Molecular Characterization and Mutational Analysis of Clarithromycin- and Levofloxacin-Resistance Genes in Helicobacter pylori from Gastric Biopsies in Southern Croatia
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Published:2023-09-26
Issue:19
Volume:24
Page:14560
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Šamanić Ivica1ORCID, Dadić Blanka1, Sanader Maršić Željka2ORCID, Dželalija Mia1ORCID, Maravić Ana1, Kalinić Hrvoje3, Vrebalov Cindro Pavle4, Šundov Željko45, Tonkić Marija6, Tonkić Ante45, Vuković Jonatan45
Affiliation:
1. Department of Biology, Faculty of Science, University of Split, Ruđera Boškovića 33, 21000 Split, Croatia 2. Department of Physics, Faculty of Science, University of Split, Ruđera Boškovića 33, 21000 Split, Croatia 3. Department of Compute Science, Faculty of Science, University of Split, Ruđera Boškovića 33, 21000 Split, Croatia 4. Department of Gastroenterology, University Hospital of Split, 21000 Split, Croatia 5. Department of Internal Medicine, School of Medicine, University of Split, 21000 Split, Croatia 6. Department of Medical Microbiology and Parasitology, School of Medicine, University of Split, 21000 Split, Croatia
Abstract
Point mutations in the 23S rRNA, gyrA, and gyrB genes can confer resistance to clarithromycin (CAM) and levofloxacin (LVX) by altering target sites or protein structure, thereby reducing the efficacy of standard antibiotics in the treatment of Helicobacter pylori infections. Considering the confirmed primary CAM and LVX resistance in H. pylori infected patients from southern Croatia, we performed a molecular genetic analysis of three target genes (23S rRNA, gyrA, and gyrB) by PCR and sequencing, together with computational molecular docking analysis. In the CAM-resistant isolates, the mutation sites in the 23S rRNA gene were A2142C, A2142G, and A2143G. In addition, the mutations D91G and D91N in GyrA and N481E and R484K in GyrB were associated with resistance to LVX. Molecular docking analyses revealed that mutant H. pylori strains with resistance-related mutations exhibited a lower susceptibility to CAM and LVX compared with wild-type strains due to significant differences in non-covalent interactions (e.g., hydrogen bonds, ionic interactions) leading to destabilized antibiotic–protein binding, ultimately resulting in antibiotic resistance. Dual resistance to CAM and LVX was found, indicating the successful evolution of H. pylori resistance to unrelated antimicrobials and thus an increased risk to human health.
Funder
annual funds for institutional financing of scientific activities of the Ministry of Science and Education of the Republic of Croatia
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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