https://hdl.handle.net/20.500.14178/1 Faculties Tue, 14 Apr 2026 17:53:55 GMT 2026-04-14T17:53:55Z https://hdl.handle.net/20.500.14178/3736 Remodeling of the cellular membrane architecture in response to BK polyomavirus infection Bruštíková, Kateřina; Forstová, Jitka; Holajová, Barbora; Huerfano Meneses, Sandra BK polyomavirus (BKPyV) is a human pathogen that causes severe disease in immunocompromised individuals. Although discovered in the 1970s, important gaps in our understanding of BKPyV biology persist. Key unresolved areas include the precise molecular mechanisms governing viral latency and reactivation, the specific host and viral factors determining the virus tropism towards the urinary track, and the intricate virus-host interactions that drive clinical pathogenesis. These unresolved biological questions have stalled the development of targeted therapeutics; as a result, no specific antiviral therapy is currently available for BKPyV-related diseases. In this review, we examined findings from both experimental models and clinical samples that investigate how BKPyV remodels host organelles and the molecular pathways underlying these alterations. We focus on BKPyV-driven changes in cellular membranes, including endoplasmic reticulum remodeling, mitochondrial disruption, the formation of endoplasmic reticulum-derived tubuloreticular structures, vacuoles, and autophagosomes, as well as the accumulation of lipid droplets. Collectively, these organelle-specific modifications highlight membrane remodeling as a central feature of BKPyV replication and pathogenesis. Addressing the key knowledge gaps in the molecular basis of virus-induced membrane remodeling will be critical for guiding the development of effective antiviral strategies. Thu, 01 Jan 2026 00:00:00 GMT https://hdl.handle.net/20.500.14178/3736 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3735 Dynamic changes in the plasmidome and resistome in the gastrointestinal tract of chickens Ryšavá, Markéta; Stredanska, Katarina; Schwarzerova, Jana; Jakubickova, Marketa; Cejkova, Darina; Aytan-Aktug, Derya; Otani, Saria; Dolejská, Monika; Palkovičová, Jana The expansion of intensive poultry farming has led to a substantial increase in antibiotic use, which, in turn, has promoted the accumulation of antibiotic resistance genes (ARGs). The chicken gut serves as a reservoir for these genes and provides favorable conditions for their horizontal transfer via mobile genetic elements, such as plasmids. Through this process, commensal bacteria can transfer ARGs to pathogens, facilitating their spread and increasing the risk of transmission to humans. In this study, long-read sequencing was used to characterize the plasmidome and resistome in 12 fecal samples from 3 houses of a commercial broiler chicken farm. All chickens received enrofloxacin in the first days of life, with one house additionally treated with sulfamethoxazole/trimethoprim combination. For comparison, metagenomic analysis using short-read sequencing was performed on the same samples. This study revealed the presence of various ARGs associated with resistance to 25 antibiotic classes. A strong genetic association between MOBP-type plasmids and fluoroquinolone resistance was observed within broiler chicken farms. Temporal trends indicated progressive mobilization of these ARGs, suggesting an increasing potential for horizontal gene transfer. While fluoroquinolone resistance expanded over time, diaminopyrimidine resistance remained stable despite the antibiotic treatment. Most ARGs were carried on small plasmids, and complete plasmid reconstructions ranged from 2.6 to 47.6 kb. Our findings demonstrate that plasmidome sequencing enables high-resolution detection of resistance-associated plasmids that may be overlooked by conventional metagenomic approaches. The observed patterns are consistent with an association between fluoroquinolone use in poultry farms and the presence of plasmid-mediated resistance genes with potential for horizontal dissemination. Thu, 01 Jan 2026 00:00:00 GMT https://hdl.handle.net/20.500.14178/3735 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3734 Claudin 1 – mediated positioning of DC1 to mTECs is essential for maintenance of central tolerance Březina, Jiří; Brabec, Tomáš; Machač, David; Vobořil, Matouš; Ballek, Ondřej; Pačes, Jan; Sýkora, Vojtěch; Jančovičová, Kristína; Valter, Evgeny; Kováčová, Katarína; Manning, Jasper; Tahtahová, Valerie; Čepková, Adéla; Dobešová, Martina; Dobeš, Jan; Kubovčiak, Jan; Kolář, Michal; Kašpárek, Petr; Sedlacek, Radislav; Štepánek, Ondřej; Černý, Jan; Tsukita, Sachiko; Malissen, Bernard; Anderson, Graham; Filipp, Dominik Central tolerance, which relies on the presentation of self-antigens by mTECs and DCs, prevents autoimmunity by eliminating self-reactive T cells. While mTECs produce self-antigens autonomously, DCs acquire them from mTECs via cooperative antigen transfer (CAT). We previously showed that mTEC and DC subsets exhibit preferential pairing in CAT, providing a rationale for the existence of molecular determinants underpinning this pairing and its outcome. Here, we compared the transcriptomes of CAT-experienced and CAT-inexperienced DCs and identified Claudin 1 as a molecule involved in CAT and type 1 DC (DC1) maturation. DC1-specific ablation of Claudin 1 resulted in decreased CAT to late mature DC1s and dramatically diminished DC1 maturation. These phenotypes correlated with the displacement of DC1s from mTECs and their decreased expression of MHCII pathway genes. This translated into impaired Treg selection and clonal deletion, ultimately manifesting in symptoms of multiorgan autoimmunity and shortened lifespan. Collectively, our results identify thymic DC1-derived Claudin 1 as a regulator of immune tolerance. Thu, 01 Jan 2026 00:00:00 GMT https://hdl.handle.net/20.500.14178/3734 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3733 Unraveling the telomere-mitochondrial axis in colorectal cancer: Results from a prospectively followed cohort Gil-Korilis, Adrián; Ergui-Arbizu, Jorge; Hanák, Petr; Danešová, Natálie; Tomášová, Kristýna; Valíčková, Anna; Horák, Josef; Gentiluomo, Manuel; Levý, Miroslav; Křivonosková, Soňa; Král, Jan; Jungwirth, Jiří; Vodičková, Ľudmila; Vymetálková, Veronika; Azqueta, Amaya; Campa, Daniele; Vodička, Pavel; Vodenková, Soňa Background Telomere shortening and mitochondrial dysfunction are well-known independent contributors to many diseases, but emerging evidence suggests a reciprocal relationship between the two processes. The role of the so-called telomere-mitochondrial axis in colorectal cancer (CRC) remains largely unknown. Methods This prospective cohort study screened CRC patients who underwent surgery, from whom peripheral blood, intestinal mucosa, and tumor samples were collected. Colonoscopically confirmed cancer- and adenoma-free healthy individuals were screened as controls, from whom peripheral blood and intestinal mucosa samples were obtained. Relative mitochondrial DNA copy number (mtDNA-CN) and relative telomere length (RTL) were measured in all samples by real-time quantitative polymerase chain reaction and were further compared and correlated considering clinical data. Relative mtDNA-CN was quantified using both TaqMan probes and SYBR Green to compare both methods. Finally, multivariable analyses were conducted to investigate the association between both biomarkers and the risk of tumor recurrence and mortality. Results A total of 166 CRC patients and 61 healthy individuals were included in the study. In TNM stage I patients, relative mtDNA-CN and RTL were negatively correlated with each other in intestinal mucosa (ρ = -0.77, p < 0.0001), tumor tissue (ρ = -0.41, p = 0.032), and the tumor-to-intestinal mucosa ratio (ρ = -0.39, p = 0.046). However, these associations disappeared with increasing TNM stage, suggesting a dysregulation of the telomere-mitochondrial axis in advanced disease. Higher relative mtDNA-CN in blood was associated with a lower risk of disease recurrence even after adjusting for multiple covariates (HR = 0.43, 95% CI 0.20-0.97, p = 0.041), highlighting its potential use as a prognostic tool. The quantification of mtDNA-CN performed by both methods -TaqMan probes and SYBR Green- was shown to be positively correlated (p < 0.01). Relative mtDNA-CN and RTL were found to be tissue-dependent in both CRC patients and healthy controls. Conclusions This study provides a novel contribution to the understanding of the almost unexplored telomere-mitochondrial axis in CRC, highlighting its potential role in disease progression and prognosis. Thu, 01 Jan 2026 00:00:00 GMT https://hdl.handle.net/20.500.14178/3733 2026-01-01T00:00:00Z