{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T05:41:52Z","timestamp":1793252512834,"version":"4.5.0"},"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI21\/01738"],"award-info":[{"award-number":["PI21\/01738"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020907","name":"Instituto Nacional de Salud","doi-asserted-by":"publisher","award":["RO1AI162821"],"award-info":[{"award-number":["RO1AI162821"]}],"id":[{"id":"10.13039\/100020907","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["PID2019-110240RB-I00"],"award-info":[{"award-number":["PID2019-110240RB-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p><jats:italic>Mycobacterium abscessus<\/jats:italic> (MABS) is an emerging pathogen causing severe infections, particularly in cystic fibrosis (CF) patients. A prospective multicentre study included CF patients from four hospitals in Madrid between January 2022 and January 2024. Respiratory samples were collected, and MABS isolates were analysed to determine their antibiotic resistance profiles, growth dynamics, infection kinetics, intracellular behaviour, and pathogenicity. Intracellular bacterial growth and macrophage viability were evaluated through THP-1 cell infection experiments, with and without amikacin. Phenotypic susceptibility testing and genotypic susceptibility testing were also conducted. Among 148 patients, 28 MABS isolates were detected from 16 patients (10.8%), and the first isolate from each patient was analysed. Isolation was more prevalent in younger individuals (median age 24.4 vs. 28.4 years, p\u2009=\u20090.049), and most isolates (81.25%) were identified as <jats:italic>M. abscessus subsp. abscessus<\/jats:italic> (MABSa)<jats:italic>.<\/jats:italic> MABS isolates exhibited high resistance rates (&gt;85%) to doxycycline, tobramycin, ciprofloxacin, moxifloxacin (75%) and cotrimoxazole (56.3%). Amikacin resistance (18.8%) was higher than expected, and inducible (10\/16 isolates) or acquired (1\/16 isolate) macrolide resistance was found in 68.8% of strains. Phenotypic and genotypic testing results were fully concordant. Tigecycline demonstrated strong <jats:italic>in vitro<\/jats:italic> activity, and resistance to imipenem, linezolid, and cefoxitin remained low. Rough strains displayed lower optical density values in later growth stages, probably due to their increased aggregation. In THP-1 cell infection experiments, rough strains showed higher intracellular bacterial loads with statistically significant differences observed at 2 hours (both with and without amikacin) and at 72 hours (with amikacin) post infection. Notably, rough strains also exhibited a higher internalisation index and greater impact on THP-1 cell viability, especially in the absence of amikacin.<\/jats:p>","DOI":"10.1371\/journal.pone.0319710","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T20:20:34Z","timestamp":1743452434000},"page":"e0319710","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Infection model of THP-1 cells, growth dynamics, and antimicrobial susceptibility of clinical Mycobacterium abscessus isolates from cystic fibrosis patients: Results from a multicentre 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An analysis of 154 patients","volume":"147","author":"DE Griffith","year":"1993","journal-title":"Am Rev Respir Dis"},{"issue":"1","key":"pone.0319710.ref033","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1128\/JCM.01249-13","article-title":"Characterization of rough and smooth morphotypes of Mycobacterium abscessus isolates from clinical specimens","volume":"52","author":"K R\u00fcger","year":"2014","journal-title":"J Clin Microbiol"},{"issue":"10","key":"pone.0319710.ref034","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.5588\/ijtld.14.0134","article-title":"Advances in the management of pulmonary disease due to Mycobacterium abscessus complex","volume":"18","author":"W-J Koh","year":"2014","journal-title":"Int J Tuberc Lung Dis"},{"issue":"7","key":"pone.0319710.ref035","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1097\/PAT.0000000000000327","article-title":"Antibiotic susceptibility of diverse Mycobacterium abscessus complex strains in New South Wales, Australia","volume":"47","author":"KYL Chua","year":"2015","journal-title":"Pathology"},{"issue":"1","key":"pone.0319710.ref036","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s12941-023-00637-4","article-title":"Clinical characteristics and drug susceptibility profiles of Mycobacterium abscessus complex infection at a medical school in Thailand","volume":"22","author":"S Sukmongkolchai","year":"2023","journal-title":"Ann Clin Microbiol Antimicrob"},{"issue":"3","key":"pone.0319710.ref037","first-page":"127","article-title":"Molecular characterization of Mycobacterium abscessus subspecies isolated from patients attending an Italian Cystic Fibrosis Centre","volume":"43","author":"A Teri","year":"2020","journal-title":"New Microbiol"},{"issue":"2","key":"pone.0319710.ref038","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.diagmicrobio.2018.08.008","article-title":"Drug susceptibility patterns of Mycobacterium abscessus and Mycobacterium massiliense isolated from respiratory specimens","volume":"93","author":"EH Cho","year":"2019","journal-title":"Diagn Microbiol Infect Dis"},{"key":"pone.0319710.ref039","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.jgar.2021.02.024","article-title":"Antimicrobial susceptibility profiles of Mycobacterium abscessus complex isolates from respiratory specimens in Shanghai, China","volume":"25","author":"Q Guo","year":"2021","journal-title":"J Glob Antimicrob Resist"},{"key":"pone.0319710.ref040","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/1756-0500-5-114","article-title":"Enumeration of Mycobacterium avium subsp. paratuberculosis by quantitative real-time PCR, culture on solid media and optical densitometry","volume":"5","author":"P Kralik","year":"2012","journal-title":"BMC Res Notes"},{"issue":"4","key":"pone.0319710.ref041","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1128\/aem.54.4.910-916.1988","article-title":"A model for analyzing growth kinetics of a slowly growing Mycobacterium sp","volume":"54","author":"RS Lambrecht","year":"1988","journal-title":"Appl Environ Microbiol"},{"issue":"1","key":"pone.0319710.ref042","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1590\/S1517-83822013000100042","article-title":"Measuring of Mycobacterium tuberculosis growth. A correlation of the optical measurements with colony forming units","volume":"44","author":"K Pe\u00f1uelas-Urquides","year":"2013","journal-title":"Braz J Microbiol"},{"issue":"11","key":"pone.0319710.ref043","doi-asserted-by":"crossref","first-page":"160185","DOI":"10.1098\/rsob.160185","article-title":"The distinct fate of smooth and rough Mycobacterium abscessus variants inside macrophages","volume":"6","author":"A-L Roux","year":"2016","journal-title":"Open Biol"},{"issue":"11","key":"pone.0319710.ref044","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1002\/cyto.a.23268","article-title":"A method permissive to fixation and permeabilization for the multiparametric analysis of apoptotic and necrotic cell phenotype by flow cytometry","volume":"91","author":"S Mariotti","year":"2017","journal-title":"Cytometry A"},{"key":"pone.0319710.ref045","doi-asserted-by":"crossref","unstructured":"Pichler V, Dalkilic L, Shoaib G, Shapira T, Rankine-Wilson L, Boudehen Y-M, et al. 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