Gammaproteobacteria
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1090910 | ENA |
REPOSITORIES: ENA
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Project description:The management of antibiotic-resistant, bacterial biofilm infections in chronic skin wounds is a significant clinical challenge. Despite advances in diagnosis, many patients do not derive benefit from current anti-infective/antibiotic therapies. Here we report a novel class of epoxy-tiglianes and demonstrate their antimicrobial activity (modifying bacterial growth and inducing biofilm disruption), with structure/activity relationships established against important human pathogens. In vitro, the lead candidate, EBC-1013 stimulated PKC-dependent neutrophil ROS induction and NETosis, and increased expression of wound healing associated cytokines, chemokines and antimicrobial peptides in keratinocytes and fibroblasts. In vivo, topical EBC-1013 induced rapid resolution of infection with increased matrix remodelling in acute thermal injuries. In chronically-infected, diabetic wounds, treatment induced cytokine/chemokine production, inflammatory cell recruitment and complete healing (in 6/7 wounds) with ordered keratinocyte differentiation. These results highlight a non-antibiotic approach involving contrasting, orthogonal mechanisms of action: targeted biofilm disruption and innate immune induction in the treatment of chronic wounds.
2022-05-14 | GSE202952 | GEO
Project description:The management of antibiotic-resistant, bacterial biofilm infections in chronic skin wounds is a significant clinical challenge. Despite advances in diagnosis, many patients do not derive benefit from current anti-infective/antibiotic therapies. Here we report a novel class of epoxy-tiglianes and demonstrate their antimicrobial activity (modifying bacterial growth and inducing biofilm disruption), with structure/activity relationships established against important human pathogens. In vitro, the lead candidate, EBC-1013 stimulated PKC-dependent neutrophil ROS induction and NETosis, and increased expression of wound healing associated cytokines, chemokines and antimicrobial peptides in keratinocytes and fibroblasts. In vivo, topical EBC-1013 induced rapid resolution of infection with increased matrix remodelling in acute thermal injuries. In chronically-infected, diabetic wounds, treatment induced cytokine/chemokine production, inflammatory cell recruitment and complete healing (in 6/7 wounds) with ordered keratinocyte differentiation. These results highlight a non-antibiotic approach involving contrasting, orthogonal mechanisms of action: targeted biofilm disruption and innate immune induction in the treatment of chronic wounds.
2022-05-12 | GSE202794 | GEO
Project description:Combat veterans from the Persian Gulf War have unexplained yet persistent impairment in colonic motility due to combat-related toxic exposures. Central to Gulf War-related toxic exposures was the unmitigated ingestion of Pyridostigmine bromide (PB). We previously developed a Gulf War Illness (GWI) mouse model, where acute PB exposure led to immediate disruptions in colonic motility. Here, we explore mechanisms by which acute enteric neuroinflammation produces peristent impairment in colonic motility. GWI mice were exposed to PB transiently, and allowed to recover with no exposures for 1 month. GWI mice had significantly increased amplitudes of colonic contraction and diminished nerve-stimulated colonic relaxation, compared to naive controls. Immunohistological characterization demonstrated persistent chronic damage in enteric neuronal network integrity, accompanied by a significant imbalance in excitatory and inhibitory motor neuronal populations. Inflammatory CD40+ tissue- resident macrophages were identified with enteric neural stem cells in GWI colons, with an increase in secreted inflammatory cytokines. Unbiased transcriptomic analysis corroborated peristent low grade enteric neuroinflammation, overall resulting in impaired repair and regeneration of neural circuity in GWI. Our learnings can be leveraged to design new regenerative therapies for Gulf War veterans, and broadly impact our understanding of severeal inflammatory disorders of the gut.
2024-09-07 | GSE276269 | GEO
Project description:Infected wounds pose a major mortality risk in animals. Injuries are particularly common in the ant Megaponera analis which raids pugnacious prey. Here we show that M. analis can determine when wounds are infected and treat them specifically. By applying a variety of antimicrobial compounds and proteins secreted from the metapleural gland to infected wounds workers reduce the mortality of infected individuals by 90%. Chemical analyses showed that wound infection is associated with specific changes in the cuticular hydrocarbon profile thereby likely allowing nestmates to diagnose the infection state of injured individuals and apply the appropriate antimicrobial treatment. This study demonstrates that the targeted use of antimicrobials to treat infected wounds, previously thought to be a uniquely human behavior, has evolved in insect societies as well.
2023-12-05 | PXD033003 | Pride
Project description:Adult mammalian skin wound healing is typically accompanied by a fibrotic scar that impairs normal skin function and regeneration of skin appendages. Interestingly, however, in adult mice, large skin injuries exhibit de novo formation of hair follicles (HFs, a phenomenon termed wound-induced HF neogenesis) in the center of the wound. Our previous analysis provides compelling evidence suggesting that regional epigenetic changes within the mesenchymal cells of the skin may underlie the divergent response to wound healing. To test this directly, we performed single-cell Assay for Transposase-Accessible Chromatin using Sequencing (sc-ATAC-Seq) on cells isolated from the center of large wounds to identify regions of the genome that are becoming differentially accessible within upper (epithelial-interfacing) fibroblasts as they transition to induce new HFs compared to their lower dermal counterparts that adopt a fibrotic phenotype. Together, our data reveals the identity and dynamics of key coding, non-coding, and regulatory regions that underlie a wound responsive fibroblasts' transition to inductive neodermal condensate cells.
2020-08-04 | GSE131600 | GEO
Project description:Gene expression analysis in response to mechanical injuries in Pinus canariensis, known for a great healing ability. Traumatic xylem formed in the margins of the wounds were compared to control tissues, sampled from remote parts of the plant, in order to check transcriptomical variations in three dates during the response: H1, H2 and H3 for 7, 78 and 92 days after wounding.
2017-10-26 | GSE102275 | GEO
Project description:Molecular epidemiology of multidrug-resistant bacteria isolated from Libyan and Syrian patients with war injuries
| PRJNA407760 | ENA