AP-1 transcription factor serves as a molecular switch between Chlamydia pneumoniae replication and Persistence

S. Krämer, P. Crauwels, R. Bohn, C. Radzimski, M. Szaszák, M. Klinger, J. Rupp, G. van Zandbergen*

*Corresponding author for this work
1 Citation (Scopus)

Abstract

Chlamydia pneumoniae is a Gram-negative bacterium that causes acute or chronic respiratory infections. As obligate intracellular pathogens, chlamydiae efficiently manipulate host cell processes to ensure their intracellular development. Here we focused on the interaction of chlamydiae with the host cell transcription factor activator protein 1 (AP-1) and its consequence on chlamydial development. During Chlamydia pneumoniae infection, the expression and activity of AP-1 family proteins c-Jun, c-Fos, and ATF-2 were regulated in a time- and dose-dependent manner. We observed that the c-Jun protein and its phosphorylation level significantly increased during C. pneumoniae development. Small interfering RNA knockdown of the c-Jun protein in HEp-2 cells reduced the chlamydial load, resulting in smaller inclusions and significantly lower chlamydial recovery. Furthermore, inhibition of the c-Jun-containing AP-1 complexes using tanshinone IIA changed the replicative infection phenotype into a persistent one. Tanshinone IIA-dependent persistence was characterized by smaller, aberrant inclusions, a strong decrease in the chlamydial load, and significantly reduced chlamydial recovery, as well as by the reversibility of the reduced recovery after the removal of tanshinone IIA. Interestingly, not only was tanshinone IIA treatment accompanied by a significant decrease of ATP levels, but fluorescence live cell imaging analysis by two-photon microscopy revealed that tanshinone IIA treatment also resulted in a decreased fluorescence lifetime of protein-bound NAD(P)H inside the chlamydial inclusion, indicating that chlamydial reticulate bodies have decreased metabolic activity. In all, these data demonstrate that the AP-1 transcription factor is involved in C. pneumoniae development, with tanshinone IIA treatment resulting in persistence.

Original languageEnglish
JournalInfection and Immunity
Volume83
Issue number7
Pages (from-to)2651-2660
Number of pages10
ISSN0019-9567
DOIs
Publication statusPublished - 01.01.2015

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)

Fingerprint

Dive into the research topics of 'AP-1 transcription factor serves as a molecular switch between Chlamydia pneumoniae replication and Persistence'. Together they form a unique fingerprint.

Cite this