Antimicrobial resistance is a major challenge facing modern medicine, with an estimated 700,000 people dying annually and a global cost in excess of $100 trillion. This has led to an increased need to develop new, effective treatments. This review focuses on nitroimidazoles, which have seen a resurgence in interest due to their broad spectrum of activity against anaerobic Gram-negative and Gram-positive bacteria. The role of nitroreductases is to activate the antimicrobial by reducing the nitro group. A decrease in the activity of nitroreductases is associated with resistance. This review will discuss the resistance mechanisms of different disease organisms, including , and , and how these impact the effectiveness of specific nitroimidazoles. Perspectives in the field of nitroimidazole drug development are also summarised.
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http://dx.doi.org/10.3390/biology10050388 | DOI Listing |
SLAS Technol
December 2024
Department of Medical Oncology, Affiliated Jinling Hospital of Medical School of Nanjing University, Nanjing 210000, PR China. Electronic address:
Nitroreductase (NTR) plays a critical role in the oxygen-deficient environment of anoxic tumor cells, and its identification is crucial for the diagnosis and treatment of cancer. This research introduces an innovative Surface Enhanced Raman Scattering (SERS) probe, created by attaching p-nitrothiophenol (p-NTP) to gold nanoparticles (Au NPs). This probe leverages the specific enzymatic reaction of NTR in hypoxic status, utilizing decreased NADH.
View Article and Find Full Text PDFJ Biol Inorg Chem
December 2024
Department of Chemistry and Biochemistry, University of Wisconsin- Milwaukee, Milwaukee, WI, 53211, USA.
Nitrate reductases play pivotal roles in nitrogen metabolism by leveraging the molybdopterin cofactor to facilitate the reduction of nitrate to nitrite. Periplasmic nitrate reductases (NapA) utilize nitrate as a terminal electron acceptor when oxygen is limiting, helping to drive anaerobic metabolism in bacteria. Despite extensive research into NapA homologs, open questions about the mechanism remain especially at the molecular level.
View Article and Find Full Text PDFJ Phys Chem A
November 2024
Department of Chemistry, Physics & Atmospheric Sciences, Jackson State University, Jackson, Mississippi 39217, United States.
Large-scale implementation of NTO (5-nitro-1,2,4-triazol-3-one), an energetic material used in military applications, causes its discharge to the environment. Reduction of NTO with bacterial nitroreductase or iron-containing minerals results in the formation of ATO (5-amino-1,2,4-triazol-3-one), which is an important intermediate in the process of NTO degradation in the environment. ATO may be dissolved in surface water and groundwater due to its good water solubility.
View Article and Find Full Text PDFNew Phytol
January 2025
Centre for Research in Agricultural Genomics (CRAG), Barcelona, 08193, Spain.
Transcription factors of the CYCLING DOF FACTOR (CDF) family activate in potato the SP6A FT tuberization signal in leaves. In modern cultivars, truncated StCDF1.2 alleles override strict SD control by stabilizing the StCDF1 protein, which leads to StCOL1 suppression and impaired activation of the antagonic SP5G paralog.
View Article and Find Full Text PDFMol Med
October 2024
Laboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine - National Research Institute, 04-141, Warsaw, Poland.
Background: Endometriosis, due to its ambiguous symptoms, still remains one of the most difficult female diseases to treat, with an average diagnosis time of 7-9 years. The changing level of hypoxia plays an important role in a healthy endometrium during menstruation and an elevated expression of the hypoxia-inducible factor 1-alpha (HIF-1α) has been demonstrated in ectopic endometria. HIF-1α mediates the induction of proangiogenic factors and the development of angiogenesis is a critical step in the establishment and pathogenesis of endometriosis.
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