Assaying Chlamydia pneumoniae Persistence in Monocyte-Derived Macrophages Identifies Dibenzocyclooctadiene Lignans as Phenotypic Switchers

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Taavitsainen , E , Kortesoja , M , Bruun , T , Johansson , N G & Hanski , L 2020 , ' Assaying Chlamydia pneumoniae Persistence in Monocyte-Derived Macrophages Identifies Dibenzocyclooctadiene Lignans as Phenotypic Switchers ' , Molecules , vol. 25 , no. 2 , 294 . https://doi.org/10.3390/molecules25020294

Title: Assaying Chlamydia pneumoniae Persistence in Monocyte-Derived Macrophages Identifies Dibenzocyclooctadiene Lignans as Phenotypic Switchers
Author: Taavitsainen, Eveliina; Kortesoja, Maarit; Bruun, Tanja; Johansson, Niklas G; Hanski, Leena
Contributor: University of Helsinki, Division of Pharmaceutical Biosciences
University of Helsinki, Pharmaceutical Design and Discovery group
University of Helsinki, Division of Pharmaceutical Chemistry and Technology
University of Helsinki, Pharmaceutical Design and Discovery group
University of Helsinki, Helsinki One Health (HOH)
Date: 2020-01-02
Language: eng
Number of pages: 16
Belongs to series: Molecules
ISSN: 1420-3049
URI: http://hdl.handle.net/10138/309510
Abstract: Antibiotic-tolerant persister bacteria involve frequent treatment failures, relapsing infections and the need for extended antibiotic treatment. The virulence of an intracellular human pathogen C. pneumoniae is tightly linked to its propensity for persistence and means for its chemosensitization are urgently needed. In the current work, persistence of C. pneumoniae clinical isolate CV6 was studied in THP-1 macrophages using quantitative PCR and quantitative culture. A dibenzocyclooctadiene lignan schisandrin reverted C. pneumoniae persistence and promoted productive infection. The concomitant administration of schisandrin and azithromycin resulted in significantly improved bacterial eradication compared to sole azithromycin treatment. In addition, the closely related lignan schisandrin C was superior to azithromycin in eradicating the C. pneumoniae infection from the macrophages. The observed chemosensitization of C. pneumoniae was associated with the suppression of cellular glutathione pools by the lignans, implying to a previously unknown aspect of chlamydia-host interactions. These data indicate that schisandrin lignans induce a phenotypic switch in C. pneumoniae, promoting the productive and antibiotic-susceptible phenotype instead of persistence. By this means, these medicinal plant -derived compounds show potential as adjuvant therapies for intracellular bacteria resuscitation.
Subject: BACTERIAL PERSISTERS
CELLS
GLUTATHIONE
GROWTH
INHIBIT
OXIDATIVE STRESS
PCR
SCHISANDRIN-B
STATE
adjuvant therapy
antibacterial agent
bacterial persistence
dormancy
glutathione
natural product
3111 Biomedicine
318 Medical biotechnology
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