Fatty acids are a primary source of carbon for Pseudomonas aeruginosa (PA) in the airways of people with cystic fibrosis (CF). Here, we use tandem mass-tag proteomics to analyse the protein expression profile of a CF clinical isolate grown on different fatty acids. Two fatty acyl-CoA dehydrogenases (designated FadE1 and FadE2) are strongly induced during growth on fatty acids. FadE1 displays a strong preference for long-chain acyl-CoAs, whereas FadE2 exclusively utilizes medium-chain acyl-CoAs. Structural analysis of the enzymes enables us to identify residues comprising the substrate selectivity filter in each. Engineering these residues enables us to invert the substrate specificity of each enzyme. Mutants in fadE1 displayed impaired virulence in an infection model, and decreased growth on long chain fatty acids. The unique features of the substrate binding pocket enable us to identify an inhibitor that is differentially active against FadE1 and FadE2.
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http://dx.doi.org/10.1038/s41467-025-57532-z | DOI Listing |
Cells
February 2025
Department of Gastroenterology and Internal Medicine, Medical University of Bialystok, 15-276 Bialystok, Poland.
An association between gut microbiota and the development of pancreatic ductal adenocarcinoma (PDAC) has been previously described. To better understand the bacterial microbiota changes accompanying PDAC promotion and progression stimulated by inflammation and fecal microbiota transplantation (FMT), we investigated stool and pancreatic microbiota by 16s RNA-based metagenomic analysis in mice with inducible acinar transgenic expressions of KrasG12D, and age- and sex-matched control mice that were exposed to inflammatory stimuli and fecal microbiota obtained from mice with PDAC. Time- and inflammatory-dependent stool and pancreatic bacterial composition alterations and stool alpha microbiota diversity reduction were observed only in mice with a Kras mutation that developed advanced pancreatic changes.
View Article and Find Full Text PDFCells
February 2025
Department of Physiology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Lipotoxicity, resulting from the buildup of excess lipids in non-adipose tissues, is increasingly recognized as a major contributor to the progression of kidney disease, highlighting the need for alternative models to assess its effects on renal cells. The main aim of this study was to investigate the usefulness of Caki-1, a human proximal tubule (PT) and renal cell carcinoma (RCC) representative cell line, as a 3D model system for studying free fatty acid-induced PT lipotoxicity. Caki-1 spheroids were generated and maintained on ultra-low attachment plates and characterized regarding time-dependent morphology changes.
View Article and Find Full Text PDFImmunology
March 2025
Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Macrophage apoptosis contributes to acute lung injury (ALI). However, the relationship between cell metabolism and the apoptosis of macrophages remains unclear. In our study, murine alveolar macrophages (MH-S) were stimulated by lipopolysaccharide (LPS) to induce an apoptosis model; cell viability, mitochondrial membrane potential (MMP) and apoptosis rate were determined.
View Article and Find Full Text PDFJ Cosmet Dermatol
March 2025
R&D Innovation Center, Shandong Freda Biotech Co., Ltd., Jinan, Shandong, P. R. China.
Objective: Oxidative stress activates the reactive oxygen species (ROS) and excessive ROS can damage skin cells, initiating oxidative stress responses that contribute to inflammation, aging, and other skin issues. As a resident skin bacterium, Cutibacterium acnes (C. acnes) plays an important role in maintaining skin homeostasis and provides antioxidant benefits.
View Article and Find Full Text PDFCurr Opin Oncol
March 2025
Department of Surgery, Division of Urology.
Purpose Of Review: This review examines the existing literature on metabolic pathways associated with bladder cancer (BC) and investigates four domains: (1) diagnoses, (2) cancer classification (staging & grading), (3) tracking, and (4) treatment.
Recent Findings: A systematic search of relevant databases identified studies meeting predefined inclusion criteria. A diverse array of metabolic pathways was found to hold significant biological and clinical relevance to BC, with particular emphasis on amino acid (AA), lipid, nucleic acid (NA), and bioenergetic pathways.
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