The effects of bacteriophage cocktail treatment on healthy gut microbiota: an in vitro human colon model
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PROVIDER: PRJEB96854 | ENA |
REPOSITORIES: ENA
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Project description:Acinetobacter baumannii is currently a major threat to human health. With the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, the development of complementary strategies is needed. A promising complimentary and realistic strategy could be phage therapy, which uses bacteriophages (phages), i.e viruses that specifically infect and kill bacterial cells during their life cycle. We designed a two-phage cocktail highly efficient against an extensive drug-resistant (XDR) A. baumannii isolate collected from a patient with burn wound infection at CHUV (termed Ab125). A first in vitro screen of our collection of 34 different phages identified only phage vB_AbaM_3098 as capable of lysing Ab125. However, quick selection of phage-resistant clones (termed Ab139) occurred. Comparative genomics and proteomics between Ab125 and Ab139 revealed several key variations. Very interestingly, we observed that Ab139 became susceptible to six different phages in the collection, otherwise inactive on Ab125. Phage-resistance was also selected when Ab139 was challenged with either of the six phages, with bacterial regrowth observed between 14 h and 16 h. However, combination of vB_AbaM_3098 and vB_AbaM_3014 led to a two-phage cocktail capable of totally inhibiting the growth of Ab125. Treatment with the phage cocktail led to 90% survival after 5 days in the in vivo Galleria Mellonella model of infectious diseases, compared to 0% in the non-treated group. We show that the combination of a phage that only slightly shifted the in vitro bacterial growth curve with an “inactive phage” led to the formulation of a highly bactericidal phage cocktail against Ab125. We then tested the therapeutic potential of the assembled cocktail in synergy with antibiotics and found a synergy with colistin. This work highlights the complexity sometimes involved in the assembly of potent phage cocktail.
2025-12-08 | PXD062593 | Pride
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Project description:Capsule is a critical virulence factor that significantly contributes to phage resistance in Acinetobacter baumannii. To investigate the interplay between capsule-based defense and phage predation, we applied phage selection pressure to A. baumannii to generate isogenic phage-resistant mutants. Utilizing transcriptomic analysis, we subsequently characterized the global alterations in the biological regulatory network of a capsule-deficient, phage-resistant mutant in comparison to its parental strain. This approach allowed us to identify key transcriptional reprogramming events associated with the acquisition of phage resistance in the absence of a functional capsule.
2025-10-01 | GSE308794 | GEO
Project description:A study to develop a therapeutic phage cocktail against ESBL urinary tract infection clinical isolates of Klebsiella and E.coli
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Project description:Background & Aims: We have recently established long-term culture conditions under which single crypts or stem cells derived from murine small intestine expand over long periods of time. Growing crypts undergo multiple crypt fission events, whilst simultaneously generating villus-like epithelial domains in which all differentiated cell types are present. We have now adapted the culture conditions to grow similar epithelial organoids from mouse colon and human small intestine and colon. Methods: Based on the murine small intestinal culture system, we optimized the murine and human colon culture system. Results: Addition of Wnt3A to the growth factor cocktail allowed mouse colon crypts to expand indefinitely. Further addition of nicotinamide, a small molecule Alk inhibitor and a p38 inhibitor was essential for long-term human small intestine and colon culture. The culture system also allowed growth of murine Apcmin adenomas, human colorectal cancer and human esophageal metaplastic Barrett’s epithelium. Conclusion: The culture technology should be widely applicable as a research tool for infectious, inflammatory and neoplastic pathologies of the human gastrointestinal tract. Moreover, regenerative applications may become feasible with ex vivo expanded intestinal epithelia.
2011-12-07 | GSE28907 | GEO
Project description:Phage therapy has garnered significant attention due to the rise of life-threatening multidrug-resistant pathogenic bacteria and the growing awareness of the transfer of resistance genes between pathogens. In light of this, phage therapy applications are now being extended to target plant pathogenic bacteria, like Erwinia amylovora that causes fire blight in apple and pear orchards. Understanding the mechanisms of phage resistance development is crucial for enhancing the effectiveness of phage therapy. Despite the challenges of naturally developing a bacteriophage resistant mutant (BIM) of E. amylovora (without traditional mutagenesis methods), this study successfully created a BIM mutant against the podovirus Ea46-1-A1. The parent strain, E. amylovora D7, and the BIM mutant, B6-2 were compared at the transcriptomic level.
2025-12-09 | GSE291879 | GEO
Project description:The gut microbiota is increasingly recognized as an important modulator of human health. As such, there is a growing need to identify effective means of selectively modifying gut microbial communities. Bacteriophages, which were briefly utilized as clinical antimicrobials in the early 20th century, present an opportunity to selectively reduce populations of undesirable microorganisms. However, whether intentional consumption of specific bacteriophages affects overall gut ecology is not yet known. Using a commercial cocktail of Escherichia coli-targeting bacteriophages, we examined their effects on gut microbiota and markers of intestinal and systemic inflammation in a healthy human population. In a double-blinded, placebo-controlled crossover trial, normal to overweight adults consumed bacteriophages for 28 days. Stool and blood samples were collected and used to examine inflammatory markers, lipid metabolism, and gut microbiota. Reductions in fecal E. coli loads were observed with phage consumption. However, there were no significant changes to alpha and beta diversity parameters, suggesting that consumed phages did not globally disrupt the microbiota. However, specific populations were altered in response to treatment, including increases in members of the butyrate-producing genera Eubacterium and a decreased proportion of taxa most closely related to Clostridium perfringens. Short-chain fatty acid production, inflammatory markers, and lipid metabolism were largely unaltered, but there was a small but significant decrease in circulating interleukin-4 (Il-4). Together, these data demonstrate the potential of bacteriophages to selectively reduce target organisms without global disruption of the gut community.
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Project description:Here, we used bulk RNA-seq data derived from healthy colon organoids (un)exposed to aspirin. Through the use of external single cell RNA-seq data, we estimate changes in cell composition. We extend this analysis by controlling for cell composition and performing WGCNA to identify modules of co-expression differentially affected by aspirin treatment in colon organoids.
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Project description:Low-quality oocytes directly affect fertilization and embryo developmental ability, and further contributes to infertility in women. Dasatinib and quercetin, as a senolytics, has been explored extensively in various age-related diseases. Here, we report that nano-encapsulated senolytics cocktail (D+Q) efficaciously ameliorates the the quantity and quality of follicles and oocytes in vitro and in vivo. D+Q cocktail supplementation reduces the level of ROS in aged oocytes, decreases the frequency of fragmentation, maintains the spindle integrity, rescues mislocalized cortical granules, rescues mitochondrial membrane potential and alleviates DNA damage and apoptosis in vitro. Nano-encapsulated D+Q cocktail effectively ameliorates the fertility deficits in the cyclophosphamide-induced primary ovarian failure (POF) mice model. Moreover, RNA sequencing analysis shows that D+Q cocktail improves the fecundity of POF mice by increasing development gene expression and reduces the senescence-associated secretory phenotype (SASP) accumulation. Taken together, our data show that the D+Q cocktail helps to improve assisted reproductive technology and reproductive outcomes in POF.
2024-04-23 | GSE264327 | GEO