{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T06:08:53Z","timestamp":1782626933341,"version":"3.54.5"},"reference-count":51,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T00:00:00Z","timestamp":1660694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development, AMED","doi-asserted-by":"publisher","award":["JP21fk0108103"],"award-info":[{"award-number":["JP21fk0108103"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>DNA gyrase plays important roles in genome replication in various bacteria, including Pseudomonasaeruginosa. The gyrA gene encodes the gyrase subunit A protein (GyrA). Mutations in GyrA are associated with resistance to quinolone-based antibiotics. We performed a detailed molecular evolutionary analyses of the gyrA gene and associated resistance to the quinolone drug, ciprofloxacin, using bioinformatics techniques. We produced an evolutionary phylogenetic tree using the Bayesian Markov Chain Monte Carlo (MCMC) method. This tree indicated that a common ancestor of the gene was present over 760 years ago, and the offspring formed multiple clusters. Quinolone drug-resistance-associated amino-acid substitutions in GyrA, including T83I and D87N, emerged after the drug was used clinically. These substitutions appeared to be positive selection sites. The molecular affinity between ciprofloxacin and the GyrA protein containing T83I and\/or D87N decreased significantly compared to that between the drug and GyrA protein, with no substitutions. The rate of evolution of the gene before quinolone drugs were first used in the clinic, in 1962, was significantly lower than that after the drug was used. These results suggest that the gyrA gene evolved to permit the bacterium to overcome quinolone treatment.<\/jats:p>","DOI":"10.3390\/microorganisms10081660","type":"journal-article","created":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T22:53:30Z","timestamp":1660776810000},"page":"1660","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Molecular Evolution of the Pseudomonas aeruginosa DNA Gyrase gyrA Gene"],"prefix":"10.3390","volume":"10","author":[{"given":"Mitsuru","family":"Sada","sequence":"first","affiliation":[{"name":"Department of Health Science, Gunma Paz University Graduate School of Health Sciences, Takasaki 370-0006, Gunma, Japan"},{"name":"Advanced Medical Science Research Center, Gunma Paz University Research Institute, Shibukawa 377-0008, Gunma, Japan"},{"name":"Department of Respiratory Medicine, Kyorin University School of Medicine, Mitaka 181-8611, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Health Science, Gunma Paz University Graduate School of Health Sciences, Takasaki 370-0006, Gunma, Japan"},{"name":"Advanced Medical Science Research Center, Gunma Paz University Research Institute, Shibukawa 377-0008, Gunma, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norika","family":"Nagasawa","sequence":"additional","affiliation":[{"name":"Department of Health Science, Gunma Paz University Graduate School of Health Sciences, Takasaki 370-0006, Gunma, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9821-6293","authenticated-orcid":false,"given":"Mao","family":"Akagawa","sequence":"additional","affiliation":[{"name":"Department of Health Science, Gunma Paz University Graduate School of Health Sciences, Takasaki 370-0006, Gunma, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Okayama","sequence":"additional","affiliation":[{"name":"Department of Health Science, Gunma Paz University Graduate School of Health Sciences, Takasaki 370-0006, Gunma, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Shirai","sequence":"additional","affiliation":[{"name":"Advanced Medical Science Research Center, Gunma Paz University Research Institute, Shibukawa 377-0008, Gunma, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soyoka","family":"Sunagawa","sequence":"additional","affiliation":[{"name":"Department of Health Science, Gunma Paz University Graduate School of Health Sciences, Takasaki 370-0006, Gunma, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryusuke","family":"Kimura","sequence":"additional","affiliation":[{"name":"Advanced Medical Science Research Center, Gunma Paz University Research Institute, Shibukawa 377-0008, Gunma, Japan"},{"name":"Department of Bacteriology, Gunma University Graduate School of Medicine, Maebashi 371-8514, Gunma, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0502-8128","authenticated-orcid":false,"given":"Takeshi","family":"Saraya","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Kyorin University School of Medicine, Mitaka 181-8611, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruyuki","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Kyorin University School of Medicine, Mitaka 181-8611, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Kurai","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Kyorin University School of Medicine, Mitaka 181-8611, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7226-3000","authenticated-orcid":false,"given":"Takeshi","family":"Tsugawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Sapporo Medical University School of Medicine, Sapporo 060-8543, Hokkaido, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuyoshi","family":"Nishina","sequence":"additional","affiliation":[{"name":"Department of Applied Chemistry, College of Science and Technology, Nihon University, Chiyoda-ku 101-0062, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruyoshi","family":"Tomita","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, Gunma University Graduate School of Medicine, Maebashi 371-8514, Gunma, 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