{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T14:22:51Z","timestamp":1780410171250,"version":"3.54.1"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Due to the inherent drug-resistance mechanisms and biofilm formation of\n                      <jats:italic>Mycobacterium<\/jats:italic>\n                      abscessus (\n                      <jats:italic>Mab<\/jats:italic>\n                      ) that attenuate drug sensitivity, characterizing the impact of these factors on the pharmacological profile of antibiotics is critical to improve therapeutic outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study aimed to define the exposure-response relationship of tigecycline in\n                      <jats:italic>Mab<\/jats:italic>\n                      therapy and to simultaneously evaluate the effects of biofilm and resistance development on bacterial killing activity of tigecycline using a Transwell system and a Hollow Fiber Infection Model combined with pharmacokinetic\/pharmacodynamic (PK\/PD) modeling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Dynamic time-kill assays conducted using the hollow fiber system, which mimicked tigecycline lung exposure under diverse intrapulmonary aerosol administration scenarios, demonstrated that high exposure to tigecycline effectively killed\n                      <jats:italic>Mab<\/jats:italic>\n                      . However, the pattern and timing of bacterial resistance development varied depending on the dosing regimen when exposure was insufficient for complete bacterial killing. Transwell-based\n                      <jats:italic>in vitro<\/jats:italic>\n                      tigecycline permeability study results revealed that the biofilm played a crucial role as a barrier to prevent molecular transfer of drug, eventually reducing the extent of exposure to\n                      <jats:italic>Mab<\/jats:italic>\n                      in biofilm by generating concentration gradients. The PK\/PD model, integrating data from the\n                      <jats:italic>in vitro<\/jats:italic>\n                      dynamic time-kill assay and biofilm permeability study, adequately captured multiple factors, including dose-dependent bacterial killing, transition of\n                      <jats:italic>Mab<\/jats:italic>\n                      to less susceptible populations, biofilm formation, and biofilm-associated changes in permeability, all of which can influence the antibacterial activity of tigecycline.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      A quantitative assessment of the impact of these factors modulating the bacterial pathophysiology provides insights into how\n                      <jats:italic>Mab<\/jats:italic>\n                      undermines the antibacterial efficacy of tigecycline, thereby ultimately contributing to the development of more efficacious tigecycline treatment strategies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1799565","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T05:39:16Z","timestamp":1777354756000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of biofilm formation on the antimicrobial activity of tigecycline against Mycobacterium abscessus in the hollow fiber infection model"],"prefix":"10.3389","volume":"17","author":[{"given":"Hyunseo","family":"Park","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center","place":["Memphis, TN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara E.","family":"Maloney Norcross","sequence":"additional","affiliation":[{"name":"Engineering and Advanced Technology Department, RTI International","place":["Durham, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Hickey","sequence":"additional","affiliation":[{"name":"Engineering and Advanced Technology Department, RTI International","place":["Durham, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Gonzalez-Juarrero","sequence":"additional","affiliation":[{"name":"Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University","place":["Fort Collins, CO, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Meibohm","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center","place":["Memphis, TN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e0241524","DOI":"10.1128\/spectrum.02415-24","article-title":"Heme alters biofilm formation in Mycobacterium abscessus.","volume":"13","author":"Aftab","year":"2025","journal-title":"Microbiol Spectr"},{"key":"B2","unstructured":"Baron\n              K. 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