Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1175678 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This study aims to determine the epidemiology of Enterobacteriaceae resistant to antibiotics of last resort in pregnant women in labour at a tertiary hospital, Pretoria, South Africa. Rectal swabs shall be used to screen for colonisation with CRE and colistin-resistant Enterobacteriales in pregnant women during labour. Carbapenem and colistin-resistant Enterobacterales can cause the following infections: bacteraemia; nosocomial pneumonia; urinary tract infections, and intra-abdominal infections. Due to limited treatment options, infections caused by these multidrug-resistant organisms are associated with a mortality rate of 40-50%. Screening for colonisation of carbapenem-resistant Enterobacteriaceae (CRE) and colistin-resistant Enterobacteriaceae will help implement infection and prevention measures to limit the spread of these multidrug-resistant organisms.
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Project description:<p>Diabetic foot infection (DFI) significantly increases risks of hospitalization and amputation, with biofilm infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Enterobacteriaceae (CRE) being key drivers of treatment failure. Here, we analyze MRSA/CRE biofilm-infected ulcer tissues in patients using proteomics and metabolomics. Compared to non-healing cases, healed tissues show activation of the low-density lipoprotein receptor (LDLR)-mediated low-density lipoprotein cholesterol (LDL-C) endocytosis and increase free fatty acids production, which we hypothesize a potential countermeasure against biofilms. However, free fatty acids’ oxidative instability limits their therapeutic use. Building on our findings demonstrating Rhein’s potent anti-MRSA/CRE activity and its synergy with Ag⁺, we develop an injectable hydrogel for sustained co-delivery of both agents. This formulation outperforms Ag⁺ monotherapy, accelerating wound closure in biofilm-infected diabetic wounds. Mechanistically, Rhein binds to LDLR, upregulates its expression, and enhances LDL-C endocytosis pathway in vascular endothelial cells to generate more free fatty acids. Among these, eicosapentaenoic acid (EPA) is identified as the most critical free fatty acids promoting healing, as it inhibits biofilm formation and synergizes with Ag⁺ to exert antibacterial and pro-healing effects. Collectively, this study identifies endogenous host lipid metabolites as “metabolic antibiotics” and establishes a synergistic therapeutic strategy that concurrently suppresses biofilm formation, inhibits planktonic bacteria, alleviates inflammation, and promotes tissue repair in drug-resistant biofilm infected diabetic wounds.</p>
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Project description:carbapenem resistant klebsiella pneumoniae in Egypt
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Project description:<p>Diabetic foot infection (DFI) significantly increases risks of hospitalization and amputation, with biofilm infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Enterobacteriaceae (CRE) being key drivers of treatment failure. Here, we analyze MRSA/CRE biofilm-infected ulcer tissues in patients using proteomics and metabolomics. Compared to non-healing cases, healed tissues show activation of the low-density lipoprotein receptor (LDLR)-mediated low-density lipoprotein cholesterol (LDL-C) endocytosis and increase free fatty acids production, which we hypothesize a potential countermeasure against biofilms. However, free fatty acids’ oxidative instability limits their therapeutic use. Building on our findings demonstrating Rhein’s potent anti-MRSA/CRE activity and its synergy with Ag⁺, we develop an injectable hydrogel for sustained co-delivery of both agents. This formulation outperforms Ag⁺ monotherapy, accelerating wound closure in biofilm-infected diabetic wounds. Mechanistically, Rhein binds to LDLR, upregulates its expression, and enhances LDL-C endocytosis pathway in vascular endothelial cells to generate more free fatty acids. Among these, eicosapentaenoic acid (EPA) is identified as the most critical free fatty acids promoting healing, as it inhibits biofilm formation and synergizes with Ag⁺ to exert antibacterial and pro-healing effects. Collectively, this study identifies endogenous host lipid metabolites as “metabolic antibiotics” and establishes a synergistic therapeutic strategy that concurrently suppresses biofilm formation, inhibits planktonic bacteria, alleviates inflammation, and promotes tissue repair in drug-resistant biofilm infected diabetic wounds. </p>
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