: 2025-08-06DOI: 10.1016/j.micpath.2025.107966
Farha Naz, Mohd Arish, Sugandha Singh, Nilofer Naqvi, Anwar Alam
{"title":"Mycobacterium tuberculosis PE5 stimulates anti-inflammatory cytokine production via innate immune toll-like receptor 4 signaling.","authors":"Farha Naz, Mohd Arish, Sugandha Singh, Nilofer Naqvi, Anwar Alam","doi":"10.1016/j.micpath.2025.107966","DOIUrl":"10.1016/j.micpath.2025.107966","url":null,"abstract":"<p><p>Mycobacterium tuberculosis possesses an intricate system of virulence factors that aid in providing resilience to the pathogen within the milieu of the host. M.tb expresses unique proteins, PE/PPE, that are conserved and play a crucial role in pathogenesis. A conserved member of the PE family Rv0285 (PE5) of Mycobacterium tuberculosis (M.tb) has been earlier characterized as an essential and secretory protein that is a critical regulator of host immune response. We have shown that the PE5 protein consists of lysosomal targeting sequences and is stable at low pH, thereby allowing the protein to be localized to the lysosome. In-silico studies suggest that PE5 interacts with TLR4. This was validated using the TLRs knockout macrophage cell lines. PE5 increases the anti-inflammatory cytokine via the TLR4 receptor. Recombinant M. smegmatis expressing M.tb-PE5 protein survives within the macrophage as compared to control M. smegmatis, suggesting its role in providing resilience to survive within the macrophage. FDA drugs were screened for that interaction with the PE5 protein. Interaction of Nystatin and Conivaptan hydrochloride with PE5 results in stable binding and provides proof of concept about the possibility of repurposing these molecules as an anti-tubercular drug.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"107966"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799543","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}
Microbial pathogenesisPub Date : 2025-11-01Epub Date: 2025-08-05DOI: 10.1016/j.micpath.2025.107964
Olga Loginova, Violetta Vlasova, Nadezhda Shmagel, Evgeniya Saidakova
{"title":"A shift towards Th2 and changes in the distribution into T<sub>naϊve</sub>, T<sub>CM</sub>, T<sub>EM</sub>, and T<sub>EM</sub>RA subsets in HIV-infected non-responders.","authors":"Olga Loginova, Violetta Vlasova, Nadezhda Shmagel, Evgeniya Saidakova","doi":"10.1016/j.micpath.2025.107964","DOIUrl":"10.1016/j.micpath.2025.107964","url":null,"abstract":"<p><p>The decrease in CD4<sup>+</sup> T-cell count, as well as a shift of Th1/Th2 towards Th2, are typical for HIV-infected people before treatment and associated with increased mortality risks. Studies of Th2 frequencies in HIV-infected patients receiving highly-active antiretroviral therapy (ART) have shown conflicting results and did not take into account CD4<sup>+</sup> T-cell counts. We qualified the frequencies of Th1 (CD4<sup>+</sup>T-bet<sup>+</sup>IFNγ<sup>+</sup>) and Th2 (CD4<sup>+</sup>GATA-3<sup>+</sup>IL-4<sup>+</sup>) in HIV-infected individuals on ART using flow cytometry, considering the efficiency of CD4<sup>+</sup> T-cell recovery. Additionally, we assessed the expression of CCR7 and CD45RO to determine the effector potential of the studied cells. We found that immunological non-responders (INRs), with CD4<sup>+</sup> T-cell count <350 cells/μL, have increased frequencies of Th2 (Median (Me) = 3.35 %) compared to complete responders (CRs), with CD4<sup>+</sup> T-cell count >500 cells/μL (Me = 2.52 %, p = 0.035) and HIV-negative individuals (Me = 2.19 %, p = 0.007). This, along with a decrease in the number of Th2 in INRs (Me = 6.9 cells/μL), compared to CRs (Me = 14.0 cells/μL, p = 0.027) and HIV-negative individuals (Me = 15.8 cells/μL, p = 0.009), indicates differential regulatory processes that ensure the Th2 survival not only in the early stages of HIV infection, but also during long-term ART. Furthermore, the distribution of peripheral blood CD4<sup>+</sup>, Th1 and Th2 cells into T<sub>naϊve</sub>/T<sub>CM</sub>/T<sub>EM</sub>/T<sub>EM</sub>RA subsets varied significantly: approximately half of CD4<sup>+</sup> T-cell are naive, the majority of Th1 are T<sub>EM</sub> and the most numerous population of Th2 is T<sub>CM</sub>. INRs demonstrated a decrease in naive CD4<sup>+</sup> T-cells (Me = 38.9 %, p = 0.041), compared to CRs Me = 57.7 %) and reduction of naive Th2 cells (Me = 11.4 %, p = 0.049), compared to CRs Me = 16.9 %). In addition, we note some minor expansion of T<sub>EM</sub> cells among Th1 and Th2 in INRs. Correlation analysis demonstrated a positive relationship between Th1 and Th1 T<sub>EM</sub> (r = 0.85, p = 0.003) frequencies, as well as negative correlations between Th2 and Th2 T<sub>CM</sub> (r = -0.71, p = 0.027), Th1 and Th1 naive (r = -0.92, p = 0.0004) and CD4<sup>+</sup> and CD4<sup>+</sup>T<sub>EM</sub> (r = -0.66, p = 0.044) frequencies in INRs. Evidently, the CD4<sup>+</sup> T-cell deficiency in INRs is associated with subset-specific alterations, which may include shifts in the cell frequencies and effector potential.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"107964"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794831","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":"Chrysin inhibits PEDV replication by antagonizing apoptosis via the ROS/JNK/p53 axis.","authors":"Yupeng Zhi, Yupeng Ren, Xuemei Xia, Qiao Tian, Yingshi Meng, Siyu Tao","doi":"10.1016/j.micpath.2025.107957","DOIUrl":"10.1016/j.micpath.2025.107957","url":null,"abstract":"<p><p>Porcine epidemic diarrhea virus (PEDV) remains a significant threat to global swine industry, with immunization strategies limited by viral genome variation and a lack of effective therapeutic drugs. The flavonoid compound chrysin has shown potential anti-PEDV activity, but its specific antiviral mechanisms remain unclear. This study validated the inhibitory effect of chrysin on PEDV using IFA and qPCR. Additionally, Transcriptome sequencing was conducted on PEDV-infected Vero cells with and without chrysin treatment to reveal its antiviral mechanism. The results showed that 5813 DEGs at 12 hpi and 3374 DEGs at 24 hpi, with enrichment in pathways related to transcription, translation, metabolism, innate immunity, and apoptosis. Notably, KEGG analysis indicated that Chrysin regulate PEDV-induced apoptosis by modulating the TNF, MAPK, and p53 signaling pathways, which might antagonize PEDV infection. Subsequent results confirmed that chrysin can significantly downregulate the reactive ROS levels and cell apoptosis rate induced by PEDV infection (P<0.05), and inhibit the activation of the JNK and p53 pathways, including the phosphorylation of ASK1, JNK, and p53. Chrysin also significantly reduced cleaved caspase 3/8/9 levels and Bax/Bcl-2 ratios, thereby affecting PEDV N protein expression (P < 0.05). Moreover, similar inhibitory effects on PEDV can also be achieved through the JNK inhibitor SP600125 and the p53 inhibitor PFT-α. These findings revealed that chrysin can antagonize PEDV-induced apoptosis through the ROS/JNK/p53 signaling axis, thereby inhibiting viral replication. This study provides a scientific basis for developing chrysin as a novel anti-PEDV drug and offers insights into the screening and research of antiviral drug targets.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"107957"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794833","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}
Microbial pathogenesisPub Date : 2025-11-01Epub Date: 2025-08-05DOI: 10.1016/j.micpath.2025.107959
Jingyu Wang, Zhen Wang, Shaobing Wan, Shaotang Ye, Qi Li, Yongbo Liu, Xing Liu, Zihan Chen, Shizhe Liu, Qingmei Xie, Heng Wang, Kun Jia, Shoujun Li
{"title":"Lumpy skin disease virus ORF142 suppresses the cGAS/STING-mediated IFN-I pathway through NBR1-mediated STING autophagic degradation.","authors":"Jingyu Wang, Zhen Wang, Shaobing Wan, Shaotang Ye, Qi Li, Yongbo Liu, Xing Liu, Zihan Chen, Shizhe Liu, Qingmei Xie, Heng Wang, Kun Jia, Shoujun Li","doi":"10.1016/j.micpath.2025.107959","DOIUrl":"10.1016/j.micpath.2025.107959","url":null,"abstract":"<p><p>Lumpy skin disease (LSD), caused by the Lumpy skin disease virus (LSDV), poses a significant threat to the global cattle farming industry. Viral proteins evolved the ability to escape host immune responses. Here, we demonstrate that LSDV infection inhibits interferon-β (IFN-β) production in Madin-Darby bovine kidney (MDBK) cells, even in the presence of Sendai virus (SEV) inducers. Through further investigation, we identify multiple genes at both ends of the LSDV genome that strongly inhibit IFN-β or NF-κB activation of the promoter. Notably, ORF142 selectively inhibits IFN-β promoter activity but fails to inhibit NF-κB promoter activity. Subsequently, we reveal that ORF142 negatively regulate the cGAS/STING-mediated IFN-I production. Overexpression of ORF142 suppresses IFN-β and interferon-stimulated response element (ISRE) activity, while the absence of ORF142 upregulates the transcription levels of IFN-β and interferon-stimulated genes (ISGs) in MDBK cells. Mechanistically, ORF142 interacts with STING to facilitate autophagy-lysosomal degradation by recruiting NBR1, thereby impeding the activation of downstream signaling molecules, such as IRF3, and inhibiting IFN-I production. In conclusion, our findings elucidate the immune evasion mechanism of ORF142 encoded by LSDV, offering insights for the development of antiviral drugs or attenuated live vaccines to mitigate LSD.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"107959"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799542","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}
Microbial pathogenesisPub Date : 2025-11-01Epub Date: 2025-08-06DOI: 10.1016/j.micpath.2025.107965
Yoshiyasu Takefuji
{"title":"Platinum nanoparticles with photocatalytic binders for swift virus inactivation on textiles and surfaces.","authors":"Yoshiyasu Takefuji","doi":"10.1016/j.micpath.2025.107965","DOIUrl":"10.1016/j.micpath.2025.107965","url":null,"abstract":"<p><p>Platinum nanoparticles combined with photocatalytic binders enable rapid virus inactivation on diverse surfaces, achieving 99.97 % reduction of Influenza A and 99.9 % of Feline Calicivirus in 15 s. This eco-efficient approach ensures uniform nanoparticle distribution, minimizing waste and offering sustainable antiviral protection for healthcare and other settings, dramatically outperforming existing solutions that require up to 5 min. We tested against Influenza A and Feline Calicivirus, with potential implications for norovirus due to similar viral structures, pending further validation. The binders' role in ensuring uniform nanoparticle distribution represents a breakthrough in sustainable protection technologies, enabling rapid virus inactivation while minimizing material usage across diverse materials including plastics, metals, ceramics, glass, and composites. In healthcare settings such as ICUs, this green technology significantly reduces waste generation and environmental impact while maintaining optimal protection against both current and emerging viral threats.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"107965"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804431","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":"Isolation, characterization, therapeutic potential and depolymerase identification of a lytic bacteriophage Kpp-9 against Klebsiella pneumoniae with capsule serotype K2.","authors":"Menglu Wang, Jiayi Liu, Xin Jiao, Yanxia Liu, Shuqi Yang, Wenbin Gong, Jinjuan Qiao","doi":"10.1016/j.micpath.2025.107950","DOIUrl":"10.1016/j.micpath.2025.107950","url":null,"abstract":"<p><p>Klebsiella pneumoniae is one of the most threatening multidrug-resistant bacteria, and its inherent capsule and extensive biofilm formation pose a significant barrier to the treatment of infection. Bacteriophages (or phages) and phage-derived depolymerases are attracting attention as potential alternatives to antibiotics. Here, we isolated a lytic phage, named Kpp-9, using a capsule-type K2 strain, Kp09. Kpp-9 could inhibit bacterial biofilm formation, eradicate the mature biofilm in vitro, improve the survival rate of Kp09-infected mice, and alleviate the symptoms of pneumonia in mice. Morphological and genomic analyses showed that phage Kpp-9 belonged to the class Caudoviricetes and no virulence or resistance genes were found in the genome, indicating potential therapeutic applications of phage Kpp-9. Furthermore, two depolymerases (Kp9042 and Kp9050) were predicted and shown to be able to digest the capsule and improve the susceptibility of K. pneumoniae to complement-mediated serum killing. In addition, Kpp-9 and two depolymerases showed high selectivity for capsule-type K2 K. pneumoniae strains and exhibited robust thermal and pH stability. These results demonstrate that phage Kpp-9 and its encoded depolymerases Kp9042 and Kp9050 may serve as alternative therapeutic agents for the treatment of capsule-type K2 K. pneumoniae infections.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"107950"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799541","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":"The Gut-Lung Axis in Tuberculosis: A New Frontier in Immunomodulation and Microbiota-Directed Therapeutic Strategies.","authors":"Divya Nasare, Shashikant Bagade","doi":"10.1016/j.micpath.2025.108087","DOIUrl":"https://doi.org/10.1016/j.micpath.2025.108087","url":null,"abstract":"<p><p>Tuberculosis (TB) is a transmissible disease that contributes to the global health burden due to drug resistance. The gut-lung axis is an emerging and promising frontier for understanding Mycobacterium tuberculosis (MTB) pathogenesis and disease progression via gut and lung bidirectional communication. Increasing evidence highlights that regulation in gut and lung microbial communities, termed dysbiosis, influences homeostatic conditions, innate and adaptive responses, and susceptibility to TB. Growing research has witnessed a paradigm shift toward the immunological interplay between gut microbiota and lung microbiota, and modulation in TB. This review deals with the interplay of immune cells and gut microbiota in TB, highlighting the importance of innate and adaptive responses in stabilizing the dysbiosis and inflammation. Host-directed therapies such as probiotics, prebiotics, synbiotics, short-chain fatty acids (SCFAs), and fecal microbiota transplantation support the stabilization of gut microbiota and maintain the disease severity. Moreover, personalized microbiota therapies, such as bacteriophage therapy, diagnostic agents, and biomarkers, are explored for their several roles in maintaining the eubiosis condition. We also highlight the future perspective of addressing the knowledge gap to develop a personalized and combined approach to novel drug delivery systems and host-directed therapies. This review provides an in-depth outline of the gut-lung axis as a potential therapeutic intervention, offering a conceptual framework for developing next-generation, microbiota-directed therapies to suppress and combat MTB infection.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"108087"},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225627","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}
Dan Zhu , Haining Li , Chu Zhang , Ying Zhou , Jin Yang , Changzhou Feng
{"title":"Association of infection with Toxoplasma gondii and arthritis: Insights from a cross-sectional study and genetic epidemiology analysis","authors":"Dan Zhu , Haining Li , Chu Zhang , Ying Zhou , Jin Yang , Changzhou Feng","doi":"10.1016/j.micpath.2025.108086","DOIUrl":"10.1016/j.micpath.2025.108086","url":null,"abstract":"<div><h3>Background</h3><div><em>Toxoplasma gondii</em> (<em>T. gondii</em>), a ubiquitous protozoan infecting one-third of humanity, exhibits complex immunomodulatory properties. While experimental models suggest paradoxical roles in inflammation regulation, epidemiological data linking <em>T. gondii</em> to arthritis remain inconclusive, and the genetic causality unexplored. This multidisciplinary study integrates population epidemiology with genetic epidemiology to elucidate this relationship.</div></div><div><h3>Methods</h3><div>Analyzing 17,029 U S. adults from NHANES, we performed multivariable-adjusted logistic regression with complex survey weighting. Genetic correlations were assessed via linkage disequilibrium score regression (LDSC), complemented by bidirectional two-sample Mendelian randomization (MR) using GWAS data for three <em>T. gondii</em> serological markers (IgG, p22, sag1) and arthritis phenotypes.</div></div><div><h3>Results</h3><div><em>T. gondii</em> IgG seropositivity showed significant association with arthritis prevalence after multivariable adjustment (OR = 1.19, 95 % CI:1.03–1.38). Racial disparities were prominent, particularly in non-Hispanic whites across overall arthritis, rheumatoid arthritis (RA), and osteoarthritis (OA) (all <em>P</em><sub>interaction</sub><0.05). LDSC and forward MR revealed no genetic correlation or causal effect of <em>T. gondii</em> infection on arthritis phenotypes risk (all <em>P</em> > 0.05). Reverse MR demonstrated reduced <em>T. gondii</em> sag1 IgG levels in RA (OR = 0.92, 95 % CI:0.87–0.98) and OA (OR = 0.63, 95 % CI:0.44–0.88), suggesting impaired anti-parasitic humoral immunity.</div></div><div><h3>Conclusion</h3><div>Our study reveals a complex duality: while chronic <em>T. gondii</em> exposure correlates with arthritis susceptibility in specific populations, the genetic evidence proposes a paradigm-shifting mechanism - autoimmune dysregulation in arthritis may compromise anti-parasitic antibody responses. This bidirectional relationship advances our understanding of infection-autoimmunity crosstalk, with critical implications for managing parasitic co-infections in rheumatological care.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"209 ","pages":"Article 108086"},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221799","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}
Microbial pathogenesisPub Date : 2025-10-01Epub Date: 2025-07-21DOI: 10.1016/j.micpath.2025.107917
Aswathi Bharathan, Yaser Arafath, Aifa Fathima, Saqib Hassan, Prabhakar Singh, George Seghal Kiran, Joseph Selvin
{"title":"Corrigendum to \"Implication of environmental factors on the pathogenicity of Vibrio vulnificus: Insights into gene activation and disease outbreak\" [Microbial Pathogenesis 204 (2025) 107591].","authors":"Aswathi Bharathan, Yaser Arafath, Aifa Fathima, Saqib Hassan, Prabhakar Singh, George Seghal Kiran, Joseph Selvin","doi":"10.1016/j.micpath.2025.107917","DOIUrl":"10.1016/j.micpath.2025.107917","url":null,"abstract":"","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"107917"},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690925","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}