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doi:10.22028/D291-37165
Titel: | Transferring Microclusters of P. aeruginosa Biofilms to the Air : Liquid Interface of Bronchial Epithelial Cells for Repeated Deposition of Aerosolized Tobramycin |
VerfasserIn: | Horstmann, Justus C. Laric, Annabelle Boese, Annette Yildiz, Daniela Röhrig, Teresa Empting, Martin Frank, Nicolas Krug, Daniel Müller, Rolf Schneider-Daum, Nicole de Souza Carvalho-Wodarz, Cristiane Lehr, Claus-Michael |
Sprache: | Englisch |
Titel: | ACS Infectious Diseases |
Bandnummer: | 8 (2022) |
Heft: | 1 |
Seiten: | 137-149 |
Verlag/Plattform: | ACS |
Erscheinungsjahr: | 2021 |
Freie Schlagwörter: | drug testing inhalation PAO1 metabolomics planktonic bacteria antibiotic |
DDC-Sachgruppe: | 500 Naturwissenschaften 610 Medizin, Gesundheit |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
Abstract: | As an alternative to technically demanding and ethically debatable animal models, the use of organotypic and disease-relevant human cell culture models may improve the throughput, speed, and success rate for the translation of novel anti-infectives into the clinic. Besides bacterial killing, host cell viability and barrier function appear as relevant but seldomly measured readouts. Moreover, bacterial virulence factors and signaling molecules are typically not addressed in current cell culture models. Here, we describe a reproducible protocol for cultivating barrier-forming human bronchial epithelial cell monolayers on Transwell inserts and infecting them with microclusters of pre-grown mature Pseudomonas aeruginosa PAO1 biofilms under the air−liquid interface conditions. Bacterial growth and quorum sensing molecules were determined upon tobramycin treatment. The host cell response was simultaneously assessed through cell viability, epithelial barrier function, and cytokine release. By repeated deposition of aerosolized tobramycin after 1, 24, and 48 h, bacterial growth was controlled (reduction from 10 to 4 log10 CFU/mL), which leads to epithelial cell survival for up to 72 h. E-cadherin’s cell−cell adhesion protein expression was preserved with the consecutive treatment, and quorum sensing molecules were reduced. However, the bacteria could not be eradicated and epithelial barrier function was impaired, similar to the currently observed situation in the clinic in lack of more efficient anti-infective therapies. Such a human-based in vitro approach has the potential for the preclinical development of novel anti-infectives and nanoscale delivery systems for oral inhalation. |
DOI der Erstveröffentlichung: | 10.1021/acsinfecdis.1c00444 |
URL der Erstveröffentlichung: | https://pubs.acs.org/doi/10.1021/acsinfecdis.1c00444 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-371659 hdl:20.500.11880/33723 http://dx.doi.org/10.22028/D291-37165 |
ISSN: | 2373-8227 |
Datum des Eintrags: | 7-Sep-2022 |
Bezeichnung des in Beziehung stehenden Objekts: | Supporting Information |
In Beziehung stehendes Objekt: | https://ndownloader.figstatic.com/files/31910729 |
Fakultät: | M - Medizinische Fakultät NT - Naturwissenschaftlich- Technische Fakultät |
Fachrichtung: | M - Experimentelle und Klinische Pharmakologie und Toxikologie NT - Pharmazie |
Professur: | M - Jun.-Prof. Dr. Daniela Yildiz NT - Prof. Dr. Anna Hirsch NT - Prof. Dr. Claus-Michael Lehr NT - Prof. Dr. Rolf Müller |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
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