Nucleotide metabolism plays a central role in bacterial physiology, producing the nucleic acids necessary for DNA replication and RNA transcription. Recent studies demonstrate that nucleotide metabolism also proactively contributes to antibiotic-induced lethality in bacterial pathogens and that disruptions to nucleotide metabolism contributes to antibiotic treatment failure in the clinic. As antimicrobial resistance continues to grow unchecked, new approaches are needed to study the molecular mechanisms responsible for antibiotic efficacy. Here we review emerging technologies poised to transform understanding into why antibiotics may fail in the clinic. We discuss how these technologies led to the discovery that nucleotide metabolism regulates antibiotic drug responses and why these are relevant to human infections. We highlight opportunities for how studies into nucleotide metabolism may enhance understanding of antibiotic failure mechanisms.
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http://dx.doi.org/10.3389/fdgth.2021.583468 | DOI Listing |
Mikrochim Acta
January 2025
Department of Analytical Chemistry, Faculty of Pharmacy, "Iuliu Hațieganu" University of Medicine and Pharmacy, 4 Pasteur Street, 400349, Cluj-Napoca, Romania.
A label-free, flexible, and disposable aptasensor was designed for the rapid on-site detection of vancomycin (VAN) levels. The electrochemical sensor was based on lab-printed carbon electrodes (C-PE) enriched with cauliflower-shaped gold nanostructures (AuNSs), on which VAN-specific aptamers were immobilized as biorecognition elements and short-chain thiols as blocking agents. The AuNSs, characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM), enhanced the electrochemical properties of the platform and the aptamer immobilization active sites.
View Article and Find Full Text PDFNat Commun
January 2025
Robson DNA Science Centre, Charbonneau Cancer Institute, Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
To tolerate oxidative stress, cells enable DNA repair responses often sensitive to poly(ADP-ribose) (PAR) polymerase 1 and 2 (PARP1/2) inhibition-an intervention effective against cancers lacking BRCA1/2. Here, we demonstrate that mutating the CHD6 chromatin remodeler sensitizes cells to PARP1/2 inhibitors in a manner distinct from BRCA1, and that CHD6 recruitment to DNA damage requires cooperation between PAR- and DNA-binding domains essential for nucleosome sliding activity. CHD6 displays direct PAR-binding, interacts with PARP-1 and other PAR-associated proteins, and combined DNA- and PAR-binding loss eliminates CHD6 relocalization to DNA damage.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Physics and Astronomy, Michigan State University, East Lansing, MI, USA.
DEAD-box RNA-dependent ATPases are ubiquitous in all domains of life where they bind and remodel RNA and RNA-protein complexes. DEAD-box ATPases with helicase activity unwind RNA duplexes by local opening of helical regions without directional movement through the duplexes and some of these enzymes, including Ded1p from Saccharomyces cerevisiae, oligomerize to effectively unwind RNA duplexes. Whether and how DEAD-box helicases coordinate oligomerization and unwinding is not known and it is unclear how many base pairs are actively opened.
View Article and Find Full Text PDFZhonghua Bing Li Xue Za Zhi
February 2025
Department of Pathology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China.
To investigate whether the immunohistochemical results of two markers PMS2 and MSH6 (2-MMR) could replace the four markers MLH1, PMS2, MSH2 and MSH6 (4-MMR) to detect mismatch repair deficient (dMMR) cancers. A retrospective analysis was conducted with summary of immunohistochemical data from 7 867 cases of gastric cancer, colorectal cancer, endometrial cancer, and other diseases in the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China, from March 2018 to March 2023. The consistency of 2-MMR and 4-MMR results was examined.
View Article and Find Full Text PDFAnal Chim Acta
February 2025
Food Inspection and Quarantine Technology Center of Shenzhen Customs, Shenzhen Academy of Inspection and Quarantine, Shenzhen, 518045, PR China.
Background: Ochratoxin A (OTA) is toxic secondary metabolites produced by fungi and can pose a serious threat to food safety and human health. Due to the high stability and toxicity, OTA contamination in agricultural products is of great concern. Therefore, the development of a highly sensitive and reliable OTA detection method is crucial to ensure food safety.
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