{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:30:35Z","timestamp":1760059835419,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T00:00:00Z","timestamp":1752451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, Culture, Sports, Science, and Technology (MEXT), Japan","award":["JP20wm0125008","JP223fa627005","22K05999"],"award-info":[{"award-number":["JP20wm0125008","JP223fa627005","22K05999"]}]},{"name":"Japan Agency for Medical Research and Development (AMED)","award":["JP20wm0125008","JP223fa627005","22K05999"],"award-info":[{"award-number":["JP20wm0125008","JP223fa627005","22K05999"]}]},{"name":"JSPS KAKENHI","award":["JP20wm0125008","JP223fa627005","22K05999"],"award-info":[{"award-number":["JP20wm0125008","JP223fa627005","22K05999"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives:\u00a0Mycobacterium avium, a member of Mycobacterium avium complex (MAC), is an emerging opportunistic pathogen causing MAC-pulmonary disease (PD). Fluoroquinolones (FQs), along with ethambutol (EMB) and rifampicin, are recommended for macrolide-resistant MAC-PD; however, FQ-resistant M. avium have been reported worldwide. WQ-3810 is an FQ with high potency against FQ-resistant pathogens; however, its activity against M. avium has not yet been studied. Methods: In this study, we conducted a DNA supercoiling inhibitory assay to evaluate the inhibitory effect of WQ-3810 on recombinant wild-type (WT) and four mutant DNA gyrases of M. avium and compared the IC50s of WQ-3810 with those of ciprofloxacin (CIP), levofloxacin (LVX), and moxifloxacin (MXF). In addition, we examined WQ-3810\u2019s antimicrobial activity against 11 M. avium clinical isolates, including FQ-resistant isolates, with that of other FQs. Furthermore, we assessed the synergistic action of WQ-3810 with the combination of either EMB or isoniazid (INH). Results: In a DNA supercoiling inhibitory assay, WQ-3810 showed 1.8 to 13.7-fold higher efficacy than LVX and CIP. In the MIC assay, WQ-3810 showed 4 to 8-fold, 2 to 16-fold, and 2 to 4-fold higher antimicrobial activity against FQ-resistant isolates than CIP, LVX, and MXF, respectively. The combination of WQ-3810 and INH exhibited a synergistic relationship. Conclusions: The overall characteristics of WQ-3810 demonstrated greater effectiveness than three other FQs, suggesting that it is a promising option for treating FQ-resistant M. avium infections.<\/jats:p>","DOI":"10.3390\/antibiotics14070704","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T11:52:58Z","timestamp":1752580378000},"page":"704","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigation of WQ-3810, a Fluoroquinolone with a High Potential Against Fluoroquinolone-Resistant Mycobacterium avium"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1740-4426","authenticated-orcid":false,"given":"Sasini","family":"Jayaweera","sequence":"first","affiliation":[{"name":"Division of Bioresources, Hokkaido University International Institute for Zoonosis Control, Sapporo 001-0020, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2331-0063","authenticated-orcid":false,"given":"Pondpan","family":"Suwanthada","sequence":"additional","affiliation":[{"name":"Division of Bioresources, Hokkaido University International Institute for Zoonosis Control, Sapporo 001-0020, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1353-5540","authenticated-orcid":false,"given":"David Atomanyi","family":"Barnes","sequence":"additional","affiliation":[{"name":"Division of Bioresources, Hokkaido University International Institute for Zoonosis Control, Sapporo 001-0020, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Poussier","sequence":"additional","affiliation":[{"name":"Division of Bioresources, Hokkaido University International Institute for Zoonosis Control, Sapporo 001-0020, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoyasu","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Keio University Health Center, Yokohama 223-8521, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Keio University School of Medicine, Tokyo 160-8582, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukiko","family":"Nishiuchi","sequence":"additional","affiliation":[{"name":"Toneyama Institute for Tuberculosis Research, Osaka City University Medical School, Toyonaka 560-8552, Japan"},{"name":"Microbial Genomics and Ecology, The IDEC Institute, Hiroshima University, Higashi-Hiroshima 739-8530, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeewan","family":"Thapa","sequence":"additional","affiliation":[{"name":"Division of Bioresources, Hokkaido University International Institute for Zoonosis Control, Sapporo 001-0020, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4833-5542","authenticated-orcid":false,"given":"Stephen V.","family":"Gordon","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, University College Dublin, D04 V1W8 Dublin, Ireland"},{"name":"Institute for Vaccine Research and Development (IVReD), Hokkaido University, Sapporo 001-0021, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7439-5231","authenticated-orcid":false,"given":"Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Bacteriology II, Japan Institute for Health Security (JIHS), Tokyo 208-0011, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chie","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Division of Bioresources, Hokkaido University International Institute for Zoonosis Control, Sapporo 001-0020, Japan"},{"name":"Institute for Vaccine Research and Development (IVReD), Hokkaido University, Sapporo 001-0021, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1313-1494","authenticated-orcid":false,"given":"Yasuhiko","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Division of Bioresources, Hokkaido University International Institute for Zoonosis Control, Sapporo 001-0020, Japan"},{"name":"Institute for Vaccine Research and Development (IVReD), Hokkaido University, Sapporo 001-0021, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mizzi, R., Plain, K.M., Whittington, R., and Timms, V.J. 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