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PprA, a radiation-induced Deinococcus-specific protein, was previously shown to be required for cell survival and accurate chromosome segregation after exposure to ionizing radiation. Here, we used an in vivo approach to determine, by shotgun proteomics, putative PprA partners coimmunoprecipitating with PprA when cells were exposed to gamma rays. Among them, we found the two subunits of DNA gyrase and, thus, chose to focus our work on characterizing the activities of the deinococcal DNA gyrase in the presence or absence of PprA. Loss of PprA rendered cells hypersensitive to novobiocin, an inhibitor of the B subunit of DNA gyrase. We showed that treatment of bacteria with novobiocin resulted in induction of the radiation desiccation response (RDR) regulon and in defects in chromosome segregation that were aggravated by the absence of PprA. In vitro, the deinococcal DNA gyrase, like other bacterial DNA gyrases, possesses DNA negative supercoiling and decatenation activities. These two activities are inhibited in vitro by novobiocin and nalidixic acid, whereas PprA specifically stimulates the decatenation activity of DNA gyrase. Together, these results suggest that PprA plays a major role in chromosome decatenation via its interaction with the deinococcal DNA gyrase when D. radiodurans cells are recovering from exposure to ionizing radiation. IMPORTANCE D. radiodurans is one of the most radiation-resistant organisms known. This bacterium is able to cope with high levels of DNA lesions generated by exposure to extreme doses of ionizing radiation and to reconstruct a functional genome from hundreds of radiation-induced chromosomal fragments. Here, we identified partners of PprA, a radiation-induced Deinococcus-specific protein, previously shown to be required for radioresistance. Our study leads to three main findings: (i) PprA interacts with DNA gyrase after irradiation, (ii) treatment of cells with novobiocin results in defects in chromosome segregation that are aggravated by the absence of PprA, and (iii) PprA stimulates the decatenation activity of DNA gyrase. Our results extend the knowledge of how D. radiodurans cells survive exposure to extreme doses of gamma irradiation and point out the link between DNA repair, chromosome segregation, and DNA gyrase activities in the radioresistant D. radiodurans bacterium.
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http://dx.doi.org/10.1128/mSphere.00036-15 | DOI Listing |
PLoS Genet
September 2025
Dept of Biology, Portland State University, Portland, Oregon, United States of America.
The ability to complete DNA replication as replisomes converge has recently been shown to be a highly-regulated, multi-enzymatic process. Converging forks also are likely to generate unique supercoiled, tangled, or knotted substrates. These structures are typically resolved by one of the four topoisomerases encoded by Escherichia coli.
View Article and Find Full Text PDFArch Microbiol
September 2025
Medical and Biological Computing Laboratory, School of Biosciences and Technology (SBST), Vellore Institute of Technology (VIT), Vellore, 632014, India.
Salmonella enterica serovar Typhi, the etiological agent of Typhoid fever, remains a critical public health concern associated with high morbidity in many developing countries. The widespread emergence of multidrug-resistant (MDR) Salmonella Typhi strains against the fluoroquinolone group of antibiotics, particularly ciprofloxacin, poses a significant global therapeutic challenge with underlying resistance due to mutations in quinolone-resistance determining region (QRDR) of gyrA gene, encoding DNA gyrase subunit A (GyrA). In pursuit of alternative therapeutic candidates, the present study was designed to evaluate ciprofloxacin analogues against prevalent GyrA mutations (S83F, D87G, and D87N) to overcome fluoroquinolone resistance through machine learning (ML)-based approach.
View Article and Find Full Text PDFRSC Adv
August 2025
Department of Chemistry, Research Centre HPT Arts and RYK Science College (Affiliated to S. P. Pune University) Nashik Maharashtra 422005 India
The persistent threat of pathogenic microorganisms demands the development of innovative scaffolds with dual antibacterial and antifungal activities. Herein, we report the synthesis and characterization of a novel series of benzothiazole-thiazole hybrids (4a-4f) a three-step route, confirmed by NMR and MS analyses. The compounds were screened against Gram-positive, Gram-negative, mycobacterial, and fungal strains using disk diffusion and REMA assays.
View Article and Find Full Text PDFCarbohydr Polym
November 2025
Polymer Institute of the Slovak Academy of Sciences, Dúbravská Cesta 9, 845 41 Bratislava, Slovakia; Polymer Materials Research Department, Advanced Technology and New Materials Research Institute (ATNMRI), City of Scientific Research and Technological Applications (SRTA-City), New Borg El-Arab Ci
This study involves the synthesis of a novel 7-ethoxy-3-formyl-2-morpholino quinoline (MQ) derivative, which was hybridized with aminated chitosan (AMCH) to yield a new AMCH-MQ Schiff base. Structural characterization via H NMR, FTIR, electronic spectra, XRD, and TGA confirmed successful hybridization. Ion exchange capacity decreased from 28.
View Article and Find Full Text PDFBioorg Chem
August 2025
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China. Electronic address:
This work developed a class of unique benzopyronyl imidazolidinediones (BIs) as new structural skeleton of potential multitargeting antibacterial agents to confront dreadful Staphylococcus aureus infections. Some target compounds exhibited effective antibacterial activities against the tested strains. Especially, butyl BI 6c and 5-hydroxy BI 26d exerted excellent inhibitory activity toward Staphylococcus aureus ATCC 25923 and MRSA 43300 with a low MIC value of 0.
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