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

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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.

Original languageEnglish
Article number294
JournalMolecules
Volume25
Issue number2
Number of pages16
ISSN1420-3049
DOIs
Publication statusPublished - 2 Jan 2020
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 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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