Effects of the order of exposure to antimicrobials on the incidence of multidrug-resistant Pseudomonas aeruginosa
Abstract Multidrug-resistant Pseudomonas aeruginosa (MDRP) is one of the most important pathogens in clinical practice. To clarify the mechanisms contributing to its emergence, we isolated MDRPs using the P. aeruginosa PAO1, the whole genome sequence of which has already been elucidated. Mutant stra...
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| Format: | Article |
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Nature Portfolio
2023-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-35256-8 |
| _version_ | 1831516793861046272 |
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| author | Nami Yasuda Tomoko Fujita Takahiro Fujioka Mei Tagawa Naoki Kohira Kensho Torimaru Sumiko Shiota Takanori Kumagai Daichi Morita Wakano Ogawa Tomofusa Tsuchiya Teruo Kuroda |
| author_facet | Nami Yasuda Tomoko Fujita Takahiro Fujioka Mei Tagawa Naoki Kohira Kensho Torimaru Sumiko Shiota Takanori Kumagai Daichi Morita Wakano Ogawa Tomofusa Tsuchiya Teruo Kuroda |
| author_sort | Nami Yasuda |
| collection | DOAJ |
| description | Abstract Multidrug-resistant Pseudomonas aeruginosa (MDRP) is one of the most important pathogens in clinical practice. To clarify the mechanisms contributing to its emergence, we isolated MDRPs using the P. aeruginosa PAO1, the whole genome sequence of which has already been elucidated. Mutant strains resistant to carbapenems, aminoglycosides, and new quinolones, which are used to treat P. aeruginosa infections, were isolated; however, none met the criteria for MDRPs. Then, PAO1 strains were exposed to these antimicrobial agents in various orders and the appearance rate of MDRP varied depending on the order of exposure; MDRPs more frequently appeared when gentamicin was applied before ciprofloxacin, but were rarely isolated when ciprofloxacin was applied first. Exposure to ciprofloxacin followed by gentamicin increased the expression of MexCD-OprJ, an RND-type multidrug efflux pump, due to the NfxB mutation. In contrast, exposure to gentamicin followed by ciprofloxacin resulted in more mutations in DNA gyrase. These results suggest that the type of quinolone resistance mechanism is related to the frequency of MDRP and that the risk of MDRP incidence is highly dependent on the order of exposure to gentamicin and ciprofloxacin. |
| first_indexed | 2024-03-13T07:24:29Z |
| format | Article |
| id | doaj.art-8c6cc076f38940e080b687e7b1942031 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-13T07:24:29Z |
| publishDate | 2023-05-01 |
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| series | Scientific Reports |
| spelling | doaj.art-8c6cc076f38940e080b687e7b19420312023-06-04T11:26:32ZengNature PortfolioScientific Reports2045-23222023-05-011311910.1038/s41598-023-35256-8Effects of the order of exposure to antimicrobials on the incidence of multidrug-resistant Pseudomonas aeruginosaNami Yasuda0Tomoko Fujita1Takahiro Fujioka2Mei Tagawa3Naoki Kohira4Kensho Torimaru5Sumiko Shiota6Takanori Kumagai7Daichi Morita8Wakano Ogawa9Tomofusa Tsuchiya10Teruo Kuroda11Department of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Microbiology, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Molecular Biology, School of Pharmacy, Shujitsu UniversityDepartment of Microbiology, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAbstract Multidrug-resistant Pseudomonas aeruginosa (MDRP) is one of the most important pathogens in clinical practice. To clarify the mechanisms contributing to its emergence, we isolated MDRPs using the P. aeruginosa PAO1, the whole genome sequence of which has already been elucidated. Mutant strains resistant to carbapenems, aminoglycosides, and new quinolones, which are used to treat P. aeruginosa infections, were isolated; however, none met the criteria for MDRPs. Then, PAO1 strains were exposed to these antimicrobial agents in various orders and the appearance rate of MDRP varied depending on the order of exposure; MDRPs more frequently appeared when gentamicin was applied before ciprofloxacin, but were rarely isolated when ciprofloxacin was applied first. Exposure to ciprofloxacin followed by gentamicin increased the expression of MexCD-OprJ, an RND-type multidrug efflux pump, due to the NfxB mutation. In contrast, exposure to gentamicin followed by ciprofloxacin resulted in more mutations in DNA gyrase. These results suggest that the type of quinolone resistance mechanism is related to the frequency of MDRP and that the risk of MDRP incidence is highly dependent on the order of exposure to gentamicin and ciprofloxacin.https://doi.org/10.1038/s41598-023-35256-8 |
| spellingShingle | Nami Yasuda Tomoko Fujita Takahiro Fujioka Mei Tagawa Naoki Kohira Kensho Torimaru Sumiko Shiota Takanori Kumagai Daichi Morita Wakano Ogawa Tomofusa Tsuchiya Teruo Kuroda Effects of the order of exposure to antimicrobials on the incidence of multidrug-resistant Pseudomonas aeruginosa Scientific Reports |
| title | Effects of the order of exposure to antimicrobials on the incidence of multidrug-resistant Pseudomonas aeruginosa |
| title_full | Effects of the order of exposure to antimicrobials on the incidence of multidrug-resistant Pseudomonas aeruginosa |
| title_fullStr | Effects of the order of exposure to antimicrobials on the incidence of multidrug-resistant Pseudomonas aeruginosa |
| title_full_unstemmed | Effects of the order of exposure to antimicrobials on the incidence of multidrug-resistant Pseudomonas aeruginosa |
| title_short | Effects of the order of exposure to antimicrobials on the incidence of multidrug-resistant Pseudomonas aeruginosa |
| title_sort | effects of the order of exposure to antimicrobials on the incidence of multidrug resistant pseudomonas aeruginosa |
| url | https://doi.org/10.1038/s41598-023-35256-8 |
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