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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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