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Iskalni niz: "ključne besede" (antibiotic resistance) .

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1.
Insights into diversity, host-range, and temporal stability of Bacteroides and Phocaeicola prophages
Nejc Stopnišek, Stina Hedžet, Tomaž Accetto, Maja Rupnik, 2025, izvirni znanstveni članek

Povzetek: Background Phages are critical components of the gut microbiome, influencing bacterial composition and function as predators, parasites, and modulators of bacterial phenotypes. Prophages, integrated forms of these phages, are prevalent in many bacterial genomes and play a role in bacterial adaptation and evolution. However, the diversity and stability of prophages within gut commensals, particularly in the genera Bacteroides and Phocaeicola, remain underexplored. This study aims to screen and characterize prophages in these genera, providing insights into their diversity, host range, and temporal dynamics in the human gut. Results Using a combination of three bioinformatic tools—Cenote-Taker 3, Vibrant, and PHASTER—we conducted a comprehensive analysis of prophages in Bacteroides and Phocaeicola. Cenote-Taker 3 identified the most diverse set of prophages, with significant overlaps observed between the tools. After clustering high-quality prophages, we identified 22 unique viral operational taxonomic units (vOTUs). Notably, comparisons between prophages identified in isolated bacterial genomes, metaviromes, and large public gut virome databases revealed a broader host range than initially observed in single isolates. Certain prophages were consistent across time points and individuals, suggesting temporal stability. All identified prophages belonged to the Caudoviricetes class and contained genes related to antibiotic resistance, toxin production, and metabolic processes. Conclusions The combined use of multiple prophage detection tools allowed for a more comprehensive assessment of prophage diversity in Bacteroides and Phocaeicola. The identified prophages were not only prevalent but also exhibited broad host ranges and temporal stability. The presence of antibiotic resistance and toxin genes suggests that these prophages may significantly influence bacterial community structure and function in the gut, with potential implications for human health. These findings highlight the importance of using diverse detection tools to accurately assess prophage diversity and dynamics.
Ključne besede: prophage detection, Bacteroides, Phocaeicola, gut microbiome, prophage diversity, Caudoviricetes, antibiotic resistance, phage-bacteria interactions, temporal stability
Objavljeno v DiRROS: 06.03.2025; Ogledov: 181; Prenosov: 165
.pdf Celotno besedilo (1,73 MB)
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2.
Non-clinical in vitro evaluation of antibiotic resistance gene-free plasmids encoding human or murine IL-12 intended for first-in-human clinical study
Špela Kos, Maša Omerzel, Tanja Jesenko, Boštjan Markelc, Urška Kamenšek, Katarina Žnidar, Urška Matkovič, Andrej Renčelj, Gregor Serša, Rosana Hudej, Aneja Tuljak, Matjaž Peterka, Maja Čemažar, 2021, izvirni znanstveni članek

Povzetek: Interleukin 12 (IL-12) is a key cytokine that mediates antitumor activity of immune cells. To fulfill its clinical potential, the development is focused on localized delivery systems, such as gene electrotransfer, which can provide localized delivery of IL-12 to the tumor microenvironment. Gene electrotransfer of the plasmid encoding human IL-12 is already in clinical trials in USA, demonstrating positive results in the treatment of melanoma patients. To comply with EU regulatory requirements for clinical application, which recommend the use of antibiotic resistance gene-free plasmids, we constructed and developed the production process for the clinical grade quality antibiotic resistance gene-free plasmid encoding human IL-12 (p21-hIL-12-ORT) and its ortholog encoding murine IL-12 (p21-mIL-12-ORT). To demonstrate the suitability of the p21-hIL-12-ORT or p21-mIL-12-ORT plasmid for the first-in-human clinical trial, the biological activity of the expressed transgene, its level of expression and plasmid copy number were determined in vitro in the human squamous cell carcinoma cell line FaDu and the murine colon carcinoma cell line CT26. The results of the non-clinical evaluation in vitro set the basis for further in vivo testing and evaluation of antitumor activity of therapeutic molecules in murine models as well as provide crucial data for further clinical trials of the constructed antibiotic resistance gene-free plasmid in humans.
Ključne besede: interleukin 12, gene electrotransfer, antibiotic resistance, plasmids
Objavljeno v DiRROS: 07.09.2022; Ogledov: 1181; Prenosov: 623
.pdf Celotno besedilo (4,73 MB)
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