Objectives: The aim of this study was to identify the synergistic effect and mechanisms of fosfomycin (FM) combined with colistin (COL) against KPC-producing Klebsiella pneumoniae (KPC-Kp).
Methods: The bactericidal effects, induced drug resistance and cytotoxicity of FM combined with COL were evaluated by time-kill assays and mutation rate test. Time-kill assays and transcriptomics analysis were used to further clarify the mechanism of FM combined with COL. The bacteria were taken from different points in time-kill assays, reactive oxygen species (ROS), nitric oxide and redox related enzymes were detected. The mechanism of synergistic bactericidal action was analyzed by transcriptome.
Results: The bactericidal effect of FM combined with COL was better than that of monotherapy. The mutation frequency of FM alone at low dose (8 mg/L) was higher than that at high dose (64 mg/L). COL induced resistant isolates resulted in FM and COL resistance, while FM alone or combined with COL only resulted in FM resistance. The survival rate of Thp-1 cells in FM combined with COL against K. pneumoniae was higher than that of monotherapy. The intracellular nitric oxide, activities of total superoxide dismutase and catalase were increased along with the increase of FM concentration against KPC-Kp. FM combined with COL induced ROS accumulation and antioxidant capacity increase. Transcriptome analysis showed FM combined with COL could regulate the levels of soxRS and oxidative phosphorylation, in order to clear ROS and repair damage. In addition, FM combined with COL could result in synergetic bactericidal efficacy by inhibiting ribosomal transcription.
Conclusions: FM combined with COL mediated synergistic bactericidal effect by regulating ROS accumulation and inhibiting ribosomal protein transcription, resulting in lower resistance and cytotoxicity.
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http://dx.doi.org/10.1186/s12866-024-03581-1 | DOI Listing |
Regen Biomater
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Orthopedics and Sports Medicine Center, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou 215008, P. R. China.
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View Article and Find Full Text PDFJ Cell Physiol
January 2025
Department of Biosciences & Bioengineering, IIT Bombay, Mumbai, India.
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View Article and Find Full Text PDFFood Technol Biotechnol
December 2024
National Technological Institute of Mexico / Technological Institute of Tepic, Av. Tecnológico 2595, Col. Lagos del Country, C.P. 63175, Tepic, Nayarit, Mexico.
Plant-based beverages are water-soluble extracts of cereals, pseudocereals, seeds and legumes that resemble milk in appearance. However, these products have important differences compared to normal liquid milk, such as nutritional composition, sensorial properties and shelf-life stability. Increasing number of consumers are opting for these beverages due to lactose intolerance, milk protein allergies or lifestyle.
View Article and Find Full Text PDFJ Mol Model
January 2025
Escuela Superior de Física y Matemáticas, IPN S/N, Edificio 9 de la Unidad Profesional "Adolfo López Mateos", Col. Lindavista, Alc. Gustavo A. Madero, 07738, Mexico City, Mexico.
Context: "Nanostructure of graphene-reinforced with polymethyl methacrylate" (PMMA-G), and vice versa, is investigated using its molecular structure, in the present work. The PMMA-G nanostructure was constructed by bonding PMMA with graphene nanosheet in a sense to get three different configurations. Each configuration consisted of polymeric structures with three degrees of polymerization (such as monomers, dimers, and trimers polymers, respectively).
View Article and Find Full Text PDFInt J Med Mushrooms
January 2025
Infectious Diseases Research Center, National Institute of Public Health.
Fungi have proved to be useful sources of compounds with antineoplastic properties. Although several metabolites isolated from species of the genus Omphalotus have shown cytotoxic effects on tumor cell lines. Few works have studied Omphalotus nidiformis.
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