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“Effect of Subinhibitory Concentrations of Some Antibiotics and Low Doses of Gamma Radiation on the Cytotoxicity and Expression of Colibactin by an Uropathogenic Escherichia coli isolate”

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Abstract

Colibactin and cytotoxic necrotizing factor 1 (Cnf 1) are cyclomodulins secreted by uropathogenic E. coli. In this study, uropathogenic E. coli expressing colibactin and Cnf 1 was exposed to antibiotics subMICs and gamma radiation to investigate their effects on its cytotoxicity and expression of colibactin. The test isolate was exposed to three subMIC levels of levofloxacin, ciprofloxacin, trimethoprim/sulfamethoxazole and ceftriaxone and irradiated with gamma rays at 10 and 24.4 Gy. The cytotoxicity for either antibiotic or gamma rays treated cultures was measured using MTT assay and the expression of colibactin encoding genes was determined by RT-PCR. Treatment with fluoroquinolones nearly abolished the cytotoxicity of E. coli isolate and significantly downregulated clbA gene expression at the tested subMICs (P ≤ 0.05) while trimethoprim/sulfamethoxazole treated cultures exerted significant downregulation of clbA and clbQ genes at 0.5 MIC only (P ≤ 0.05). Ceftriaxone treated cultured exhibited reduction in the cytotoxicity and insignificant effects on expression of clbA, clbQ and clbM genes. On contrast, significant upregulation in the expression of clbA and clbQ genes was observed in irradiated cultures (P ≤ 0.05). Fluoroquinolones reduced both the cytotoxicity of UPEC isolate and colibactin expression at different subMICs while ceftriaxone at subMICs failed to suppress the expression of genotoxin, colibactin, giving an insight to the risks associated upon their choice for UTI treatment. Colibactin expression was enhanced by gamma irradiation at doses resembling these received during pelvic radiotherapy which might contribute to post-radiotherapy complications.

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Authors and Affiliations

  1. National Centre for Radiation Research and Technology (NCRRT), Drug Radiation Research Department, Egyptian Atomic Energy Authority (EAEA), Ahmed El-Zomor Street, Nasr city, Cairo, 11787, Egypt

    Radwa N. Morgan & Hala A. Farrag

  2. Microbiology and Immunology Department, Faculty of Pharmacy, Ain Shams University, African union organization Street, Abbassia, Cairo, 11566, Egypt

    Mohammad M. Aboulwafa & Sarra E. Saleh

  3. Faculty of Pharmacy, King Salman International University, South Sinai, Ras-Sedr, Egypt

    Mohammad M. Aboulwafa

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  1. Radwa N. Morgan
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All authors contributed in the study conception and design equally. RM, conducted the practical work and collected the results, SS, supervised the practical work, HF, revised the first draft of the manuscript and MA revised the final version of the manuscript and produced in its final form. All authors have read and approved the final form of the manuscript. All Authors follow the ICMJE criteria.

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Morgan, R.N., Farrag, H.A., Aboulwafa, M.M. et al. “Effect of Subinhibitory Concentrations of Some Antibiotics and Low Doses of Gamma Radiation on the Cytotoxicity and Expression of Colibactin by an Uropathogenic Escherichia coli isolate”. Curr Microbiol 78, 544–557 (2021). https://doi.org/10.1007/s00284-020-02331-6

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