{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:05:46Z","timestamp":1760058346136,"version":"build-2065373602"},"reference-count":96,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>This study examines the impact of inhaled tobramycin therapy on the within-host changes in P. aeruginosa strains isolated from Bulgarian patients with CF prior to and post treatment. Genotypic comparison by RAPD-PCR indicated that most of the pre-treatment isolates had a high similarity and were genetically comparatively close to strains from other countries with known increased morbidity or treatment requirements. Most of the post-treatment isolates were, however, genetically distant from their pre-treatment counterparts, showing genotypic diversification after the treatment. Phenotypic comparisons showed a lower ODmax reached during groswth and an increased lag-time in the post-treatment isolates. All strains were capable of invasion and intracellular reproduction within A549 cultured cells. The addition of sub-inhibitory amounts (1\/4 or 1\/2 MIC) of tobramycin during growth showed the higher relative fitness (as a percentage of the untreated control) of the post-treatment strains. The effects of sub-MICs on biofilm growth did not show such a pronounced trend. However, when a resazurin-based viability test was applied, the advantage of the post-treatment strains was confirmed for both broth and biofilm cultures. In spite of that, according to the determined MIC values, all isolates were tobramycin-sensitive, and the data from this study imply the development of tolerance to the antibiotic in the strains that survived the treatment.<\/jats:p>","DOI":"10.3390\/microorganisms13040730","type":"journal-article","created":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T10:53:54Z","timestamp":1742900034000},"page":"730","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Diversification of Pseudomonas aeruginosa After Inhaled Tobramycin Therapy of Cystic Fibrosis Patients: Genotypic and Phenotypic Characteristics of Paired Pre- and Post-Treatment Isolates"],"prefix":"10.3390","volume":"13","author":[{"given":"Dayana","family":"Borisova","sequence":"first","affiliation":[{"name":"The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 25, 1113 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5197-1849","authenticated-orcid":false,"given":"Tanya","family":"Strateva","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology \u201cCorr. Mem. Prof. Ivan Mitov, MD, DMSc\u201d, Faculty of Medicine, Medical University of Sofia, 2 Zdrave Str., 1431 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2564-2427","authenticated-orcid":false,"given":"Svetoslav G.","family":"Dimov","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Sofia University \u201cSt. Kliment Ohridski\u201d, 8 Dragan Tsankov Blvd., 1164 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Borjana","family":"Atanassova","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Sofia University \u201cSt. Kliment Ohridski\u201d, 8 Dragan Tsankov Blvd., 1164 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8376-8917","authenticated-orcid":false,"given":"Tsvetelina","family":"Paunova-Krasteva","sequence":"additional","affiliation":[{"name":"The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Acad. 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