Microbial pathogenesis最新文献

{"title":"Microbiome analysis reveals the adverse effects of diarrhea on the gut microbiota of yaks","authors":"Dongjing Wang,&nbsp;Jiangyong Zeng","doi":"10.1016/j.micpath.2025.108218","DOIUrl":"10.1016/j.micpath.2025.108218","url":null,"abstract":"<div><div>Diarrhea exhibits a extremely high prevalence among yak calves, significantly affecting the development of the yak industry and resulting in substantial economic losses. Gut microbiota has been demonstrated to be closely related to various diseases, particularly gastrointestinal disorders. However, to date, no studies have specifically explored the relationship between diarrhea in yak calves and gut microbiota. Therefore, this study aims to characterize the alterations of gut microbiota in yak calves during diarrhea. Results indicated that the diversity and abundance of the gut bacterial community in diarrheic yak calves were significantly reduced. In contrast, the gut fungal community remains relatively stable during diarrhea, with no significant changes observed in its diversity and abundance. Although diarrhea does not affect the composition of the dominant phyla of intestinal bacteria and fungi, the abundance of some microbial taxa has experienced significant changes. Specifically, diarrhea resulted in a marked increase in 2 phyla and 14 genera, while a significant decrease was observed in 5 phyla and 137 genera in gut bacterial community. Additionally, 30 genera in the gut fungal community exhibited significant increases, whereas 12 genera demonstrated significant decreases during diarrhea. Notably, we also identified significant alterations in intestinal function during diarrhea, including cytoskeleton and carbohydrate transport, etc. Taken together, this research indicated that diarrhea significantly affects the gut microbiota in yak calves, with more pronounced changes observed in the gut bacterial community. Furthermore, this research also represents a crucial exploration of the composition and alterations of gut microbiota in diarrheic yak calves, which will help prevent and control diarrhea in yaks inhabiting high-altitude regions and promote the development of the yak industry.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"211 ","pages":"Article 108218"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145708653","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":"Gut microbiota's role in NAFLD- and HBV/HCV-related hepatocellular carcinoma: Mechanisms and therapeutic implications","authors":"Gursimran Singh ,&nbsp;Shazia Ansari ,&nbsp;Satyam Yadav ,&nbsp;Khadga Raj Aran","doi":"10.1016/j.micpath.2025.108273","DOIUrl":"10.1016/j.micpath.2025.108273","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality globally and has been closely linked to chronic liver conditions, such as viral hepatitis and non-alcoholic fatty liver disease. Recent research has demonstrated that the gut microbiota significantly impacts the gut-liver axis, a crucial aspect of the pathophysiology of HCC. This review emphasizes the mechanisms by which gut dysbiosis contributes to liver inflammation, fibrosis, and tumor formation. In NAFLD-related HCC, modification in the microbiota composition facilitates intestinal barrier dysfunction, endotoxemia, and metabolic disturbances. In HCC associated with HBV/HCV, the microbiome modulates immune surveillance and viral persistence. Shared pathogenic pathways, such as LPS-TLR4 signaling, bile acid dysregulation, and immunosuppressive microenvironments, highlight the role of microbial imbalance across varied etiologies. We also discuss how antibiotics, diet, probiotics, and postbiotics influence gut-liver homeostasis, as well as their therapeutic potential in primary and secondary prevention and treatment of HCC. Short-chain fatty acids and valeric acid are examples of postbiotics with anti-inflammatory and pro-apoptotic anti-IBD effects, while fecal microbiota transplantation and dietary modulation have shown potential in improving outcomes. The review also identifies significant research gaps, particularly in establishing causality, understanding intrahepatic metastasis, and investigating the roles of the fungal and viral microbiome (mycobiome and virome). Finally, the incorporation of microbiome-based interventions into clinical practice could represent an effective future strategy for risk stratification, prevention, and adjuvant therapy of HCC. Future studies focusing on longitudinal analysis, mechanistic validation, and multi-kingdom profiling are essential for translating microbiome research into effective clinical applications.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"211 ","pages":"Article 108273"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878634","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":"Clinicopathological and molecular characterization of Morbillivirus caprinae Lineage IV in PPR outbreak among small ruminants of Punjab","authors":"Ashok Kumar ,&nbsp;Abhishek Verma ,&nbsp;V. Mahajan ,&nbsp;Harbir Singh ,&nbsp;G. Filia ,&nbsp;Rajsukhbir Singh ,&nbsp;Jagmeet Kaur ,&nbsp;M.S. Bal","doi":"10.1016/j.micpath.2025.108246","DOIUrl":"10.1016/j.micpath.2025.108246","url":null,"abstract":"<div><div>Peste des petits ruminants (PPR) is a highly contagious viral disease affecting sheep and goats, posing a significant threat to small ruminant health and rural livelihoods in Punjab, India. <strong>The objective of the present study was to investigate cases of per-acute mortality caused by <em>Morbillivirus caprinae</em>, which resulted in the death of 24.86 % (134/539) of animals across ten different sheep and goat farms.</strong> The overall morbidity, mortality and case fatality rate were observed during the outbreak investigation. However, necropsy and histopathological findings were strongly indicative of <em>Morbillivirus caprinae</em> infection in domestic small ruminants. The presence of PPRV was confirmed through Sandwich ELISA and one-step RT-PCR assays. The study also investigated potential interspecies transmission between goats and sheep in mixed flocks during a recent PPR outbreak. Genetic analysis of samples from affected flocks in neighboring regions revealed close similarity with other Asian PPRV isolates, indicating possible regional viral circulation.</div><div>Phylogenetic analysis based on the nucleocapsid (N) protein gene revealed that the virus belonged to Lineage IV and was detected in samples from infected sheep, domestic goats, and animals from mixed farms. These findings suggest the likely spread of Lineage IV PPRV strains within the small ruminant population in the region, potentially originating from domestic goats.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"211 ","pages":"Article 108246"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768494","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":"Next-generation biocontrol: The role of antimicrobial peptides in sustainable agriculture","authors":"Jyoti P. Singh ,&nbsp;Jyotsana Tilgam ,&nbsp;Bhavyasree R.K. ,&nbsp;Adarsh Kumar ,&nbsp;Shobit Thapa ,&nbsp;Ritu Vishwakarma ,&nbsp;Rashmi Pandey ,&nbsp;Jaygendra Kumar ,&nbsp;Mahesh Kumar ,&nbsp;Abhijeet S. Kashyap ,&nbsp;Alok K. Srivastava","doi":"10.1016/j.micpath.2025.108252","DOIUrl":"10.1016/j.micpath.2025.108252","url":null,"abstract":"<div><div>Antibiotics have long been used in treating diseases caused by pathogens. However, their extensive and continuous use has led to developing resistance to pathogens, posing risks to plants and ultimately the environment. This challenge underscores the urgent need for innovative antimicrobial agents. Antimicrobial peptides (AMPs) offer an advantageous approach and are crucial for innate host defence. They are appropriate because of their specificity and efficacy as the first line of defence against bacteria, viruses, and fungi. AMPs are produced naturally by both prokaryotes and eukaryotes, posing no environmental threat. AMPs have gained much attention as potential therapies for multidrug-resistant bacteria due to the rise in antibiotic resistance. This review presents recent advances and applications of antimicrobial peptides (AMPs) in agriculture and allied sectors. We also highlight their origins, structures, classifications, mechanisms of action, and potential strategies for increasing their production. Additionally, we discuss the widespread use of AMPs, addressing associated concerns and challenges, along with possible solutions. A comprehensive understanding and application of environmentally friendly biological agents, such as antimicrobial peptides (AMPs), could help address issues like antimicrobial resistance (AMR).</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"211 ","pages":"Article 108252"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145805030","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":"Immunomodulatory effects of the TIRAP/MAL rs8177374 (S180L) variant: Meta-Analytic evidence from severe and Plasmodium falciparum malaria","authors":"Noelia Ivett González-Castillo ,&nbsp;Sandra Guadalupe Prado-Rodríguez ,&nbsp;Omar Iñiguez-Mosqueda ,&nbsp;Liliana Íñiguez-Gutiérrez ,&nbsp;Jorge Manuel Silva-Jara ,&nbsp;Mariana Díaz-Zaragoza ,&nbsp;Omar Graciano-Machuca","doi":"10.1016/j.micpath.2025.108226","DOIUrl":"10.1016/j.micpath.2025.108226","url":null,"abstract":"<div><h3>Background</h3><div>The rs8177374 (S180L) polymorphism in <em>TIRAP</em> has been implicated in altered susceptibility to various infectious diseases, including malaria, though results across studies have been inconsistent.</div></div><div><h3>Objective</h3><div>To systematically review and meta-analyze the association between the TIRAP/MAL rs8177374 polymorphism and malaria susceptibility, including severe malaria and <em>Plasmodium falciparum</em> infection.</div></div><div><h3>Methods</h3><div>A systematic search of PubMed, Scopus, and Web of Science was conducted up to December 31, 2024, without language or geographic restrictions. Case-control and cohort studies reporting genotype and allele frequencies of rs8177374 in malaria patients and controls were included. Studies with control groups deviating from Hardy–Weinberg equilibrium were excluded. Two reviewers independently screened records, extracted data, and assessed study quality using the Newcastle–Ottawa Scale. Pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated under six genetic models using fixed- or random-effects meta-analyses. Heterogeneity was assessed with Cochran's Q and I² statistics. Sensitivity analyses were performed using a leave-one-out approach. Publication bias was assessed using Egger's and Begg's tests.</div></div><div><h3>Results</h3><div>Ten studies comprising 4103 malaria cases and 2460 controls were included. No significant association was observed between rs8177374 and overall malaria susceptibility under any genetic model. In contrast, the T allele and heterozygous genotypes (TC) were consistently associated with a lower risk of severe malaria (T vs. C: OR = 0.51, 95 % CI: 0.40–0.65, <em>p</em> &lt; 0.001). Conversely, in the P. falciparum subgroup, the variant was linked to an increased risk of infection (T vs. C: OR = 1.47, 95 % CI: 1.09–1.98, <em>p</em> = 0.012). Sensitivity analyses confirmed the stability of these associations, and no single study significantly influenced the pooled estimates.</div></div><div><h3>Limitations</h3><div>Limited number of studies in subgroup analyses, high heterogeneity in several comparisons, and geographic restriction to Asian and African populations.</div></div><div><h3>Conclusions</h3><div>The rs8177374 polymorphism is not associated with overall malaria or <em>P. falciparum</em> malaria, but shows a protective effect against severe malaria. These results support a modulatory role of TIRAP/MAL in malaria pathogenesis and warrant further functional and multi-ethnic studies.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"211 ","pages":"Article 108226"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696251","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":"Corrigendum to “Bacillus velezensis LG37 protects Macrobrachium rosenbergii from ammonia nitrogen stress” [Microb. Pathog. 209 (2025) 108098]","authors":"Guangxin Liu ,&nbsp;Hejun Jian ,&nbsp;Anfeng Liu ,&nbsp;Ce Li ,&nbsp;Yiqin Deng ,&nbsp;Sigang Fan ,&nbsp;Hongling Ma ,&nbsp;Changhong Cheng ,&nbsp;Jianjun Jiang ,&nbsp;Juan Feng ,&nbsp;Zhendong Qin ,&nbsp;Zhixun Guo","doi":"10.1016/j.micpath.2025.108227","DOIUrl":"10.1016/j.micpath.2025.108227","url":null,"abstract":"","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"211 ","pages":"Article 108227"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743168","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":"Secnidazole and metronidazole in the treatment of Trichomoniasis: Comparative study of the mechanism of action and development of innovative 3D printed intrauterine devices","authors":"Ágata Giuseppe Menezes ,&nbsp;Fernanda Gomes Cardoso ,&nbsp;Giulia Bongiorni Galego ,&nbsp;Lenon Machado Alves ,&nbsp;Marcelo Dutra Arbo ,&nbsp;Solange Cristina Garcia ,&nbsp;Maiara Callegaro Velho ,&nbsp;Janine Boniatti ,&nbsp;Ruy Carlos Ruver Beck ,&nbsp;Tiana Tasca","doi":"10.1016/j.micpath.2025.108222","DOIUrl":"10.1016/j.micpath.2025.108222","url":null,"abstract":"<div><div><em>Trichomonas vaginalis</em> is the causative agent of trichomoniasis, the most prevalent non-viral sexually transmitted infection (STI) worldwide. This study aimed to evaluate the susceptibility of five <em>T. vaginalis</em> isolates to secnidazole and metronidazole – two of the three FDA-approved treatments. We also investigated their mechanisms of action and explored the use of 3D printing technology for delivering anti-<em>T. vaginalis</em> therapy. <em>In vitro</em> susceptibility assays were performed using secnidazole and metronidazole. To investigate their mechanisms of action, we assessed reactive oxygen and nitrogen species (ROS/RNS) production, lipid peroxidation, type of cell death, and superoxide dismutase (SOD) gene expression by qRT-PCR. DNA integrity was evaluated using the comet assay. Additionally, we designed 3D-printed intrauterine devices (IUDs) loaded with each drug to evaluate their efficacy in eradicating <em>T. vaginalis</em>. All isolates were more susceptible to secnidazole than to metronidazole. Neither drug increased ROS/RNS levels or lipid peroxidation. However, both downregulated SOD expression in most isolates and induced apoptosis-like cell death, evidenced by phosphatidylserine exposure. No DNA strand breaks were detected. Drug-loaded 3D-printed IUDs eradicated <em>T. vaginalis</em> trophozoites within 24 h, with secnidazole achieving this effect as early as 10 h post-treatment. Secnidazole and metronidazole appear to disrupt redox homeostasis through a mechanism independent of ROS/RNS, likely by downregulating SOD and increasing cellular susceptibility to oxidative stress. Both drugs induced apoptosis-like cell death without causing DNA damage. The drug-loaded devices represent a promising strategy for localized and personalized treatment. This is the first proof-of-concept for a 3D-printed IUD loaded with secnidazole and metronidazole demonstrating trichomonacidal action and highlighting a novel, localized drug delivery strategy with potential applications in personalized medicine for the treatment of trichomoniasis.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"211 ","pages":"Article 108222"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695686","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":"Phylogenetic, pathotyping and haplotype analysis of Theileria orientalis in crossbred cattle of northern Kerala, India","authors":"Geethu Reghu ,&nbsp;Anju Varghese ,&nbsp;Deepa Chundayil Kalarickal ,&nbsp;Ajith Kumar Karapparambu Gopalan ,&nbsp;Shiji Thozhukkad Moosaripparambil ,&nbsp;Anaswara Aravindakshan ,&nbsp;Sreenidhi Nellikka Chalapron ,&nbsp;Renjith Sebastian ,&nbsp;Biju Peer Habeeb ,&nbsp;Arun Chungapally ,&nbsp;Reghu Ravindran","doi":"10.1016/j.micpath.2025.108235","DOIUrl":"10.1016/j.micpath.2025.108235","url":null,"abstract":"<div><div><em>Theileria orientalis</em>, previously considered non-pathogenic, has recently been associated with clinical outbreaks of theileriosis in India, posing a significant threat to the dairy industry. This study aimed to determine the prevalence and haplotype diversity of <em>T. orientalis</em> in crossbred cattle in northern Kerala and to unravel the potential associations between haplotypes and clinical disease. Blood samples were collected from 149 crossbred cattle in areas with history of <em>Theileria</em> outbreaks and high tick infestation in northern Kerala and screened by microscopy and molecular methods. Piroplasms were detected in 78 (52.3 %) of Giemsa-stained blood smears. Further, conventional PCR targeting ∼776 base pair of the major piroplasm surface protein (<em>MPSP</em>) gene successfully amplified the DNA of <em>T. orientalis</em> in 124 (83.4 %) of the samples. Infected adults exhibited macrocytic normochromic anaemia, whereas infected calves had normocytic hypochromic anaemia. Red blood cell count, haematocrit, and haemoglobin levels did not differ significantly between infected and non-infected cattle. However, eosinophil and reticulocyte counts were significantly higher in infected animals (p &lt; 0.001). The positive animals were categorized into four groups (Group I-IV) based on haematological findings, microscopy, and PCR results. Phylogenetic and network analyses of the <em>MPSP</em> gene revealed the presence of genotypes 3, 5, and 7 in the present study, with genotype 5 reported for the first time from Kerala and being the most prevalent (47.05 %). A total of 43 distinct haplotypes were identified, with genotype 5 being the most diverse. A distinct age-related distribution of <em>T. orientalis</em> genotypes was observed, with type 7 occurring predominantly in calves and type 5 in adults. However, the genotype 7 generally regarded as a pathogenic was also detected in asymptomatic calves as well as in anaemic animals. Insights into genetic diversity, age-related susceptibility, and host responses are vital for developing effective surveillance, targeted control strategies, and sustainable management of the oriental theileriosis.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"211 ","pages":"Article 108235"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743215","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 Vyarna Bio Information Booster: Maximization of microbiome bioinformation diversity through the combination of the lyophilized human breast milk of multiple providers","authors":"Pedro Alvarado Chavarría ,&nbsp;Faisal Sheraz Shah ,&nbsp;Amna Hafeez ,&nbsp;Sameen Zafar ,&nbsp;Khushbukhat Khan","doi":"10.1016/j.micpath.2025.108243","DOIUrl":"10.1016/j.micpath.2025.108243","url":null,"abstract":"<div><div>Human breast milk is increasingly recognized not only as nourishment but as a dynamic medium of biological information—delivering nutrients, immune molecules, and microbial ecosystems critical to early development. While each mother transmits a unique immunological and microbiota profile, the developmental impact of amplifying this diversity remains unexplored. Here, we introduce the Vyarna Booster: a novel, shelf-stable powder formed by combining lyophilized breast milk from multiple verified providers to intentionally exceed the microbial diversity found in any single sample. Using 16S rRNA gene sequencing, we analyzed bacterial composition across fresh (F), individually lyophilized (L), and mixed composite (M) samples from 13 mothers. The composite formulation exhibited greater microbial richness and evenness than any source sample, with consistently elevated abundance of commensals such as <em>Streptococcus salivarius</em> and <em>Lactococcus raffinolactis</em>. This increased diversity was reproducible across independently assembled mixes. While we do not claim viability or clinical outcomes, the observed taxonomic amplification suggests a previously untested mechanism for engineering postnatal microbial exposure. We propose the Vyarna Booster as a new class of infant nutritional supplement—one that augments the natural limits of human milk through deliberate bioinformational combination, and raises foundational questions about the boundaries of maternal transmission, microbial design, and early life programming.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"211 ","pages":"Article 108243"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794339","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":"Salmonella Typhimurium StiP-mediated upregulation of membrane protein Alx drives complement evasion via CFI-dependent C3b degradation","authors":"Jin Guan ,&nbsp;ZhouPing Zhou ,&nbsp;Peng Pan ,&nbsp;Kaifeng Chen ,&nbsp;Nanwei Wang ,&nbsp;Weilin Zhuang ,&nbsp;Hailin Fan ,&nbsp;Yixin Tang ,&nbsp;Jiaqi Wan ,&nbsp;Bosen Wang ,&nbsp;Chenggang Xu ,&nbsp;Ming Liao ,&nbsp;Jianmin Zhang","doi":"10.1016/j.micpath.2025.108232","DOIUrl":"10.1016/j.micpath.2025.108232","url":null,"abstract":"<div><div>Invasive <em>Salmonella</em> Typhimurium (<em>S.</em> Typhimurium) causes lethal bloodstream infections (BSI), yet its molecular mechanisms remain unclear. We compared serum resistance and cellular invasive capabilities between invasive and non-invasive <em>S</em>. Typhimurium. Invasive strains exhibited significantly enhanced serum resistance (&gt;17-fold survival in 75 % isolates) and HeLa cell invasive ability (minimum bacterial loads 3.93 × 10⁵ CFU/mL) compared to non-invasive strains (&lt;9.8-fold survival; maximum bacterial loads 1.47 × 10⁵ CFU/mL). We next performed pan-genomic analysis and virulence gene database comparisons to elucidate the genetic mechanisms underlying robust serum resistance in invasive <em>S.</em> Typhimurium. We identified 15 differential genes unique to invasive <em>S.</em> Typhimurium, among which the <em>StiP</em> deletion strain (<em>263ΔStiP</em>) showed the greatest serum resistance reduction (2.49-fold). We further explored the role of <em>StiP</em> in host blood environment adaptation and found that <em>263ΔStiP</em> displayed 3.12-fold reduced HeLa cell adhesion, 3.74-fold lower HeLa cell invasion, 1.92-fold decreased intra-macrophage survival, and 50 % reduced serum resistance versus wild-type 263 (WT263), collectively indicating that <em>StiP</em> is critical for host blood environment adaptation in invasive <em>S</em>. Typhimurium. Mechanistically, <em>StiP</em> upregulates the membrane protein Alx, which recruits complement factor I (CFI) to accelerate C3b degradation, thereby inhibiting classical complement pathway activation and enhancing invasive <em>S.</em> Typhimurium complement evasion. <em>In vivo</em>, 263<em>ΔStiP</em>-infected mice exhibited 5-, 7-, and 4-fold lower bacterial loads in blood, liver, and spleen (P &lt; 0.001), respectively, with reduced pathological damage versus WT263. Thus, this study elucidates the <em>StiP</em>-Alx axis mediating complement evasion in invasive <em>S.</em> Typhimurium.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"211 ","pages":"Article 108232"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145724599","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}